MELANOCYTIC NEVI (NORMAL MOLES)
In general, a benign mole is a small (less than 6 mm) macule or papule with a well-defined border and homogeneous beige or pink to dark brown pigment (eFigure 6–3). They represent benign melanocytic growths.
Normal mole (nevus). (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Moles have a typical natural history. Early in life, moles often appear as flat, small, brown lesions and are termed “junctional nevi” because the nevus cells are at the junction of the epidermis and dermis. Over time, these moles enlarge and often become raised, reflecting the appearance of a dermal component, giving rise to compound nevi (Figure 6–1). Moles may darken and grow during pregnancy. As white patients enter their eighth decade, most moles have lost their junctional component and dark pigmentation. At every stage of life, normal moles should be well demarcated, symmetric, and uniform in contour and color. Regular mole screening is not an evidence-based recommendation for all adults although rates of screening continue to rise.
Benign, flat and macular compound nevus on the arm. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
et al. Delivering value in dermatology: insights from skin cancer detection in routine clinical visits. J Am Acad Dermatol. 2015 Feb;72(2):310–3.
et al. Total body skin examination for skin cancer screening among U.S. adults from 2000 to 2010. Prev Med. 2014 Apr;61:75–80.
et al. Screening, early detection, education, and trends for melanoma: current status (2007–2013) and future directions: Part I. Epidemiology, high-risk groups, clinical strategies, and diagnostic technology. J Am Acad Dermatol. 2014 Oct;71(4):599.e1–599.e12.
et al. Screening, early detection, education, and trends for melanoma: current status (2007–2013) and future directions: Part II. Screening, education, and future directions. J Am Acad Dermatol. 2014 Oct;71(4):611.e1–611.e10.
et al. Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. Br J Dermatol. 2015 Jan;172(1):33–47.
The term “atypical nevus” or “atypical mole” has supplanted “dysplastic nevus.” The diagnosis of atypical moles is made clinically and not histologically, and moles should be removed only if they are suspected to be melanomas. Dermoscopy by a trained clinician may be a useful tool in the evaluation of atypical nevi. Clinically, these moles are large (6 mm or more in diameter), with an ill-defined, irregular border and irregularly distributed pigmentation (Figure 6–2) (eFigure 6–4). It is estimated that 5–10% of the white population in the United States has one or more atypical nevi, and recreational sun exposure is a primary risk for the development of atypical nevi in nonfamilial settings. Studies have defined an increased risk of melanoma in the following populations: patients with 50 or more nevi with one or more atypical moles and one mole at least 8 mm or larger, and patients with any number of definitely atypical moles. These patients should be educated in how to recognize changes in moles and be monitored regularly (every 6–12 months) by a clinician. Kindreds with familial melanoma (numerous atypical nevi and a family history of two first-degree relatives with melanoma) deserve even closer attention, as the risk of developing single or even multiple melanomas in these individuals approaches 50% by age 50.
Atypical (dysplastic) nevus on the chest. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Atypical mole (nevus). (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
et al. The dysplastic nevus: from historical perspective to management in the modern era: part I. Historical, histologic, and clinical aspects. J Am Acad Dermatol. 2012 Jul;67 (1):1.e1–16.
et al. The dysplastic nevus: from historical perspective to management in the modern era: part II. Molecular aspects and clinical management. J Am Acad Dermatol. 2012 Jul;67(1):19.e1–12.
et al. Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement. JAMA Dermatol. 2015 Feb 1;151(2):212–8.
et al. Dermoscopy for the family physician. Am Fam Physician. 2013 Oct 1;88(7):441–50.
Blue nevi are small, slightly elevated, blue-black lesions (Figure 6–3) that favor the dorsal hands. They are common in persons of Asian descent, and an individual patient may have several of them. If the lesion has remained unchanged for years, it may be considered benign, since malignant blue nevi are rare. However, blue-black papules and nodules that are new or growing must be evaluated to rule out nodular melanoma.
Blue nevus on the left cheek, with some resemblance to a melanoma. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
et al. Acquired blue nevi in older individuals: retrospective case series from a Veterans Affairs population, 1991 to 2013. JAMA Dermatol. 2014 Aug;150(8):873–6.
Freckles (ephelides) and lentigines are flat brown macules, typically between 3 mm and 5 mm in diameter (eFigure 6–5) (eFigure 6–6). Freckles first appear in young children, darken with ultraviolet exposure, and fade with cessation of sun exposure. They are determined by genetic factors. In adults, lentigines gradually appear in sun-exposed areas, particularly the face, dorsal hands, upper back, and upper chest, starting in the fourth to fifth decade of life, and are associated with photoaging as well as estrogen and progesterone use. On the upper back, they may have a very irregular border (inkspot lentigines). They do not fade with cessation of sun exposure. They should be evaluated like all pigmented lesions: if the pigmentation is homogeneous and they are symmetric and flat, they are most likely benign. They can be treated with topical 0.1% tretinoin, 0.1% tazarotene, 2% 4-hydroxyanisole with 0.01% tretinoin, hydroquinone laser/light therapy, or cryotherapy.
Lentigo simplex (mole on white skin). (Used, with permission, from S Goldstein.)
Lentigo simplex (hyperpigmented area on female's face). (Used, with permission, from S Goldstein.)
et al. Triple combination as adjuvant to cryotherapy in the treatment of solar lentigines: investigator-blinded, randomized clinical trial. J Eur Acad Dermatol Venereol. 2015 Jan;29(1):128–33.
et al. Sun-induced freckling: ephelides and solar lentigines. Pigment Cell Melanoma Res. 2014 May;27(3):339–50.
Seborrheic keratoses are benign papules and plaques, beige to brown or even black, 3–20 mm in diameter, with a velvety or warty surface (Figure 6–4) (eFigure 6–7). They appear to be stuck or pasted onto the skin. They are extremely common—especially in the elderly—and may be mistaken for melanomas or other types of cutaneous neoplasms. Although they may be frozen with liquid nitrogen or curetted if they itch or are inflamed, no treatment is needed.
Seborrheic keratosis with “stuck-on appearance” but irregular borders and color variation suspicious for possible melanoma. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Seborrheic keratosis. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
et al. Differentiation of benign pigmented skin lesions with the aid of computer image analysis: a novel approach. Ann Dermatol. 2013 Aug;25(3):340–7.
ESSENTIALS OF DIAGNOSIS
May be flat or raised.
Should be suspected in any pigmented skin lesion with recent change in appearance.
Examination with good light may show varying colors, including red, white, black, and blue.
Borders typically irregular.
Malignant melanoma is the leading cause of death due to skin disease. The reported incidence of melanoma has doubled over the past 30 years. In 2015, approximately 73,870 new melanomas were diagnosed in the United States, with 42,670 cases in men and 31,200 in women. Each year melanoma causes an estimated 9940 deaths (two-thirds in men). One in four cases of melanoma occurs before the age of 40. Increased detection of early melanomas has led to increased survival, but melanoma fatalities continue to increase, especially in men older than 70 years. The lifetime risk of melanoma is 2% in whites, and 0.1–0.5% in nonwhites.
Tumor thickness is the single most important prognostic factor. Ten-year survival rates—related to thickness in millimeters—are as follows: less than 1 mm, 95%; 1–2 mm, 80%; 2–4 mm, 55%; and greater than 4 mm, 30%. With lymph node involvement, the 5-year survival rate is 62%; with distant metastases, it is 16%.
Primary malignant melanomas may be classified into various clinicohistologic types, including lentigo maligna melanoma (arising on chronically sun-exposed skin of older individuals); superficial spreading malignant melanoma (two-thirds of all melanomas arising on intermittently sun-exposed skin); nodular malignant melanoma; acral-lentiginous melanomas (arising on palms, soles, and nail beds); ocular melanoma; and malignant melanomas on mucous membranes. These different clinical types of melanoma appear to have different oncogenic mutations, which may be important in the treatment of patients with advanced disease. Clinical features of pigmented lesions suspicious for melanoma are an irregular notched border where the pigment appears to be spreading into the normal surrounding skin; surface topography that may be irregular, ie, partly raised and partly flat (Figure 6–5) and eFigure 6–8. Color variegation is present and is an important indication for referral. A useful mnemonic is the ABCD rule: “ABCD = Asymmetry, Border irregularity, Color variegation, and Diameter greater than 6 mm.” “E” for Evolution can be added. The history of a changing mole (evolution) is the single most important historical reason for close evaluation and possible referral. Bleeding and ulceration are ominous signs. A mole that appears distinct from the patient’s other moles deserves special scrutiny—the “ugly duckling sign.” A patient with a large number of moles is statistically at increased risk for melanoma and deserves annual total body skin examination by a primary care clinician or dermatologist, particularly if the lesions are atypical. Referral of suspicious pigmented lesions is always appropriate.
Malignant melanoma, with multiple colors and classic “ABCD” features. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Melanoma resembling a seborrheic keratosis on the lateral face of a man. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
While superficial spreading melanoma is largely a disease of whites, persons of other races are still at risk for this and other types of melanoma, particularly acral lentiginous melanomas. These occur as dark, irregularly shaped lesions on the palms and soles and as new, often broad and solitary, darkly pigmented, longitudinal streaks in the nails, typically with involvement of the proximal nail fold (eFigure 6–9). Acral lentiginous melanoma may be a difficult diagnosis because benign pigmented lesions of the hands, feet, and nails occur commonly in more darkly pigmented persons, and clinicians may hesitate to biopsy the palms, soles, and nail beds. As a result, the diagnosis is often delayed until the tumor has become clinically obvious and histologically thick. Clinicians should give special attention to new or changing lesions in these areas.
Superficial spreading malignant melanoma. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Treatment of melanoma consists of excision. After histologic diagnosis, reexcision is recommended with margins dictated by the thickness of the tumor. Thin low-risk and intermediate-risk tumors require margins of 1–3 cm. Surgical margins of 0.5–1 cm for melanoma in situ and 1 cm for lesions less than 1 mm in thickness are recommended.
Sentinel lymph node biopsy (selective lymphadenectomy) using preoperative lymphoscintigraphy and intraoperative lymphatic mapping is effective for staging melanoma patients with intermediate risk without clinical adenopathy and is recommended for all patients with lesions over 1 mm in thickness or with high-risk histologic features (ulceration, high mitotic index). This procedure may not confer a survival advantage. Referral of intermediate-risk and high-risk patients to centers with expertise in melanoma is strongly recommended. Identifying the oncogenic mutations in patients with advanced melanoma may be important because many new treatments targeting oncogenic mutations and immunotherapy now exist.
et al. Sentinel lymph node biopsy in melanoma: controversies and current guidelines. Future Oncol. 2014 Feb;10(3):429–42.
et al. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: Part I: management of stage III disease. J Am Acad Dermatol. 2013 Jan;68(1):1.e1–9.
et al. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: Part II: management of stage IV disease. J Am Acad Dermatol. 2013 Jan;68(1):13.e1–13.
et al. Screening, early detection, education, and trends for melanoma: current status (2007–2013) and future directions: part I. Epidemiology, high-risk groups, clinical strategies, and diagnostic technology. J Am Acad Dermatol. 2014 Oct;71(4):599.e1–599.
et al. Screening, early detection, education, and trends for melanoma: current status (2007–2013) and future directions: part II. Screening, education, and future directions. J Am Acad Dermatol. 2014 Oct;71(4):61.
et al. Interventions for melanoma in situ, including lentigo maligna. Cochrane Database Syst Rev. 2014 Dec 19;12:CD010308.
et al. Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. Br J Dermatol. 2015 Jan;172(1):33–47.
ESSENTIALS OF DIAGNOSIS
Pruritic, xerotic, exudative, or lichenified eruption on face, neck, upper trunk, wrists, and hands and in the antecubital and popliteal folds.
Personal or family history of allergic manifestations (eg, asthma, allergic rhinitis, atopic dermatitis).
Tendency to recur.
Onset in childhood in most patients. Onset after age 30 is very uncommon.
Atopic dermatitis has distinct presentations in people of different ages and races. Diagnostic criteria for atopic dermatitis must include pruritus, typical morphology and distribution (flexural lichenification, hand eczema, nipple eczema, and eyelid eczema in adults), onset in childhood, and chronicity. Also helpful are: (1) a personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis), (2) xerosis-ichthyosis, (3) facial pallor with infraorbital darkening, (4) elevated serum IgE, and (5) repeated skin infections.
Itching is a key clinical feature and may be severe and prolonged. Ill-defined, scaly, red plaques (eFigure 6–10) affect the face, neck, and upper trunk. The flexural surfaces of elbows and knees are often involved. In chronic cases, the skin is dry and lichenified (eFigure 6–11). In dark-skinned patients with severe disease, pigmentation may be lost in lichenified areas (eFigure 6–12). During acute flares, widespread redness with weeping, either diffusely or in discrete plaques, is common.
Atopic dermatitis (eczema). (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Atopic dermatitis of the antecubital folds of a 6-year-old boy. Note the evidence of excoriation and lichenification. (Used, with permission, from S Goldstein.)
The papular appearance is typical of atopic dermatitis in black infants. (Used, with permission, from K Zipperstein.)
Food allergy is an uncommon cause of flares of atopic dermatitis in adults. Eosinophilia and increased serum IgE levels may be present.
Atopic dermatitis must be distinguished from seborrheic dermatitis (less pruritic, frequent scalp and central face involvement, greasy and scaly lesions, and quick response to therapy). Psoriasis is marked by sharply demarcated thickly scaled plaques on elbows, knees, scalp, and intergluteal cleft. Secondary staphylococcal or herpetic infections may exacerbate atopic dermatitis and should be considered during hyperacute, weeping flares of atopic dermatitis (eFigure 6–13). An infra-auricular fissure is a cardinal sign of secondary infection. Since virtually all patients with atopic dermatitis have skin disease before age 5, a new diagnosis of atopic dermatitis in an adult over age 30 should be made only after consultation.
Impetiginization of atopic dermatitis was suspected in this patient when his lesions developed a crusty, weepy character. (Used, with permission, from S Goldstein.)
Patient education regarding gentle skin care and exactly how to use medications is critical to successful management of atopic dermatitis.
Atopic patients have hyperirritable skin. Anything that dries or irritates the skin will potentially trigger dermatitis. Atopic individuals are sensitive to low humidity and often flare in the winter. Adults with atopic disorders should not bathe more than once daily. Soap should be confined to the armpits, groin, scalp, and feet. Washcloths and brushes should not be used. After rinsing, the skin should be patted dry (not rubbed) and then immediately—within minutes—covered with a thin film of an emollient or a corticosteroid as needed. Vanicream can be used if contact dermatitis resulting from additives in medication is suspected. Atopic patients may be irritated by rough fabrics, including wools and acrylics. Cottons are preferable, but synthetic blends also are tolerated. Other triggers of eczema in some patients include sweating, ointments, and heat.
Corticosteroids should be applied sparingly to the dermatitis once or twice daily and rubbed in well. Their potency should be appropriate to the severity of the dermatitis. In general, for treatment of lesions on the body (excluding genitalia, axillary or crural folds), one should begin with triamcinolone 0.1% or a stronger corticosteroid then taper to hydrocortisone or another slightly stronger mild corticosteroid (alclometasone, desonide). It is vital that patients taper off corticosteroids and substitute emollients as the dermatitis clears to avoid side effects of corticosteroids. Tapering is also important to avoid rebound flares of the dermatitis that may follow their abrupt cessation. Tacrolimus ointment (Protopic 0.03% or 0.1%) and pimecrolimus cream (Elidel 1%) can be effective in managing atopic dermatitis when applied twice daily. Burning on application occurs in about 50% of patients using Protopic and in 10–25% of Elidel users, but it may resolve with continued treatment. These medications do not cause skin atrophy or striae, avoiding the complications of long-term topical corticosteroid use. They are safe for application on the face and even the eyelids but are more expensive than generic topical corticosteroids.
The US Food and Drug Administration (FDA) has issued a black box warning for both topical tacrolimus and pimecrolimus due to concerns about the development of T-cell lymphoma. The agents should be used sparingly and only in locations where less expensive corticosteroids cannot be used. They should be avoided in patients at high risk for lymphoma (ie, those with HIV, iatrogenic immunosuppression, or prior lymphoma).
The treatment of atopic dermatitis is dictated by the pattern and stage of the dermatitis—acute/weepy, subacute/scaly, or chronic/lichenified.
(eFigure 6–14) Staphylococcal or herpetic superinfection should be formally excluded. Use water or aluminum subacetate solution (Domeboro tablets, one in a pint of cool water), or colloidal oatmeal (Aveeno; dispense one box, and use as directed on box) as soothing or astringent soaks, baths, or wet dressings for 10–30 minutes two to four times daily. Lesions on extremities particularly may be bandaged for protection at night. Use high-potency corticosteroids after soaking, but spare the face and body folds. Tacrolimus is usually not tolerated at this stage. Systemic corticosteroids may be required.
Vesicular eczema. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
2. Subacute or scaly lesions
(eFigure 6–15) At this stage, the lesions are dry but still red and pruritic. Mid- to high-potency corticosteroids in ointment form should be continued until scaling and elevated skin lesions are cleared and itching is decreased substantially. At that point, patients should begin a 2- to 4-week taper from twice-daily to daily dosing with topical corticosteroids to reliance on emollients, with occasional use of corticosteroids only to inflamed areas. It is preferable to switch to daily use of a low-potency corticosteroid instead of further tapering the frequency of usage of a more potent corticosteroid. Tacrolimus and pimecrolimus may be substituted if corticosteroids cannot be stopped completely.
Patchy atopic dermatitis on the thighs. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
3. Chronic, dry, lichenified lesions
Thickened and usually well demarcated, they are best treated with high-potency to ultra–high-potency corticosteroid ointments. Nightly occlusion for 2–6 weeks may enhance the initial response. Adding tar preparations, such as liquor carbonis detergens (LCD) 10% in Aquaphor or 2% crude coal tar may be beneficial.
Once symptoms have improved, constant application of effective moisturizers is recommended to prevent flares. In patients with moderate disease, use of topical anti-inflammatories only on weekends or three times weekly can prevent flares.
C. Systemic and Adjuvant Therapy
Systemic corticosteroids are indicated only for severe acute exacerbations. Oral prednisone dosages should be high enough to suppress the dermatitis quickly, usually starting with 1 mg/kg daily for adults. The dosage is then tapered off over a period of 2–4 weeks. Owing to the chronic nature of atopic dermatitis and the side effects of long-term systemic corticosteroids, ongoing use of these agents is not recommended for maintenance therapy. Bedtime doses of hydroxyzine, diphenhydramine, or doxepin may be helpful via their sedative properties to mitigate perceived pruritus. Fissures, crusts, erosions, or pustules indicate staphylococcal or herpetic infection clinically. Systemic antistaphylococcal antibiotics—such as a first-generation cephalosporin or doxycycline if methicillin-resistant Staphylococcus aureus is suspected—should be given only if indicated and guided by bacterial culture. Cultures to exclude methicillin-resistant S aureus are recommended. In this setting, continuing and augmenting the topical anti-inflammatory treatment often improves the dermatitis despite the presence of infection. Phototherapy can be an important adjunct for severely affected patients, and the properly selected patient with recalcitrant disease may benefit greatly from therapy with UVB with or without coal tar or (psoralen plus ultraviolet A [PUVA]). Oral cyclosporine, mycophenolate mofetil, methotrexate, interferon gamma, dupilumab (undergoing phase III trials), tofacitinib, or azathioprine may be used for the most severe and recalcitrant cases.
Complications of Treatment
The clinician should monitor for skin atrophy. Eczema herpeticum, a generalized herpes simplex infection manifested by monomorphic vesicles, crusts, or scalloped erosions superimposed on atopic dermatitis or other extensive eczematous processes, is treated successfully with oral acyclovir, 200 mg five times daily, or intravenous acyclovir in a dose of 10 mg/kg intravenously every 8 hours (500 mg/m2 every 8 hours) (eFigure 6–16). Smallpox vaccination is absolutely contraindicated in patients with atopic dermatitis or a history thereof because of the risk of eczema vaccinatum (widespread vaccinia infection, preferentially in areas of dermatitis).
A patch of eczema herpeticum composed of umbilicated vesicles with central large erosion. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Atopic dermatitis runs a chronic or intermittent course. Affected adults may have only hand dermatitis. Poor prognostic factors for persistence into adulthood in atopic dermatitis include generalized disease or onset early in childhood and asthma. Only 40–60% of these patients have lasting remissions.
et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338–51.
et al. Guidelines of care for the management of atopic dermatitis: section 2. Guidelines of care for the management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014 Jul;71(1):116–32.
et al. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015 Sep;73(3):395–9.
et al. The association between atopic dermatitis and food allergy in adults. Curr Opin Allergy Clin Immunol. 2014 Oct;14(5):423–9.
et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014 Aug;71(2):327–49.
et al. Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. 2014 Dec;71(6):1218–33.
et al. Efficacy and safety of dupulimumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomized, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2015 Oct 7. [Epub ahead of print]
LICHEN SIMPLEX CHRONICUS (Circumscribed Neurodermatitis)
ESSENTIALS OF DIAGNOSIS
Chronic itching and scratching.
Lichenified lesions with exaggerated skin lines overlying a thickened, well-circumscribed, scaly plaque.
Predilection for nape of neck, wrists, external surfaces of forearms, lower legs, scrotum, and vulva.
Lichen simplex chronicus represents a self-perpetuating scratch-itch cycle that is hard to disrupt.
Intermittent itching incites the patient to scratch the lesions. Itching may be so intense as to interfere with sleep. Dry, hypertrophic, lichenified plaques appear on the neck, ankles, or perineum (eFigure 6–17) (eFigure 6–18). The patches are rectangular, thickened, and hyperpigmented. The skin lines are exaggerated.
Lichen simplex chronicus. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Lichen simplex chronicus resulting from repeated itch-scratch cycles. Note the hypertrophic leathery, lichenified plaques. The exaggerated skin lines are characteristic. (Used, with permission, from S Goldstein.)
This disorder can be differentiated from plaque-like lesions such as psoriasis (redder lesions having whiter scales on the elbows, knees, and scalp and nail findings) (eFigure 6–22), lichen planus (violaceous, usually smaller polygonal papules), and nummular (coin-shaped) dermatitis (eFigure 6–19). Lichen simplex chronicus may complicate chronic atopic dermatitis or scabetic infestation.
Nummular dermatitis presents as more acute round, scaly, or moist lesions without marked lichenification. (Used, with permission, from S Goldstein.)
For lesions in extra-genital regions, superpotent topical corticosteroids are effective, with or without occlusion, when used twice daily for several weeks. In some patients, flurandrenolide (Cordran) tape may be effective, since it prevents scratching and rubbing of the lesion. The injection of triamcinolone acetonide suspension (5–10 mg/mL) into the lesions may occasionally be curative. Continuous occlusion with a flexible hydrocolloid dressing for 7 days at a time for 1–2 months may also be helpful. For genital lesions, see the section Pruritus Ani.
The disease tends to remit during treatment but may recur or develop at another site.
et al. Quality of life of patients with neurodermatitis. Int J Med Sci. 2013;10(5):593–8.
et al. Efficacy of treatment with oral alitretinoin in patient suffering from lichen simplex chronicus and severe atopic dermatitis of hands. Dermatol Ther. 2014 Jan–Feb;27(1):21–3.
et al. Increased risk of lichen simplex chronicus in people with anxiety disorder: a nationwide population-based retrospective cohort study. Br J Dermatol. 2014 Apr;170(4):890–4.
ESSENTIALS OF DIAGNOSIS
Silvery scales on bright red, well-demarcated plaques, usually on the knees, elbows, and scalp.
Nail findings including pitting and onycholysis (separation of the nail plate from the bed).
Mild itching (usually).
May be associated with psoriatic arthritis.
Psoriasis patients are at increased risk for cardiovascular events, type 2 diabetes mellitus, metabolic syndrome, and lymphoma.
Histopathology can be helpful to exclude clinical mimics.
Psoriasis is a common benign, chronic inflammatory skin disease with both a genetic basis and known environmental triggers. Injury or irritation of normal skin tends to induce lesions of psoriasis at the site (Koebner phenomenon) (eFigure 6–20) (eFigure 6–21). Obesity worsens psoriasis, and significant weight loss in obese persons may lead to substantial improvement of their psoriasis. Psoriasis has several variants—the most common is the plaque type (eFigure 6–22) (eFigure 6–23) (eFigure 6–24). Eruptive (guttate) psoriasis consisting of myriad lesions 3–10 mm in diameter occurs occasionally after streptococcal pharyngitis. Rarely, grave, occasionally life-threatening forms (generalized pustular and erythrodermic psoriasis) may occur.
Koebner phenomenon on skin of the hands.
Koebner phenomenon on the extremities.
Psoriasis. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Generalized plaque-type psoriasis with symmetric distribution. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]: Dermatology. Originally published by Appleton & Lange. Copyright 1991 by The McGraw-Hill Companies, Inc.)
A, B: Plaque-like psoriasis of the scalp with characteristic silvery, thick scale distinguishes it from seborrheic dermatitis of the scalp. (Used, with permission, from S Goldstein.)
There are often no symptoms, but itching may occur and be severe. Favored sites include the scalp, elbows, knees, palms and soles, and nails. The lesions are red, sharply defined plaques covered with silvery scales (Figure 6–6). The glans penis and vulva may be affected. Occasionally, only the flexures (axillae, inguinal areas) are involved (termed inverse psoriasis). Fine stippling (“pitting”) in the nails is highly suggestive of psoriasis (Figure 6–7) (eFigure 6–25). Patients with psoriasis often have a pink or red intergluteal fold (Figure 6–6). Not all patients have findings in all locations, but the occurrence of a few may help make the diagnosis when other lesions are not typical. Some patients have mainly hand or foot dermatitis and only minimal findings elsewhere. There may be associated arthritis that is most commonly distal and oligoarticular, although the rheumatoid variety with a negative rheumatoid factor may occur (eFigure 6–26). The psychosocial impact of psoriasis is a major factor in determining the treatment of the patient.
Plaque psoriasis in the sacral region and intergluteal fold. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Nail pitting due to psoriasis. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Nails from a patient with psoriasis demonstrating pitting and onycholysis. (Used, with permission, from S Goldstein.)
Psoriasis of nails and nail beds, with associated arthritis at the terminal interphalangeal joint. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
The combination of red plaques with silvery scales on elbows and knees, with scaliness in the scalp or nail findings, is diagnostic. Psoriasis lesions are well demarcated and affect extensor surfaces—in contrast to atopic dermatitis, with poorly demarcated plaques in flexural distribution (eFigure 6–10). In body folds, scraping and culture for Candida and examination of scalp and nails will distinguish “inverse psoriasis” from intertrigo and candidiasis (eFigure 6–27). Dystrophic changes in nails may mimic onychomycosis, and a potassium hydroxide (KOH) preparation or fungal culture is valuable in diagnosis (eFigure 6–28). The cutaneous features of reactive arthritis, pityriasis rosea, systemic lupus erythematosus, and syphilis mimic psoriasis.
Intertrigo involving the axillary fold of an infant. (Used, with permission, from K Zipperstein.)
Onychomycosis involving digits 1, 2, and 5. (Used, with permission, from K Zipperstein.)
There are many therapeutic options in psoriasis to be chosen according to the extent (body surface area [BSA] affected) and the presence of other findings (for example, arthritis). Certain medications, such as beta-blockers, antimalarials, statins, and lithium, may flare or worsen psoriasis. Even tiny doses of systemic corticosteroids given to patients with psoriasis may lead to severe rebound flares of their disease when they are tapered. Systemic corticosteroids should never be used to treat flares of psoriasis. Patients with moderate to severe psoriasis should be managed by or in conjunction with a dermatologist.
High- to ultra–high-potency topical corticosteroids are the mainstay for limited disease (less than 10% BSA). For patients with numerous small plaques, phototherapy is the best therapy. For patients with large plaques and less than 10% of the BSA involved, the easiest regimen is to use a high-potency to ultra–high-potency topical corticosteroid cream or ointment. It is best to restrict the ultra–high-potency corticosteroids to 2–3 weeks of twice-daily use and then use them in a pulse fashion three or four times on weekends or switch to a mid-potency corticosteroid. Topical corticosteroids rarely induce a lasting remission. Additional measures are therefore commonly added to topical corticosteroid therapy. Calcipotriene ointment 0.005% or calcitriol ointment 0.003%, both vitamin D analogs, are used twice daily for plaque psoriasis. Initially, patients are treated with twice-daily corticosteroids plus a vitamin D analog twice daily. This rapidly clears the lesions. The vitamin D analog is then used alone once daily and with the corticosteroid once daily for several weeks. Eventually, the topical corticosteroids are stopped, and once- or twice-daily application of the vitamin D analog is continued long-term. Calcipotriene usually cannot be applied to the groin or face because of irritation. Treatment of extensive psoriasis with vitamin D analogs may result in hypercalcemia, so that the maximum dose for calcipotriene is 100 g/week and for calcitriol is 200 g/week. Calcipotriene is incompatible with many topical corticosteroids (but not halobetasol), so if used concurrently, it must be applied at a different time. Tar preparations, such as Fototar cream and LCD 10% in Nutraderm lotion, alone or mixed directly with triamcinolone 0.1%, are useful adjuncts when applied twice daily. Occlusion alone has been shown to clear isolated plaques in 30–40% of patients. Thin, occlusive hydrocolloid dressings are placed on the lesions and left undisturbed for as long as possible (a minimum of 5 days, up to 7 days) and then replaced. Responses may be seen within several weeks.
For the scalp, start with a tar shampoo, used daily if possible. For thick scales, use 6% salicylic acid gel (eg, Keralyt), P & S solution (phenol, mineral oil, and glycerin), or fluocinolone acetonide 0.01% in oil (Derma-Smoothe/FS) under a shower cap at night, and shampoo in the morning. In order of increasing potency, triamcinolone 0.1%, fluocinolone, betamethasone dipropionate, amcinonide, and clobetasol are available in solution form for use on the scalp twice daily. For psoriasis in the body folds, treatment is difficult, since potent corticosteroids cannot be used and other agents are poorly tolerated. Tacrolimus ointment 0.1% or 0.03% or pimecrolimus cream 1% may be effective in intertriginous, genital, and facial psoriasis.
Psoriasis affecting 10–30% of the patient’s BSA is frequently treated with UV phototherapy, either in a medical office or via a home light unit. Systemic agents listed below may also be used.
If psoriasis involves more than 30% of the body surface, it is difficult to treat with topical agents. The treatment of choice is outpatient narrowband UVB (NB-UVB) three times weekly. Clearing occurs in an average of 7 weeks, and maintenance may be required. Severe psoriasis unresponsive to outpatient ultraviolet light may be treated in a psoriasis day care center with the Goeckerman regimen, which involves use of crude coal tar for many hours and exposure to UVB light. Such treatment may offer the best chance for prolonged remissions.
Psoralen plus UVA (PUVA) photochemotherapy may be effective even in patients who have not responded to standard NB-UVB treatment. Long-term use of PUVA (greater than 250 doses) is associated with an increased risk of skin cancer (especially squamous cell carcinoma and perhaps melanoma) in persons with fair complexions. Thus, periodic examination (every 3–6 months) of the skin is imperative. Atypical lentigines are a common complication. There can be rapid aging of the skin in fair individuals. Cataracts have not been reported with proper use of protective glasses. PUVA may be used in combination with other therapy, such as acitretin or methotrexate.
Methotrexate is very effective for severe psoriasis in doses up to 25 mg once weekly. It should be used according to published protocols. Long-term methotrexate use may be associated with cirrhosis. After receiving a 3.5–4-g cumulative dose, the patient should be referred to a hepatologist for consideration of a liver biopsy. Administration of folic acid, 1–2 mg daily, can eliminate nausea caused by methotrexate without compromising efficacy.
Acitretin, a synthetic retinoid, is most effective for pustular psoriasis in dosages of 0.5–0.75 mg/kg/day. Liver enzymes and serum lipids must be checked periodically. Because acitretin is a teratogen and persists for 2–3 years in fat, women of childbearing age must wait at least 3 years after completing acitretin treatment before considering pregnancy. When used as single agents, retinoids will flatten psoriatic plaques, but will rarely result in complete clearing. Retinoids find their greatest use when combined with phototherapy—either UVB or PUVA, with which they are synergistic.
Cyclosporine dramatically improves psoriasis and may be used to control severe cases. Rapid relapse (rebound) is the rule after cessation of therapy, so another agent must be added if cyclosporine is stopped. The tumor necrosis factor (TNF) inhibitors etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) are effective in pustular and chronic plaque psoriasis and are also effective for the associated arthritis. Infliximab provides the most rapid response and can be used for severe pustular or erythrodermic flares. Etanercept is used more frequently for long-term treatment at a dose of 50 mg twice weekly for 3 months, then 50 mg once weekly. All three TNF inhibitors can also induce or worsen psoriasis. IL-12/23 monoclonal antibodies (ustekinumab [Stelara], guselkumab), Janus kinase inhibitors (tofacitinib, undergoing phase III clinical trials), and IL-17 monoclonal antibodies (secukinumab, as well as the medications in clinical trials brodalumab and ixekizumab) are showing promise as alternative treatments. The phosphodiesterase 4 inhibitor apremilast is an approved option for plaque-type psoriasis with minimal immunosuppressive effects. Given the large number of psoriasis treatments available, consultation with a dermatologist is recommended when considering systemic treatment for moderate to severe psoriasis.
The course tends to be chronic and unpredictable, and the disease may be refractory to treatment. Patients (especially those older than 40 years) should be monitored for metabolic syndrome, which correlates with the severity of their skin disease.
et al. Combining biologic therapies with other systemic treatments in psoriasis: evidence-based, best-practice recommendations from the Medical Board of the National Psoriasis Foundation. JAMA Dermatol. 2015 Apr;151(4):432–8.
et al. Treating moderate to severe psoriasis—best use of biologics. Expert Rev Clin Immunol. 2014 Feb;10(2):269–79.
et al. Topical treatments for chronic plaque psoriasis: an abridged Cochrane Systematic Review. J Am Acad Dermatol. 2013 Nov;69(5):799–807.
et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015 Jul;73(1):37–49.
et al. Evidence-based recommendations on the role of dermatologists in the diagnosis and management of psoriatic arthritis: systematic review and expert opinion. J Eur Acad Dermatol Venereol. 2014 Aug;28(Suppl 5):3–12.
et al. Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response. Br J Dermatol. 2015 Feb;173(2):504–12.
ESSENTIALS OF DIAGNOSIS
Oval, fawn-colored, scaly eruption following cleavage lines of trunk.
Herald patch precedes eruption by 1–2 weeks.
This is a common mild, acute inflammatory disease that is 50% more common in females. Young adults are principally affected, mostly in the spring or fall. Concurrent household cases have been reported.
Itching is common but is usually mild. The diagnosis is made by finding one or more classic lesions. The lesions consist of oval, fawn-colored plaques up to 2 cm in diameter (eFigure 6–29) (eFigure 6–30). The centers of the lesions have a crinkled or “cigarette paper” appearance and a collarette scale, ie, a thin bit of scale that is bound at the periphery and free in the center. Only a few lesions in the eruption may have this characteristic appearance, however. Lesions follow cleavage lines on the trunk (so-called Christmas tree pattern, Figure 6–8), and the proximal portions of the extremities are often involved. A variant that affects the flexures (axillae and groin), so-called “inverse pityriasis rosea,” and a papular variant, especially in black patients, also occur. An initial lesion (“herald patch”) that is often larger than the later lesions often precedes the general eruption by 1–2 weeks. The eruption usually lasts 6–8 weeks and heals without scarring.
Pityriasis rosea with scaling lesions following skin lines and resembling a Christmas tree. (From EJ Mayeaux, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Pityriasis rosea. (Used, with permission, from Berger TG, Dept. Dermatology, UCSF.)
Pityriasis rosea. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
A serologic test for syphilis, such as a rapid plasma reagin (RPR) test, should be performed if at least a few perfectly typical lesions are not present and especially if there are palmar and plantar or mucous membrane lesions or adenopathy, features that are suggestive of secondary syphilis (eFigure 6–31) (eFigure 6–32) (eFigure 6–33). Tinea corporis may present with red, slightly scaly plaques, but rarely are there more than a few lesions of tinea corporis compared to the many lesions of pityriasis rosea (eFigure 6–34). A potassium hydroxide examination should be performed to exclude a fungal cause. Seborrheic dermatitis on occasion presents on the body with poorly demarcated patches over the sternum, in the pubic area, and in the axillae (eFigure 6–35). Tinea versicolor lacks the typical collarette rimmed lesions (eFigure 6–36). Certain medications (eg, angiotensin-converting enzyme [ACE] inhibitors and metronidazole) and immunizations rarely may induce a skin eruption mimicking pityriasis rosea.
Classic lesions of secondary syphilis include red-brown, copper, or ham-colored macules or papulosquamous lesions on the palms. (Used, with permission, from S Goldstein.)
Classic lesions of secondary syphilis include red-brown, copper, or ham-colored macules or papulosquamous lesions on the soles of the feet. (Used, with permission, from S Goldstein.)
Maculopapular skin eruption of secondary syphilis. (Used, with permission, from S Goldstein.)
Tinea corporis. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Seborrheic dermatitis of the chest/ presternal area. (Used, with permission, from S Goldstein.)
Pityriasis (tinea) versicolor: Multiple, small- to medium-sized, well-demarcated hypopigmented macules on the back of a tanned individual with white skin. (Reproduced, with permission, from Wolff K et al (editors). Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology, 7e. McGraw-Hill, 2012.)
Pityriasis rosea often requires no treatment. In darker-skinned individuals, in whom lesions may remain hyperpigmented for some time, more aggressive management may be indicated. Treatment is, otherwise, indicated only if the patient is symptomatic. While adequately controlled and reproduced trials have not demonstrated widely effective treatments, most dermatologists recommend UVB treatments or a short course of prednisone for severe or severely symptomatic cases. For mild to moderate cases, topical corticosteroids of medium strength (triamcinolone 0.1%) and oral antihistamines may also be used if pruritus is bothersome. The role of macrolide antibiotics is controversial.
Pityriasis rosea is usually an acute self-limiting illness that typically disappears in about 6 weeks although prolonged variants have been reported.
et al. Persistent pityriasis rosea: an unusual form of pityriasis rosea with persistent active HHV-6 and HHV-7 infection. Dermatology. 2015;230(1):23–6.
et al. Coexistence of two atypical variants of pityriasis rosea: a case report and review of literature. Pediatr Dermatol. 2012 Jul–Aug;29(4):538–40.
ESSENTIALS OF DIAGNOSIS
Dry scales and underlying erythema.
Scalp, central face, presternal, interscapular areas, umbilicus, and body folds.
Seborrheic dermatitis is an acute or chronic papulosquamous dermatitis that often coexists with psoriasis.
The scalp, face, chest, back, umbilicus, eyelid margins, genitalia, and body folds have dry scales (dandruff) or oily yellowish scurf (Figure 6–9) (eFigure 6–37) (eFigure 6–38) (eFigure 6–39). Pruritus is a variable finding. Patients with Parkinson disease, HIV infection, and patients who become acutely ill often have seborrheic dermatitis.
Seborrheic dermatitis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Seborrheic dermatitis of the scalp. (Used, with permission, from S Goldstein.)
Seborrheic dermatitis. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Extensive seborrheic dermatitis on the face, trunk, and limbs of a young infant. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
There is a spectrum from seborrheic dermatitis to scalp psoriasis (eFigure 6–37) (eFigure 6–24). Extensive seborrheic dermatitis may simulate intertrigo in flexural areas, but scalp, face, and sternal involvement suggests seborrheic dermatitis.
A. Seborrhea of the Scalp
Shampoos that contain zinc pyrithione or selenium are used daily if possible. These may be alternated with ketoconazole shampoo (1% or 2%) used twice weekly. A combination of shampoos is used in refractory cases. Tar shampoos are also effective for milder cases and for scalp psoriasis. Topical corticosteroid solutions or lotions are then added if necessary and are used twice daily. (See treatment for scalp psoriasis, above.)
B. Facial Seborrheic Dermatitis
The mainstay of therapy is a mild corticosteroid (hydrocortisone 1%, alclometasone, desonide) used intermittently and not near the eyes. If the disorder cannot be controlled with intermittent use of a mild topical corticosteroid alone, ketoconazole (Nizoral) 2% cream is added twice daily. Topical tacrolimus (Protopic) and pimecrolimus (Elidel) are steroid-sparing alternatives.
C. Seborrheic Dermatitis of Nonhairy Areas
Low-potency corticosteroid creams—ie, 1% or 2.5% hydrocortisone, desonide, or alclometasone dipropionate—are highly effective.
D. Seborrhea of Intertriginous Areas
Apply low-potency corticosteroid lotions or creams twice daily for 5–7 days and then once or twice weekly for maintenance as necessary. Selenium lotion, ketoconazole, or clotrimazole gel or cream may be a useful adjunct. Tacrolimus or pimecrolimus topically may avoid corticosteroid atrophy in chronic cases.
E. Involvement of Eyelid Margins
“Marginal blepharitis” usually responds to gentle cleaning of the lid margins nightly as needed, with undiluted Johnson & Johnson Baby Shampoo using a cotton swab.
The tendency is for lifelong recurrences. Individual outbreaks may last weeks, months, or years.
et al. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies. Clin Dermatol. 2013 Jul–Aug;31(4):343–51.
et al. Systematic review of oral treatments for seborrheic dermatitis. J Eur Acad Dermatol Venereol. 2014 Jan;28(1):16–26.
FUNGAL INFECTIONS OF THE SKIN
Mycotic infections are traditionally divided into two principal groups—superficial and deep. In this chapter, only the superficial infections are discussed: tinea corporis and tinea cruris; dermatophytosis of the feet and dermatophytid of the hands; tinea unguium (onychomycosis); and tinea versicolor. See Chapter 36 for discussion of deep mycoses.
The diagnosis of fungal infections of the skin is usually based on the location and characteristics of the lesions and on the following laboratory examinations: (1) Direct demonstration of fungi in 10% KOH evaluation of suspected lesions. “If it’s scaly, scrape it” is a time-honored maxim (Figure 6–10) (eFigure 6–40). (2) Cultures of organisms from skin scrapings. (3) Histologic sections of biopsies stained with periodic acid-Schiff technique may be diagnostic if scrapings and cultures are falsely negative.
KOH preparation of fungus demonstrating pseudohyphae and budding yeast forms. (Reproduced, with permission, from Nicoll D et al. Pocket Guide to Diagnostic Tests, 6th ed. McGraw-Hill, 2012.)
Branched hyphae of fungal infection demonstrated by potassium hydroxide (KOH) examination. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
A diagnosis should always be confirmed by KOH preparation, culture, or biopsy. Many other diseases cause scaling, and use of an antifungal agent without a firm diagnosis makes subsequent diagnosis more difficult. In general, fungal infections are treated topically except for those with extensive involvement or involving the nails or hair follicles. In these situations, oral agents may be useful, with special attention to their side effects and complications, including hepatic toxicity.
Itraconazole, an azole antifungal, and terbinafine, an allylamine oral antifungal, have excellent activity against dermatophytes. Fluconazole has excellent activity against yeasts and is the treatment of choice for most forms of mucocutaneous candidiasis. Itraconazole, fluconazole, and terbinafine can all cause elevation of liver function tests and—though rarely in the dosing regimens used for the treatment of dermatophytosis—clinical hepatitis. Ketoconazole is no longer recommended for the treatment of dermatophytosis (except for tinea versicolor) because of the higher rate of hepatitis.
General Measures & Prevention
Since moist skin favors the growth of fungi, dry the skin carefully after bathing or after perspiring heavily. Talc or other drying powders may be useful with the exception of powders containing corn starch, which may exacerbate fungal infections. The use of topical corticosteroids for other diseases may be complicated by intercurrent tinea or candidal infection, and topical antifungals are often used in intertriginous areas with corticosteroids to prevent this.
1. Tinea Corporis or Tinea Circinata
The lesions are often on exposed areas of the body such as the face and arms. A history of exposure to an infected pet may occasionally be obtained, usually indicating Microsporum infection. Trichophyton rubrum is the most common pathogen, usually representing extension onto the trunk or extremities of tinea cruris, pedis, or manuum.
Itching may be present. In classic lesions, rings of erythema have an advancing scaly border and central clearing (Figure 6–11) (eFigure 6–34) (eFigure 6–41) (eFigure 6–42).
Tinea pedis and corporis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Tinea corporis. (Used, with permission, from Berger TG, Dept. Dermatology, UCSF.)
Tinea corporis: scaly, ring-shaped lesions with distinct borders and central clearing. (Used, with permission, from S Goldstein.)
The diagnosis should be confirmed by KOH preparation or culture.
Positive fungal studies distinguish tinea corporis from other skin lesions with annular configuration, such as the annular lesions of psoriasis (eFigure 6–43), lupus erythematosus, syphilis, granuloma annulare, and pityriasis rosea. Psoriasis has typical lesions on elbows, knees, scalp, and nails. Secondary syphilis is often manifested by characteristic palmar, plantar, and mucous membrane lesions. Tinea corporis rarely has the large number of symmetric lesions seen in pityriasis rosea (eFigure 6–30). Granuloma annulare lacks scale.
Annular psoriasis can mimic tinea corporis. (Used, with permission, from I Frieden.)
Complications include extension of the disease down the hair follicles (which presents as papules and pustules and is more difficult to cure) and pyoderma.
Treat infected household pets (Microsporum infections). To prevent recurrences, the use of foot powder and keeping feet dry by wearing sandals, or changing socks can be useful.
Tinea corporis responds to most topical antifungals, including econazole, miconazole, clotrimazole, butenafine, and terbinafine, most of which are available over the counter in the United States (see Table 6–2). Terbinafine and butenafine require shorter courses and lead to the most rapid response. Treatment should be continued for 1–2 weeks after clinical clearing. Betamethasone dipropionate with clotrimazole (Lotrisone) is not recommended. Long-term improper use may result in side effects from the high-potency corticosteroid component, especially in body folds.
Itraconazole as a single week-long pulse of 200 mg daily is also effective in tinea corporis. Terbinafine, 250 mg daily for 1 month, is an alternative.
Tinea corporis usually responds promptly to conservative topical therapy or to an oral agent within 4 weeks.
et al. Topical antifungal treatments for tinea cruris and tinea corporis. Cochrane Database Syst Rev. 2014 Aug 4;8:CD009992.
2. Tinea Cruris (Jock Itch)
ESSENTIALS OF DIAGNOSIS
Marked itching in intertriginous areas, usually sparing the scrotum.
Peripherally spreading, sharply demarcated, centrally clearing erythematous lesions.
May have associated tinea infection of feet or toenails.
Laboratory examination with microscope or culture confirms diagnosis.
Tinea cruris lesions are confined to the groin and gluteal cleft. Intractable pruritus ani may occasionally be caused by a tinea infection.
Itching may be severe, or the rash may be asymptomatic. The lesions have sharp margins, cleared centers, and active, spreading scaly peripheries (eFigure 6–44). Follicular pustules are sometimes encountered. The area may be hyperpigmented on resolution.
Tinea cruris. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Hyphae can be demonstrated microscopically in KOH preparations or skin biopsy. The organism may be cultured.
Tinea cruris must be distinguished from other lesions involving the intertriginous areas, such as candidiasis, seborrheic dermatitis, intertrigo, psoriasis of body folds (“inverse psoriasis”), and erythrasma. Candidiasis is generally bright red and marked by satellite papules and pustules outside of the main border of the lesion (eFigure 6–45). Candida typically involves the scrotum. Seborrheic dermatitis also often involves the face, sternum, and axillae. Intertrigo tends to be more red, less scaly, and present in obese individuals in moist body folds with less extension onto the thigh. “Inverse psoriasis” is characterized by distinct plaques (eFigure 6–46). Other areas of typical psoriatic involvement should be checked, and the KOH examination will be negative. Erythrasma is best diagnosed with Wood (ultraviolet) light—a brilliant coral-red fluorescence is seen (eFigure 6–47) (eFigure 6–48).
Extensive candidiasis originating in the groin in an infant. (Used, with permission, from S Goldstein.)
Inverse psoriasis in the groin is distinguished from Candida infections by history and KOH staining. Unlike tinea cruris, the scrotum is affected. (Used, with permission, from K Zipperstein.)
Erythrasma presenting in the axillary fold. (Used, with permission, from K Zipperstein.)
A diagnostic feature of erythrasma is the coral-red fluorescence observed here in focal distribution under a Wood light. (Used, with permission, from K Zipperstein.)
Drying powder (eg, miconazole nitrate [Zeasorb-AF]) can be dusted into the involved area in patients with excessive perspiration or occlusion of skin due to obesity.
Any of the topical antifungal preparations listed in Table 6–2 may be used. Terbinafine cream is curative in over 80% of cases after once-daily use for 7 days.
One week of either itraconazole, 200 mg daily, or terbinafine, 250 mg daily, can be effective. Griseofulvin ultramicrosize 250–500 mg orally twice daily for 1–2 weeks is reserved for severe cases.
Tinea cruris usually responds promptly to topical or systemic treatment but often recurs.
et al. Intertrigo and secondary skin infections. Am Fam Physician. 2014 Apr;89(7):569–73.
3. Tinea Manuum & Tinea Pedis (Dermatophytosis, Tinea of Palms & Soles, “Athlete’s Foot”)
ESSENTIALS OF DIAGNOSIS
Most often presents with asymptomatic scaling.
May progress to fissuring or maceration in toe web spaces.
May be a portal of entry for bacteria causing lower extremity cellulitis.
Itching, burning, and stinging of interdigital web; scaling palms and soles; vesicles of soles in inflammatory cases.
The fungus is shown in skin scrapings examined microscopically or by culture of scrapings.
Tinea of the feet is an extremely common acute or chronic dermatosis. Most infections are caused by Trichophyton species.
The presenting symptom may be itching, burning, or stinging. Pain may indicate secondary infection with complicating cellulitis. Interdigital tinea pedis is the most common predisposing cause of lower extremity cellulitis in healthy individuals. Regular examination of the feet of diabetic patients for evidence of scaling and fissuring and treatment of any identified tinea pedis may prevent complications. Tinea pedis has several presentations that vary with the location (eFigure 6–49). On the sole and heel, tinea may appear as chronic noninflammatory scaling, occasionally with thickening and fissuring. This may extend over the sides of the feet in a “moccasin” distribution. The KOH preparation is usually positive. Tinea pedis often appears as a scaling or fissuring of the toe webs, often with maceration (Figure 6–12). As the web spaces become more macerated, the KOH preparation and fungal culture are less often positive because bacterial species begin to dominate. Finally, there may also be vesicles, bullae, or generalized exfoliation of the skin of the soles, or nail involvement in the form of discoloration, friability, and thickening of the nail plate.
Tinea pedis in the interdigital space between fourth and fifth digits. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
A: Interdigital tinea pedis: Maceration is prominent. B: Vesicular tinea pedis: Grouped vesicles on the lateral aspect of the foot at the plantar-glabrous skin junction. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
KOH and culture do not always demonstrate pathogenic fungi from macerated areas.
Differentiate from other skin conditions involving the same areas, such as interdigital erythrasma (use Wood light). Psoriasis may be a cause of chronic scaling on the palms or soles and may cause nail changes. Repeated fungal cultures should be negative, and the condition will not respond to antifungal therapy. Contact dermatitis will often involve the dorsal surfaces and will respond to topical or systemic corticosteroids (eFigure 6–50). Vesicular lesions should be differentiated from pompholyx (dyshidrosis) (eFigure 6–51) and scabies (eFigure 6–52) by proper scraping of the roofs of individual vesicles. Rarely, gram-negative organisms may cause toe web infections, manifested as an acute erosive flare of interdigital disease. This entity is treated with aluminum salts and imidazole antifungal agents or ciclopirox. Candida may also cause erosive interdigital disease.
Allergic contact dermatitis due to nickel. A chronic nature is suggested by the scaling and thickened skin. (Used, with permission, from R Odom.)
Pompholyx: classic "tapioca" vesicles may be intensely pruritic leading to scaling and fissuring in advanced cases. (Used, with permission, from S Goldstein.)
Typical site for excoriated, vesiculopustular lesions due to scabies. (Used, with permission, from S Goldstein.)
The essential factor in prevention is personal hygiene. Wear open-toed sandals if possible. Use of sandals in community showers and bathing places is often recommended, though the effectiveness of this practice has not been studied. Careful drying between the toes after showering is essential. A hair dryer used on low setting may be used. Socks should be changed frequently, and absorbent nonsynthetic socks are preferred. Apply dusting and drying powders as necessary. The use of powders containing antifungal agents (eg, Zeasorb-AF) or long-term use of antifungal creams may prevent recurrences of tinea pedis.
Treat with aluminum subacetate solution soaks for 20 minutes twice daily. Broad-spectrum antifungal creams and solutions (containing imidazoles or ciclopirox) will help combat diphtheroids and other gram-positive organisms present at this stage and alone may be adequate therapy. If topical imidazoles fail, 1 week of once-daily topical allylamine treatment (terbinafine or butenafine) will often result in clearing.
Use any of the antifungal agents listed in Table 6–2. The addition of urea 10–20% lotion or cream may increase the efficacy of topical treatments in thick (“moccasin”) tinea of the soles.
Itraconazole, 200 mg daily for 2 weeks or 400 mg daily for 1 week, or terbinafine, 250 mg daily for 2–4 weeks, may be used in refractory cases. If the infection is cleared by systemic therapy, the patient should be encouraged to begin maintenance with topical therapy, since recurrence is common.
For many individuals, tinea pedis is a chronic affliction, temporarily cleared by therapy only to recur.
et al. Oral treatments for fungal infections of the skin of the foot. Cochrane Database Syst Rev. 2012 Oct 17;10:CD003584.
et al. Identifying signs of tinea pedis: a key to understanding clinical variables. J Drugs Dermatol. 2015 Oct;14(10):s42–7.
4. Tinea Versicolor (Pityriasis Versicolor)
ESSENTIALS OF DIAGNOSIS
Velvety, tan, or pink macules or white macules that do not tan with sun exposure.
Fine scales that are not visible but are seen by scraping the lesion.
Central upper trunk the most frequent site.
Yeast and short hyphae observed on microscopic examination of scales.
Tinea versicolor is a mild, superficial Malassezia infection of the skin (usually of the upper trunk). This yeast is a colonizer of all humans, which accounts for the high recurrence rate after treatment. The eruption is often called to patients’ attention by the fact that the involved areas will not tan, and the resulting hypopigmentation may be mistaken for vitiligo. A hyperpigmented form is not uncommon.
Lesions are asymptomatic, but a few patients note itching. The lesions are velvety, tan, pink, or white macules that vary from 4 mm to 5 mm in diameter to large confluent areas (eFigure 6–36) (eFigure 6–53). The lesions initially do not look scaly, but scales may be readily obtained by scraping the area. Lesions may appear on the trunk, upper arms, neck, and groin.
Extensive hypopigmented lesions of tinea versicolor in a black patient. (Used, with permission, from S Goldstein.)
Large, blunt hyphae and thick-walled budding spores (“spaghetti and meatballs”) are seen on KOH (eFigure 6–54). Fungal culture is not useful.
Tinea versicolor diagnosed by KOH preparation. Note short hyphal elements and numerous spores not seen in KOH preparations of true dermatophytes. (Used, with permission, from S Goldstein.)
Vitiligo usually presents with larger periorificial and acral lesions and is also characterized by total (not partial) depigmentation (eFigure 6–55). Vitiligo does not scale. Pink and red-brown lesions on the chest are differentiated from seborrheic dermatitis of the same areas by the KOH preparation (eFigure 6–35).
Vitiligo: depigmented macules. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Topical treatments include selenium sulfide lotion, which may be applied from neck to waist daily and left on for 5–15 minutes for 7 days; this treatment is repeated weekly for a month and then monthly for maintenance. Ketoconazole shampoo, 1% or 2%, lathered on the chest and back and left on for 5 minutes may also be used weekly for treatment and to prevent recurrence. Clinicians must stress to the patient that the raised and scaly aspects of the rash are being treated; the alterations in pigmentation may take months to fade or fill in.
Ketoconazole, 200 mg daily orally for 1 week or 400 mg as a single oral dose, with exercise to the point of sweating after ingestion, results in short-term cure of 90% of cases. Patients should be instructed not to shower for 8–12 hours after taking ketoconazole, because it is delivered in sweat to the skin. The single dose may not work in more hot and humid areas, and more protracted therapy carries a small risk of drug-induced hepatitis. Two doses of oral fluconazole, 300 mg, 14 days apart, has similar efficacy. Without maintenance therapy, recurrences will occur in over 80% of “cured” cases over the subsequent 2 years. Imidazole creams, solutions, and lotions are quite effective for localized areas but are too expensive for use over large areas such as the chest and back.
et al. Systematic review of systemic treatments for tinea versicolor and evidence-based dosing regimen recommendations. J Cutan Med Surg. 2014 Mar–Apr;18(2):79–90.
DISCOID & SUBACUTE LUPUS ERYTHEMATOSUS (CHRONIC CUTANEOUS LUPUS ERYTHEMATOSUS)
ESSENTIALS OF DIAGNOSIS
Localized violaceous red plaques, usually on the face and scalp.
Scaling, follicular plugging, atrophy, dyspigmentation, and telangiectasia of involved areas.
The two most common forms of chronic cutaneous lupus erythematosus (CCLE) are chronic scarring (discoid) lesions (DLE) and erythematous non-scarring red plaques (subacute cutaneous LE) (SCLE) (eFigure 6–56) (eFigure 6–57). Both occur most frequently in photoexposed areas. Permanent hair loss and loss of pigmentation are common sequelae of discoid lesions. Systemic lupus erythematosus (SLE) is discussed in Chapter 20. Patients with SLE may have DLE or SCLE lesions.
Lupus erythematosus: photodistribution. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Discoid lupus erythematosus of the scalp causing scarring, hair loss, and depigmentation. Scaling is seen at the edges of the lesion. (Used, with permission, from S Goldstein.)
Symptoms are usually mild. The lesions consist of violaceous red, well-localized, single or multiple plaques, 5–20 mm in diameter, usually on the head in DLE and the trunk in SCLE. In DLE, the scalp, face, and external ears (conchal bowl) may be involved (eFigure 6–57). In discoid lesions, there is atrophy, telangiectasia, depigmentation, and follicular plugging. On the scalp, significant permanent hair loss may occur in lesions of DLE. In SCLE, the lesions are erythematous annular or psoriasiform plaques up to several centimeters in diameter and favor the upper chest and back.
In patients with DLE, the possibility of SLE should be considered if the following findings are present: positive antinuclear antibody (ANA), other positive serologic studies (eg, anti-double-stranded DNA or anti-Smith antibody), high erythrocyte sedimentation rate, arthralgias/arthritis, presence of hypocomplementemia, widespread lesions (not localized to the head), or nail changes. Patients with marked photosensitivity and a picture otherwise suggestive of lupus may have negative ANA tests but are positive for antibodies against Ro/SSA or La/SSB (SCLE).
The diagnosis is based on the clinical appearance confirmed by skin biopsy in all cases. In DLE, the scales are dry and “thumbtack-like” and can thus be distinguished from those of seborrheic dermatitis and psoriasis (eFigure 6–35) (eFigure 6–22). Older lesions that have left depigmented scarring or areas of hair loss will also differentiate lupus from these diseases. Ten percent of patients with SLE have discoid skin lesions, and 5% of patients with discoid lesions have SLE. Medications (most commonly, hydrochlorothiazide, calcium channel blockers, H2-blockers and proton pump inhibitors, ACE inhibitors, TNF inhibitors, and terbinafine) may induce SCLE with a positive Ro/SSA.
Protect from sunlight. Use high-SPF (more than 50) sunblock with UVB and UVA coverage daily. Caution: do not use any form of radiation therapy. Avoid using medications that are potentially photosensitizing when possible.
For limited lesions, the following should be tried before systemic therapy: high-potency corticosteroid creams applied each night and covered with airtight, thin, pliable plastic film (eg, Saran Wrap); Cordran tape; or ultra–high-potency corticosteroid cream or ointment applied twice daily without occlusion.
Triamcinolone acetonide suspension, 2.5–10 mg/mL, may be injected into the lesions of DLE once a month.
Caution: these medications should be used only when the diagnosis is secure because they have been associated with flares of psoriasis, which may be in the differential diagnosis.
A. Hydroxychloroquine sulfate
0.2–0.4 g orally daily for several months may be effective and is often used prior to chloroquine. A minimum 3-month trial is recommended.
250 mg daily may be effective in some cases where hydroxychloroquine is not.
100 mg daily may be the safest of the antimalarials, since eye damage has not been reported. It colors the skin yellow and is therefore not acceptable to some patients. It may be added to the other antimalarials for patients with incomplete responses.
Isotretinoin, 1 mg/kg/day, is effective in hypertrophic DLE lesions.
Thalidomide is effective in refractory cases in doses of 50–300 mg daily. Monitor for neuropathy.
Both isotretinoin and thalidomide are teratogens and should be used with appropriate contraception and monitoring in women of childbearing age.
The disease is persistent but not life-endangering unless systemic lupus is present. Treatment with one or more antimalarials is effective in more than half of cases. Although the only morbidity may be cosmetic, this can be of overwhelming significance in more darkly pigmented patients with widespread disease. Scarring alopecia can be prevented or lessened with close attention and aggressive therapy. Over years, DLE tends to become inactive. Drug-induced SCLE usually resolves over months when the inciting medication is stopped.
et al. Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus. Br J Dermatol. 2012 Jan;166(1):29–35.
et al. Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden. Br J Dermatol. 2012 Aug;167(2):296–305.
et al. Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus. J Am Acad Dermatol. 2013 Jul;69(1):19–24.
et al. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol. 2013 Jun;27(3):391–404.
et al. Systemic symptoms in the progression of cutaneous to systemic lupus erythematosus. JAMA Dermatol. 2014 Mar;150(3):291–6.
CUTANEOUS T-CELL LYMPHOMA (MYCOSIS FUNGOIDES)
Mycosis fungoides is a cutaneous T-cell lymphoma that begins on the skin and may involve only the skin for years or decades. It may progress to systemic disease, including Sézary syndrome (erythroderma with circulating malignant T cells).
Localized or generalized erythematous scaly patches or plaques are present usually on the trunk. Plaques are almost always over 5 cm in diameter. Pruritus is a frequent complaint and can be severe. IL-31 may mediate the pruritus of Sézary syndrome. The lesions often begin as nondescript or nondiagnostic patches, and it is not unusual for the patient to have skin lesions for more than a decade before the diagnosis can be confirmed. Follicular involvement with hair loss is characteristic of mycosis fungoides, and its presence should raise the suspicion of mycosis fungoides for any pruritic eruption. In more advanced cases, tumors appear. Lymphadenopathy may occur locally or widely. Lymph node enlargement may be due to benign expansion of the node (dermatopathic lymphadenopathy) or by specific involvement with mycosis fungoides.
The skin biopsy remains the basis of diagnosis, though at times numerous biopsies are required before the diagnosis can be confirmed. In more advanced disease, circulating malignant T cells (Sézary cells) can be detected in the blood (T-cell gene rearrangement test). Eosinophilia may be present.
Mycosis fungoides may be confused with psoriasis, a drug eruption (including to serotonin reuptake inhibitors), photoallergy, an eczematous dermatitis, or tinea corporis. Histologic examination can distinguish these conditions.
The treatment of mycosis fungoides is complex. Early and aggressive treatment has not been proven to cure or prevent disease progression. Skin-directed therapies, including topical corticosteroids, topical mechlorethamine, bexarotene gel, and UV phototherapy, are used initially. If the disease progresses, PUVA plus retinoids, PUVA plus interferon, extracorporeal photophoresis, bexarotene, alpha-interferon with or without retinoids, interleukin 12, denileukin, and total skin electron beam treatment are used.
Mycosis fungoides is usually slowly progressive (over decades). Prognosis is better in patients with patch or plaque stage disease and worse in patients with erythroderma, tumors, and lymphadenopathy. Survival is not reduced in patients with limited patch disease. Elderly patients with limited patch and plaque stage disease commonly die of other causes. Overly aggressive treatment may lead to complications and premature demise.
et al. Outcomes after diagnosis of mycosis fungoides and Sézary syndrome before 30 years of age: a population-based study. JAMA Dermatol. 2014 Jul;150(7):709–15.
et al. Recent advances in primary cutaneous T-cell lymphoma. Curr Opin Oncol. 2015 Mar;27(2):128–33.
et al. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014 Feb;70(2):205.e1–16.
et al. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions. J Am Acad Dermatol. 2014 Feb;70(2):223.e1–17.
et al. Changing incidence trends of cutaneous T-cell lymphoma. JAMA Dermatol. 2013 Nov;149(11):1295–9.
et al. Serum IL-31 levels are increased in patients with cutaneous T-cell lymphoma. Acta Derm Venereol. 2012 May;92(3):282–3.
RA. Cutaneous T-cell lymphoma: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014 Aug;89(8):837–51.
EXFOLIATIVE DERMATITIS (EXFOLIATIVE ERYTHRODERMA)
ESSENTIALS OF DIAGNOSIS
Scaling and erythema over most of the body.
Itching, malaise, fever, chills, weight loss.
Erythroderma describes generalized redness and scaling of the skin of more than 30% BSA. A preexisting dermatosis is the cause of exfoliative dermatitis in two-thirds of cases, including psoriasis, atopic dermatitis, contact dermatitis, pityriasis rubra pilaris, and seborrheic dermatitis. Reactions to topical or systemic medications account for about 15% of cases, cancer (underlying lymphoma, solid tumors and, most commonly, cutaneous T-cell lymphoma) for about 10%, and 10% are idiopathic. Widespread scabies is an important diagnostic consideration since patients with erythrodermic presentation are highly contagious. At the time of acute presentation, without a clear-cut prior history of skin disease or medication exposure, it may be impossible to make a specific diagnosis of the underlying condition, and diagnosis may require continued observation.
Symptoms may include itching, weakness, malaise, fever, and weight loss. Chills are prominent. Erythema and scaling are widespread. Loss of hair and nails can occur. Generalized lymphadenopathy may be due to lymphoma or leukemia or may be reactive. The mucosae are typically spared.
A skin biopsy is required and may show changes of a specific inflammatory dermatitis or cutaneous T-cell lymphoma. Peripheral leukocytes may show clonal rearrangements of the T-cell receptor in Sézary syndrome.
It may be impossible to identify the cause of exfoliative erythroderma early in the course of the disease, so careful follow-up is necessary.
Protein and electrolyte loss as well as dehydration may develop in patients with generalized inflammatory exfoliative erythroderma; or sepsis may occur.
Home treatment is with cool to tepid baths and application of mid-potency corticosteroids under wet dressings or with the use of an occlusive plastic suit. If the exfoliative erythroderma becomes chronic and is not manageable in an outpatient setting, the patient should be hospitalized. Keep the room at a constant warm temperature and provide the same topical treatment as for an outpatient.
Stop all medications, if possible. Systemic corticosteroids may provide spectacular improvement in severe or fulminant exfoliative dermatitis, but long-term therapy should be avoided (see Chapter 26). In addition, systemic corticosteroids must be used with caution because some patients with erythroderma have psoriasis and could develop pustular flare. For cases of psoriatic erythroderma and pityriasis rubra pilaris, acitretin, methotrexate, cyclosporine, or a TNF inhibitor may be indicated. Erythroderma secondary to lymphoma or leukemia requires specific topical or systemic chemotherapy. Suitable antibiotic medications with coverage for Staphylococcus should be given when there is evidence of bacterial infection.
Most patients recover completely or improve greatly over time but may require long-term therapy. Deaths are rare in the absence of cutaneous T-cell lymphoma. A minority of patients will suffer from undiminished erythroderma for indefinite periods.
et al. Erythroderma: a clinical and prognostic study. Dermatology. 2012;225(2):154–62.
et al. Erythroderma in the era of biological therapies. Eur J Dermatol. 2012 Mar–Apr;22(2):167–71.
MISCELLANEOUS SCALING DERMATOSES
Isolated scaly patches may represent actinic (solar) keratoses, nonpigmented seborrheic keratoses, or Bowen or Paget disease.
Actinic keratoses are small (0.2–0.6 cm) macules or papules—flesh-colored, pink, or slightly hyperpigmented—that feel like sandpaper and are tender when the finger is drawn over them. They occur on sun-exposed parts of the body in persons of fair complexion. Actinic keratoses are considered premalignant, but only 1:1000 lesions per year progress to become squamous cell carcinomas.
Application of liquid nitrogen is a rapid method of eradication. The lesions crust and disappear in 10–14 days. “Field treatment” with a topical agent to the anatomic area where the actinic keratoses are most prevalent (eg, forehead, dorsal hands, etc) can be considered in patients with multiple lesions in one region. The topical agents used for field treatment include fluorouracil, imiquimod, and ingenol mebutate. Photodynamic therapy can be effective in cases refractory to topical treatment. Any lesions that persist should be evaluated for possible biopsy.
et al. Efficacy of photodynamic therapy vs other interventions in randomized clinical trials for the treatment of actinic keratoses: a systematic review and meta-analysis. JAMA Dermatol. 2014 Dec;150(12):1281–8.
et al. Evidence- and consensus-based (S3) guidelines for the treatment of actinic keratosis – International League of Dermatological Societies in cooperation with the European Dermatology Forum – short version. J Eur Acad Dermatol Venereol. 2015 Nov;29(11):2069–79.
et al. The natural history of actinic keratosis: a systematic review. Br J Dermatol. 2013 Sep;169(3):502–18.
2. Bowen Disease & Paget Disease
Bowen disease (intraepidermal squamous cell carcinoma) can develop on both sun-exposed and non–sun-exposed skin. The lesion is usually a small (0.5–3 cm), well-demarcated, slightly raised, pink to red, scaly plaque and may resemble psoriasis or a large actinic keratosis (eFigure 6–58). These lesions may progress to invasive squamous cell carcinoma. Excision or other definitive treatment is indicated.
This isolated, scaly patch on a patient's arm turned out to be Bowen disease (intraepidermal squamous cell carcinoma) on biopsy. (Used, with permission, from S Goldstein.)
Extramammary Paget disease, a manifestation of intraepidermal carcinoma or underlying genitourinary or gastrointestinal cancer, resembles chronic eczema and usually involves apocrine areas such as the genitalia. Mammary Paget disease of the nipple, a unilateral or rarely bilateral red scaling plaque that may ooze, is associated with an underlying intraductal mammary carcinoma (Figure 6–13). While these lesions appear as red patches and plaques in fair-skinned persons, in darker-skinned individuals, hyperpigmentation may be prominent.
Paget disease of the breast surrounding the nipple. (From the University of Texas Health Sciences Center, Division of Dermatology; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
et al. Interventions for cutaneous Bowen’s disease. Cochrane Database Syst Rev. 2013 Jun 24;6:CD007281.
et al. Interventions for the treatment of Paget’s disease of the vulva. Cochrane Database Syst Rev. 2013 Oct 26;10:CD009245.
et al. British Association of Dermatologists’ guidelines for the management of squamous cell carcinoma in situ (Bowen’s disease) 2014. Br J Dermatol. 2014 Feb;170(2):245–60.
Intertrigo is caused by the macerating effect of heat, moisture, and friction. It is especially likely to occur in obese persons and in humid climates. The symptoms are itching, stinging, and burning. The body folds develop fissures, erythema, and sodden epidermis, with superficial denudation (eFigure 6–27). Candidiasis may complicate intertrigo (eFigure 6–45) (eFigure 6–59). “Inverse psoriasis,” (eFigure 6–46) seborrheic dermatitis, tinea cruris, erythrasma (eFigure 6–47), and candidiasis must be ruled out.
Candidal intertrigo. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Maintain hygiene in the area, and keep it dry. Compresses may be useful acutely. Hydrocortisone 1% cream plus an imidazole or clotrimazole 1% cream is effective. Recurrences are common.
et al. Intertrigo and secondary skin infections. Am Fam Physician. 2014 Apr 1;89(7):569–73.
HERPES SIMPLEX (COLD OR FEVER SORE; GENITAL HERPES)
ESSENTIALS OF DIAGNOSIS
Recurrent small grouped vesicles on an erythematous base, especially in the orolabial and genital areas.
May follow minor infections, trauma, stress, or sun exposure; regional lymph nodes may be swollen and tender.
Viral cultures and direct fluorescent antibody tests are positive.
Over 85% of adults have serologic evidence of herpes simplex type 1 (HSV-1) infections, most often acquired asymptomatically in childhood. Occasionally, primary infections may be manifested as severe gingivostomatitis. Thereafter, the patient may have recurrent self-limited attacks, provoked by sun exposure, orofacial surgery, fever, or a viral infection.
About 25% of the United States population has serologic evidence of infection with herpes simplex type 2 (HSV-2). HSV-2 causes lesions whose morphology and natural history are similar to those caused by HSV-1 but are typically located on the genitalia of both sexes. The infection is acquired by sexual contact. In monogamous heterosexual couples where one partner has HSV-2 infection, seroconversion of the noninfected partner occurs in 10% over a 1-year period. Up to 70% of such infections appeared to be transmitted during periods of asymptomatic shedding. Genital herpes may also be due to HSV-1.
The principal symptoms are burning and stinging. Neuralgia may precede or accompany attacks. The lesions consist of small, grouped vesicles that can occur anywhere but which most often occur on the vermilion border of the lips (eFigure 6–60) and (Figure 6–14), the penile shaft, the labia, the perianal skin, and the buttocks (eFigure 6–61) (eFigure 6–62). Any erosion or fissure in the anogenital region can be due to herpes simplex. Regional lymph nodes may be swollen and tender. The lesions usually crust and heal in 1 week. Immunosuppressed patients may have unusual variants, including verrucous or nodular herpes lesions at typical sites of involvement.
Herpes simplex type 1 vesicles at the vermillion border of the lip. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Herpes simplex. (Used, with permission, from Berger TG, Dept. Dermatology, UCSF.)
Multiple oral ulcerations (herpes simplex). (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Primary herpetic stomatitis with clusters of punched-out geometric erosions on the tongue and pharynx. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Lesions of herpes simplex must be distinguished from chancroid, syphilis, pyoderma, or trauma. Direct fluorescent antibody slide tests offer rapid, sensitive diagnosis. Viral culture may also be helpful. Herpes serology is not used in the diagnosis of an acute genital ulcer. However, specific HSV-2 serology by Western blot assay or enzyme-linked immunosorbent assay (ELISA) can determine who is HSV-infected and potentially infectious. Such testing is very useful in couples in which only one partner reports a history of genital herpes.
Complications include pyoderma, eczema herpeticum, herpetic whitlow (eFigure 6–63), herpes gladiatorum (epidemic herpes in wrestlers transmitted by contact), proctitis, esophagitis, neonatal infection, keratitis, and encephalitis.
Herpetic whitlow with large pustules superimposed on erythema and edema of the finger. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Three systemic agents are available for the treatment of herpes infections: acyclovir, its valine analog valacyclovir, and famciclovir. All three agents are very effective, and when used properly, virtually nontoxic. Only acyclovir is available for intravenous administration. In the immunocompetent, with the exception of severe orolabial herpes, only genital disease is treated. For first clinical episodes of herpes simplex, the dosage of acyclovir is 400 mg orally five times daily (or 800 mg three times daily); of valacyclovir, 1000 mg twice daily; and of famciclovir, 250 mg three times daily. The duration of treatment is from 7 to 10 days depending on the severity of the outbreak.
Most cases of recurrent herpes are mild and do not require therapy. In addition, pharmacotherapy of recurrent HSV is of limited benefit, with studies finding a reduction in the average outbreak by only 12–24 hours. To be effective, the treatment must be initiated by the patient at the first sign of recurrence. If treatment is desired, recurrent genital herpes outbreaks may be treated with 3 days of valacyclovir, 500 mg twice daily, 5 days of acyclovir, 200 mg five times a day, or 5 days of famciclovir, 125 mg twice daily. Valacyclovir, 2 g twice daily for 1 day, or famciclovir, 1 g once or twice in 1 day, are equally effective short-course alternatives and can abort impending recurrences of both orolabial and genital herpes. The addition of a potent topical corticosteroid three times daily reduces the duration, size, and pain of orolabial herpes treated with an oral antiviral agent.
In patients with frequent or severe recurrences, suppressive therapy may be effective in controlling disease. Suppressive treatment will reduce outbreaks by 85% and reduces viral shedding by more than 90%. This results in about a 50% reduced risk of transmission. The recommended suppressive doses, taken continuously, are acyclovir, 400 mg twice daily; valacyclovir, 500 mg once daily; or famciclovir, 125–250 mg twice daily. Long-term suppression appears very safe, and after 5–7 years a substantial proportion of patients can discontinue treatment.
The use of latex condoms and patient education have proved effective in reducing genital herpes transmission in some studies but have not proved beneficial in others. No single or combination intervention absolutely prevents transmission. Sunscreens are useful adjuncts in preventing sun-induced HSV-1 recurrences. A preventive antiviral medication should be started beginning 24 hours prior to ultraviolet light exposure, dental surgery, or orolabial cosmetic surgery.
In general, topical therapy has only limited efficacy and is generally not recommended because evidence shows that it only minimally reduces skin healing time.
Aside from the complications described above, recurrent attacks last several days, and patients recover without sequelae.
et al. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients. Cochrane Database Syst Rev. 2014 Aug 3;8:CD009036.
et al. Patterns of disease and treatment of cold sores. J Dermatolog Treat. 2013 Dec;24(6):439–43.
ESSENTIALS OF DIAGNOSIS
Pain along the course of a nerve followed by grouped vesicular lesions.
Involvement is unilateral; some lesions (fewer than 20) may occur outside the affected dermatome.
Lesions are usually on face or trunk.
Direct fluorescent antibody positive, especially in vesicular lesions.
Herpes zoster is an acute vesicular eruption due to the varicella-zoster virus. It usually occurs in adults and incidence rises with age. With rare exceptions, patients suffer only one attack. While dermatomal herpes zoster is common, generalized disease raises the suspicion of an associated immunosuppressive disorder, such as HIV infection. HIV-infected patients are 20 times more likely to develop zoster, often before other clinical findings of HIV disease are present. A history of HIV risk factors and HIV testing when appropriate should be considered, especially in patients with zoster who are younger than 55 years.
Pain usually precedes the eruption by 48 hours or more and may persist after the lesions have disappeared. The lesions consist of grouped, tense, deep-seated vesicles distributed unilaterally along a dermatome (Figure 6–15) (eFigure 6–64). The most common distributions are on the trunk or face. Up to 20 lesions may be found outside the affected dermatomes, even in immune-competent persons. Regional lymph nodes may be tender and swollen.
Herpes zoster. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Clusters of umbilicated herpes zoster vesicles erupt in linear, dermatomal patterns. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Since poison oak and poison ivy dermatitis can occur unilaterally, they must be differentiated at times from herpes zoster (eFigure 6–65). Allergic contact dermatitis is pruritic; zoster is painful. One must differentiate herpes zoster from lesions of herpes simplex, which rarely occurs in a dermatomal distribution. Doses of antivirals appropriate for zoster should be used in the absence of a clear diagnosis. Facial zoster may simulate erysipelas initially, but zoster is unilateral and shows vesicles after 24–48 hours. Depending on the dermatome involved, the pain of preeruptive herpes zoster may lead the clinician to diagnose migraine, myocardial infarction, acute abdomen, herniated disk, etc.
Poison oak. Note the linear streaky distribution of lesions. (Used, with permission, from S Goldstein.)
Sacral zoster may be associated with bladder and bowel dysfunction. Persistent neuralgia, anesthesia or scarring of the affected area, facial or other nerve paralysis, and encephalitis may occur. Postherpetic neuralgia is most common after involvement of the trigeminal region and in patients over the age of 55. Early (within 72 hours after onset) and aggressive antiviral treatment of herpes zoster reduces the severity and duration of postherpetic neuralgia. Zoster ophthalmicus (V1) can result in visual impairment. Increased risk of transient ischemic attack and stroke has been demonstrated.
An effective live herpes zoster vaccine (Zostavax) is available and recommended to prevent both herpes zoster and postherpetic neuralgia. It is approved for persons over the age of 50 and recommended in persons aged 60 and older, even in those who have had zoster.
Antiviral treatment within 72 hours of rash decreases the duration and severity of acute herpes zoster. Since such treatment also reduces postherpetic neuralgia, those with a risk of developing this complication should be treated (ie, those over age 50 and those with nontruncal eruption). In addition, patients with acute moderate to severe pain or rash may benefit from antiviral therapy. Treatment can be given with oral acyclovir, 800 mg five times daily; famciclovir, 500 mg three times daily; or valacyclovir, 1 g three times daily—all for 7 days (see Chapter 32). For reasons of increased bioavailability and ease of dosing schedule, the preferred agents are those given three times daily. Patients should maintain good hydration. The dose of antiviral should be adjusted for kidney function as recommended. Nerve blocks may be used in the management of initial severe pain. Ophthalmologic consultation is vital for involvement of the first branch of the trigeminal nerve, even if the patient has no ocular symptoms.
Systemic corticosteroids are effective in reducing acute pain, improving quality of life, and returning patients to normal activities much more quickly. They do not increase the risk of dissemination in immunocompetent hosts. If not contraindicated, a tapering 3-week course of prednisone, starting at 60 mg/day, should be considered for its adjunctive benefit in immunocompetent patients. Oral corticosteroids do not reduce the prevalence, severity, or duration of postherpetic neuralgia beyond that achieved by effective antiviral therapy. Adequate analgesia, including the use of opioids, tricyclic antidepressants, and gabapentin as necessary, should be given for zoster-associated pain.
2. Immunocompromised host
Given the safety and efficacy of currently available antivirals, most immunocompromised patients with herpes zoster are candidates for antiviral therapy. The dosage schedule is as listed above, but treatment should be continued until the lesions have completely crusted and are healed or almost healed (up to 2 weeks). Because corticosteroids increase the risk of dissemination in immunosuppressed patients, they should not be used in these patients. Progression of disease may necessitate intravenous therapy with acyclovir, 10 mg/kg intravenously, three times daily. After 3–4 days, oral therapy may be substituted if there has been a good response to intravenous therapy. Adverse effects include decreased kidney function from crystallization, nausea and vomiting, and abdominal pain.
Foscarnet, administered in a dosage of 40 mg/kg two or three times daily intravenously, is indicated for treatment of acyclovir-resistant varicella-zoster virus infections.
Calamine or aluminum salt compresses (Domeboro, Burow soaks) may be helpful for dry weeping lesions.
C. Postherpetic Neuralgia Therapy
The most effective treatment is prevention with vaccination of those at risk for developing zoster and early and aggressive antiviral therapy once zoster has occurred. Once established, postherpetic neuralgia may be treated with capsaicin ointment, 0.025–0.075%, or lidocaine (Lidoderm) topical patches. Chronic postherpetic neuralgia may be relieved by regional blocks (stellate ganglion, epidural, local infiltration, or peripheral nerve), with or without corticosteroids added to the injections. Tricyclic antidepressants, such as amitriptyline, 25–75 mg orally as a single nightly dose, are the first-line therapy beyond simple analgesics. Gabapentin, up to 3600 mg orally daily (starting at 300 mg orally three times daily), or duloxetine, up to 60–120 mg orally daily (starting at 30–60 mg orally daily) may be added for additional pain relief. Long-acting opioids may be appropriate. Referral to a pain management clinic should be considered in moderate to severe cases and in those who do not respond to the above treatments.
The eruption persists 2–3 weeks and usually does not recur. Motor involvement in 2–3% of patients may lead to temporary palsy.
et al. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. Neurology. 2014 Jul 8;83(2):e27–33.
et al. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2012 Oct 17;10:CD008858.
et al. Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526–33.
et al. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open. 2014 Jun 10;4(6):e004833.
et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087–96.
et al. Vaccines for post-exposure prophylaxis against varicella in children and adults. Cochrane Database Syst Rev. 2014 Jun 23:6:CD001833.
VARIOLA (SMALLPOX) & VACCINIA
ESSENTIALS OF DIAGNOSIS
Prodromal high fever.
Eruption progressing from papules to vesicles to pustules, then crusts.
All lesions in the same stage.
Face and distal extremities (including palms and soles) favored.
Concern for the use of smallpox virus as a bioterrorist weapon has led to the reintroduction of vaccination in some segments of the population (first responders and the military).
The incubation period for variola averages 12 days (7–17 days). The prodrome begins with abrupt onset of high fever, severe headaches, and backaches. At this stage, the infected person appears quite ill. The infectious phase begins with the appearance of an exanthem, followed in 1–2 days by a skin eruption. The lesions begin as macules, progressing to papules, then pustules, and finally crusts over 14–18 days. The face and distal extremities are favored. The face is affected first, followed by the upper extremities, then the lower extremities and trunk, completely evolving over 1 week. Lesions are relatively monomorphous, especially in each anatomic region.
Inoculation with vaccinia produces a papular lesion on day 2–3 that progresses to an umbilicated papule by day 4 and a pustular lesion by the end of the first week. The lesion then collapses centrally, and crusts. The crust eventually detaches up to a month after the inoculation. Persons with eczema should not be immunized because widespread vaccinia (eczema vaccinatum), which might resemble the lesions of smallpox, may develop. Vaccinia is moderately contagious, and patients with atopic dermatitis and Darier disease may acquire severe generalized disease by exposure to a recently vaccinated person. Generalized vaccinia may be fatal. Prior vaccination does not prevent generalized vaccinia, but previously vaccinated individuals have milder disease. Progressive vaccinia (vaccinia gangrenosum)—progression of the primary inoculation site to a large ulceration—occurs in persons with systemic immune deficiency. It can have a fatal outcome.
Smallpox and vaccinia are to be distinguished from generalized varicella zoster virus infection or generalized herpes simplex. The latter two viral infections are not associated with a severe febrile prodrome. Lesions are at various stages at each anatomic site. Varicella usually appears in waves or crops. Multiple palm and sole lesions are common in variola and uncommon in generalized varicella-zoster and herpes simplex infection.
Direct fluorescent antibody testing for HSV and varicella zoster virus are the first-line diagnostic tests to differentiate varicella zoster virus, HSV, vaccinia, and variola. Until the diagnosis is confirmed, strict isolation of the patient is indicated. Similar fluorescent testing for variola can be performed in special laboratories.
There is no specific and proven antiviral therapy for vaccinia or variola. Vaccinia immune globulin is used to treat eczema vaccinatum and progressive vaccinia. Cidofovir may have some activity against these poxviruses.
POMPHOLYX; VESICULOBULLOUS HAND ECZEMA (FORMERLY KNOWN AS DYSHIDROSIS, DYSHIDROTIC ECZEMA)
ESSENTIALS OF DIAGNOSIS
Pruritic “tapioca” vesicles of 1–2 mm on the palms, soles, and sides of fingers.
Vesicles may coalesce to form multiloculated blisters.
Scaling and fissuring may follow drying of the blisters.
Appearance in the third decade, with lifelong recurrences.
This is an extremely common form of hand dermatitis, preferably called pompholyx (Gr “bubble”) or vesiculobullous dermatitis of the palms and soles. About half of patients have an atopic background, and many patients report flares with stress. Patients with widespread dermatitis due to any cause may develop pompholyx-like eruptions as a part of an autoeczematization response.
Small clear vesicles stud the skin at the sides of the fingers and on the palms (Figure 6–16) (eFigure 6–51) or soles. They look like the grains in tapioca. They may be associated with intense itching. Later, the vesicles dry and the area becomes scaly and fissured.
Pompholyx (acute vesiculobullous hand eczema). (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Unroofing the vesicles and examining the blister roof with a KOH preparation will reveal hyphae in cases of bullous tinea. Always examine the feet of a patient with a hand eruption because patients with inflammatory tinea pedis may have a vesicular autoeczematization of the palms. Nonsteroidal anti-inflammatory drugs (NSAIDs) may produce an eruption very similar to that of dyshidrosis on the hands.
There is no known way to prevent attacks if the condition is idiopathic. About one-third to one-half of patients with vesiculobullous hand dermatitis have a relevant contact allergen, especially nickel. Patch testing and avoidance of identified allergens can lead to improvement.
Topical and systemic corticosteroids help some patients dramatically. Since this is a chronic problem, systemic corticosteroids are generally not appropriate therapy. A high-potency topical corticosteroid used early in the attack may help abort the flare and ameliorate pruritus. Topical corticosteroids are also important in treating the scaling and fissuring that are seen after the vesicular phase. It is essential that patients avoid anything that irritates the skin; they should wear cotton gloves inside vinyl gloves when doing dishes or other wet chores, use long-handled brushes instead of sponges, and use a hand cream after washing the hands. Patients respond to PUVA therapy and injection of botulinum toxin into the palms as for hyperhidrosis.
For most patients, the disease is an inconvenience. For some, vesiculobullous hand eczema can be incapacitating.
et al. Characteristics and provision of care in patients with chronic hand eczema: updated data from the CARPE Registry. Acta Derm Venereol. 2014 Feb 26;94(2):163–7.
et al. Hand dermatitis: review of clinical features and treatment options. Semin Cutan Med Surg. 2013 Sep;32(3):147–57.
et al. Hand dermatitis: an allergist’s nightmare. Curr Allergy Asthma Rep. 2014 Nov;14(11):474.
ESSENTIALS OF DIAGNOSIS
Noninflammatory blisters on sun-exposed sites, especially the dorsal surfaces of the hands.
Hypertrichosis, skin fragility.
Associated liver disease.
Elevated urine porphyrins.
Porphyria cutanea tarda is the most common type of porphyria. Cases are sporadic or hereditary. The disease is associated with ingestion of certain medications (eg, estrogens) and liver disease from alcoholism, hemochromatosis, or hepatitis C.
Patients complain of painless blistering and fragility of the skin of the dorsal surfaces of the hands (Figure 6–17). Facial hypertrichosis and hyperpigmentation are common.
Porphyria cutanea tarda. (From Lewis Rose, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Urinary uroporphyrins are elevated twofold to fivefold above coproporphyrins. Patients may also have abnormal liver function tests, evidence of hepatitis C infection, increased liver iron stores, and hemochromatosis gene mutations.
Skin lesions identical to those of porphyria cutanea tarda may be seen in patients who undergo dialysis and in those who take certain medications (tetracyclines, voriconazole, and NSAIDs, especially naproxen). In this so-called pseudoporphyria, the biopsy results are identical to those associated with porphyria cutanea tarda, but urine porphyrins are normal.
Barrier sun protection with clothing is required. Although the lesions are triggered by sun exposure, the wavelength of light triggering the lesions is beyond that absorbed by sunscreens.
Stopping all triggering medications and substantially reducing or stopping alcohol consumption may alone lead to improvement. Phlebotomy without oral iron supplementation at a rate of 1 unit every 2–4 weeks will gradually lead to improvement. Very low-dose antimalarial medication (as low as 200 mg of hydroxychloroquine twice weekly), alone or in combination with phlebotomy, will increase the excretion of porphyrins, improving the skin disease. Deferasirox, an iron chelator can also improve porphyria cutanea tarda. Treatment is continued until the patient is asymptomatic. Urine porphyrins may be monitored.
Most patients improve with treatment. Sclerodermoid skin lesions may develop on the trunk, scalp, and face.
Dermatitis herpetiformis is an uncommon disease manifested by pruritic papules, vesicles, and papulovesicles mainly on the elbows, knees, buttocks, posterior neck, and scalp (eFigure 6–66) (eFigure 6–67). It appears to have its highest prevalence in Northern Europe and is associated with HLA antigens -B8, -DR3, and -DQ2. The histopathology is distinctive. Circulating antibodies to tissue transglutaminase are present in 90% of cases. NSAIDs may cause flares. Patients have gluten-sensitive enteropathy, but it is subclinical in the great majority. However, ingestion of gluten is the cause of the disease, and strict long-term avoidance of dietary gluten has been shown to decrease the dose of dapsone (usually 100–200 mg daily) required to control the disease and may even eliminate the need for treatment. Patients with dermatitis herpetiformis are at increased risk for development of gastrointestinal lymphoma, and this risk is reduced by a gluten-free diet.
Dermatitis herpetiformis presenting typically as pruritic papulovesicles on this Scandinavian man's elbow. (Used, with permission, from J Reeves.)
A: Dermatitis herpetiformis. Typical distribution of lesions on the buttocks, shoulders, and elbows. The erythematous infiltrated nature of the lesions with small crusted erosions (scratching!) is apparent. B: Dermatitis herpetiformis (detail). Herpetiform grouping of vesicles on an erythematous base and small crusted erosions. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
et al. Management of dermatitis herpetiformis. Immunol Allergy Clin North Am. 2012 May;32(2):275–81.
et al. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014 Nov–Dec;89(6):865–75.
WEEPING OR CRUSTED LESIONS
ESSENTIALS OF DIAGNOSIS
Superficial blisters filled with purulent material that rupture easily.
Crusted superficial erosions.
Positive Gram stain and bacterial culture.
Impetigo is a contagious and autoinoculable infection of the skin (epidermis) caused by staphylococci or streptococci.
The lesions consist of macules, vesicles, bullae, pustules, and honey-colored crusts that when removed leave denuded red areas (Figure 6–18). The face and other exposed parts are most often involved. Ecthyma is a deeper form of impetigo caused by staphylococci or streptococci, with ulceration and scarring (eFigure 6–68) that occurs frequently on the extremities.
Bullous impetigo. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Ecthyma, shown here, represents a deeper form of impetigo caused by Staphylococcus aureus or streptococci. (Used, with permission, from S Goldstein.)
Gram stain and culture confirm the diagnosis. In temperate climates, most cases are associated with S aureus infection. Streptococcus species are more common in tropical infections.
The main differential diagnoses are acute allergic contact dermatitis (eFigure 6–69) and herpes simplex. Contact dermatitis may be suggested by the history or by linear distribution of the lesions, and culture should be negative for staphylococci and streptococci. Herpes simplex infection usually presents with grouped vesicles or discrete erosions and may be associated with a history of recurrences. Viral cultures are positive.
Poison ivy: fine vesicles in a linear pattern. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Soaks and scrubbing can be beneficial, especially in unroofing lakes of pus under thick crusts. Topical agents, such as bacitracin, mupirocin, and retapamulin, are first-line treatment options for infections limited to small areas. In widespread cases, systemic antibiotics are indicated. Cephalexin, 250 mg four times daily, is usually effective. Doxycycline, 100 mg twice daily, is a reasonable alternative. Community-associated methicillin-resistant S aureus (CA-MRSA) may cause impetigo, and initial coverage for MRSA could include doxycycline or trimethoprim-sulfamethoxazole (TMP-SMZ). About 50% of CA-MRSA cases are quinolone resistant. Recurrent impetigo is associated with nasal carriage of S aureus and is treated with rifampin, 600 mg daily for 5 days. Intranasal mupirocin ointment twice daily for 5 days clears the carriage of 40% of MRSA strains. Bleach baths (¼ to ½ cup per 20 liters of bathwater for 15 minutes 3–5 times weekly) for all family members, and the use of dilute household bleach to clean showers and other bath surfaces may help reduce the spread. Individuals should not share towels if there is a case of impetigo in the household.
et al. Impetigo: diagnosis and treatment. Am Fam Physician. 2014 Aug 15;90(4):229–35.
et al. Interventions for impetigo. Cochrane Database Syst Rev. 2012 Jan 18;1:CD003261.
ESSENTIALS OF DIAGNOSIS
Erythema and edema, with pruritus, often followed by vesicles, bullae, weeping or crusting in an area of contact with a suspected agent.
A history of previous reaction to suspected contactant.
Positive patch test (in allergic contact dermatitis).
Contact dermatitis (irritant or allergic) is an acute or chronic dermatitis that results from direct skin contact with chemicals or allergens. Eighty percent of cases are due to excessive exposure to or additive effects of universal irritants (eg, soaps, detergents, organic solvents) and are called irritant contact dermatitis. This appears red and scaly but not vesicular and occurs only in the direct sites of contact with the irritant. The most common causes of allergic contact dermatitis are poison ivy or poison oak, topically applied antimicrobials (especially bacitracin and neomycin), anesthetics (benzocaine), hair-care products, preservatives, jewelry (nickel), rubber, essential oils, propolis (from bees), vitamin E, and adhesive tape. Occupational exposure is an important cause of allergic contact dermatitis. Weeping and crusting are typically due to allergic and not irritant dermatitis; lesions may also occur slightly outside of contact sites, distinguishing it from irritant dermatitis.
In allergic contact dermatitis, the acute phase is characterized by tiny vesicles and weepy and crusted lesions, whereas resolving or chronic contact dermatitis presents with scaling, erythema, and possibly thickened skin. Itching, burning, and stinging may be severe. The lesions, distributed on exposed parts or in bizarre asymmetric patterns, consist of erythematous macules, papules, and vesicles. The affected area is often hot and swollen, with exudation and crusting, simulating—and at times complicated by—infection. The pattern of the eruption may be diagnostic (eg, typical linear streaked vesicles on the extremities in poison oak or ivy dermatitis [Figure 6–19]) [eFigure 6–65] [eFigure 6–50] [eFigure 6–69]. The location will often suggest the cause: Scalp involvement suggests hair dyes or shampoos; face involvement, creams, cosmetics, soaps, shaving materials, nail polish; and neck involvement, jewelry, hair dyes.
Contact dermatitis with linear pattern due to poison ivy. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Gram stain and culture will rule out impetigo or secondary infection (impetiginization). If itching is generalized, then scabies should be considered. After the episode of allergic contact dermatitis has cleared, patch testing may be useful if the triggering allergen is not known.
Asymmetric distribution, blotchy erythema around the face, linear lesions, and a history of exposure help distinguish acute contact dermatitis from other skin lesions. The most commonly mistaken diagnosis is impetigo (eFigure 6–14) or cellulitis. Chronic allergic contact dermatitis must be differentiated from scabies (eFigure 6–52), atopic dermatitis (eFigure 6–11), and pompholyx (eFigure 6–51).
Prompt and thorough removal of the causative oil by washing with liquid soap may be effective if done within 30 minutes after exposure to poison oak or ivy. Goop and Tecnu are also effective but much more costly without increased efficacy. The three most effective over-the-counter barrier creams that are applied prior to exposure and prevent/reduce the severity of the dermatitis are Stokogard, Hollister Moisture Barrier, and Hydropel.
The mainstay of prevention is identification of the agent causing the dermatitis and avoidance of exposure or use of protective clothing and gloves. In industry-related cases, prevention may be accomplished by moving or retraining the worker.
While local measures are important, severe or widespread involvement is difficult to manage without systemic corticosteroids because even the highest-potency topical corticosteroids seem not to work well on vesicular and weepy lesions. Localized involvement (except on the face) can often be managed solely with topical agents. Irritant contact dermatitis is treated by protection from the irritant and use of topical corticosteroids as for atopic dermatitis (described above). The treatment of allergic contact dermatitis is detailed below.
1. Acute weeping dermatitis
Compresses are most often used. Gentle cleansing is recommended. Calamine lotion or zinc oxide paste may be used between wet dressings, especially for involvement of intertriginous areas or when oozing is not marked. Lesions on the extremities may be bandaged with wet dressings for 30–60 minutes several times a day. High-potency topical corticosteroids in gel or cream form (eg, fluocinonide, clobetasol, or halobetasol) may help suppress acute contact dermatitis and relieve itching. This treatment should be followed by tapering of the number of applications per day or use of a mid-potency corticosteroid, such as triamcinolone 0.1% cream to prevent rebound of the dermatitis. A soothing formulation is 2 oz of 0.1% triamcinolone acetonide cream in 7.5 oz Sarna lotion (0.5% camphor, 0.5% menthol, 0.5% phenol) mixed by the patient.
2. Subacute dermatitis (subsiding)
Mid-potency (triamcinolone 0.1%) to high-potency corticosteroids (clobetasol, fluocinonide, desoximetasone) are the mainstays of therapy.
3. Chronic dermatitis (dry and lichenified)
High-potency to superpotency corticosteroids are used in ointment form. Occlusion may be helpful on the hands.
For acute severe cases, prednisone may be given orally for 12–21 days. Prednisone, 60 mg for 4–7 days, 40 mg for 4–7 days, and 20 mg for 4–7 days without a further taper is one useful regimen. Another is to dispense seventy-eight 5-mg pills to be taken 12 the first day, 11 the second day, and so on. The key is to use enough corticosteroid (and as early as possible) to achieve a clinical effect and to taper slowly enough to avoid rebound. A Medrol Dosepak (methylprednisolone) with 5 days of medication is inappropriate on both counts. (See Chapter 26.)
Allergic contact dermatitis is self-limited if reexposure is prevented but often takes 2–3 weeks for full resolution. Removal of the causative agent is paramount to avoid recurrences.
DL. Occupational skin allergies: testing and treatment (the case of occupational allergic contact dermatitis). Curr Allergy Asthma Rep. 2014 Feb;14(2):410.
ESSENTIALS OF DIAGNOSIS
The most common of all skin conditions.
Almost universal in puberty, though onset may begin in premenarchal girls and present or persist into the fourth or fifth decade.
Comedones are the hallmark of acne vulgaris. Severity varies from purely comedonal to papular or pustular inflammatory acne to cysts or nodules.
Face and upper trunk may be affected.
Scarring may be a sequela of the disease or picking by the patient.
Acne vulgaris is polymorphic. Open and closed comedones, papules, pustules, and cysts are found.
In younger persons, acne vulgaris is more common and more severe in males. It does not always clear spontaneously when maturity is reached. Twelve percent of women and 3% of men over age 25 have acne vulgaris. This rate does not decrease until the fourth or fifth decade of life. The skin lesions parallel sebaceous activity. Pathogenic events include plugging of the infundibulum of the follicles, retention of sebum, overgrowth of the acne bacillus (Propionibacterium acnes) with resultant release of and irritation by accumulated fatty acids, and foreign-body reaction to extrafollicular sebum. The mechanism of antibiotics in controlling acne is not clearly understood, but they may work because of their antibacterial or anti-inflammatory properties.
When a resistant case of acne is encountered in a woman, hyperandrogenism may be suspected. This may or may not be accompanied by hirsutism, irregular menses, or signs of virilism. Polycystic ovary syndrome (PCOS) is the most common identifiable cause.
There may be mild tenderness, pain, or itching. The lesions occur mainly over the face, neck, upper chest, back, and shoulders. Comedones (tiny, flesh-colored, white or black noninflamed superficial papules that give the skin a rough texture or appearance) are the hallmark of acne vulgaris. Inflammatory papules, pustules, ectatic pores, acne cysts, and scarring are also seen (Figure 6–20) (eFigure 6–70).
Acne vulgaris, severe nodular cystic form with scarring. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Acne vulgaris. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Acne may have different presentations at different ages. Preteens often present with comedones as their first lesions. Inflammatory lesions in young teenagers are often found in the middle of the face, extending outward as the patient becomes older. Women in their third and fourth decades (often with no prior history of acne) commonly present with papular lesions on the chin and jawline.
In adults, rosacea presents with papules and pustules in the middle third of the face, but absence of truncal involvement, telangiectasia, flushing, and the absence of comedones distinguish rosacea from acne vulgaris (eFigure 6–71). A pustular eruption on the face in patients receiving antibiotics or with otitis externa should be investigated with culture to rule out an uncommon gram-negative folliculitis. Acne may develop in patients who use systemic corticosteroids or topical fluorinated corticosteroids on the face. Acne may be exacerbated or caused by cosmetic creams or oils. Pustules on the face can also be caused by tinea infections. Lesions on the back are more problematic. When they occur alone, staphylococcal folliculitis, miliaria (“heat rash”) or, uncommonly, Malassezia (Pityrosporum) folliculitis should be suspected. Bacterial culture, trial of an antistaphylococcal antibiotic, and observing the response to therapy will help in the differential diagnosis. In patients with HIV infection, folliculitis is common and may be either staphylococcal folliculitis or eosinophilic folliculitis (typically pruritic tumid papules on the face and neck).
Prominent rhinophyma in a patient with rosacea results from hyperplasia of soft tissues and glands of the nose. (Used, with permission, from K Zipperstein.)
Cyst formation, pigmentary changes, scarring, and poor quality of life may result (eFigure 6–72).
Cystic acne associated with scarring. (Used, with permission, from S Goldstein.)
1. Education of the patient
Education on proper use of medications and cosmetics is paramount. Because lesions take 4–6 weeks to improve, clinical improvement should be measured by the number of new lesions forming after 6–8 weeks of therapy. Additional time (3–4 months) will be required to see improvement on the back and chest, as these areas are slowest to respond. Avoid topical exposure to oils, cocoa butter (theobroma oil), and greases in cosmetics, including hair products. When scarring seems out of proportion to the severity of the lesions, clinicians must suspect that the patient is manipulating the lesions. It is essential that the patient be educated in a supportive way about this complication. Anxiety and depression are common in patients with excoriated acne.
A low glycemic diet has been associated with improvement and lower incidence of acne. This improvement was associated with a reduction in insulin resistance. Hyperinsulinemia has also been associated with acne in both eumenorrheic women and individuals with PCOS. This finding suggests a possible common pathogenic mechanism for acne in both adult women and men.
Treatment of acne is based on the type and severity of lesions. Comedones require treatment different from that of pustules and cystic lesions. In assessing severity, take the sequelae of the lesions into account. An individual who gets only a few new lesions per month that scar or leave postinflammatory hyperpigmentation must be treated much more aggressively than a comparable patient whose lesions clear without sequelae. Hygiene plays little role in acne treatment, and a mild soap is almost always recommended. The agents effective in comedonal acne are listed below in the order in which they should be tried.
Tretinoin is very effective for comedonal acne or for treatment of the comedonal component of more severe acne, but its usefulness is limited by irritation. Start with 0.025% cream (not gel) and have the patient use it at first twice weekly at night, increasing frequency to nightly as tolerated. A few patients cannot use even this low-strength preparation more than three times weekly but even that may cause improvement. A lentil-sized amount is sufficient to cover the entire face. To avoid irritation, have the patient wait 20 minutes after washing to apply. Adapalene gel 0.1% and reformulated tretinoin (Renova, Retin A Micro, Avita) are other options for patients irritated by standard tretinoin preparations. Although the absorption of tretinoin is minimal, its use during pregnancy is contraindicated. Patients should be warned that their acne may flare in the first 4 weeks of treatment.
Benzoyl peroxide products are available in concentrations of 2.5%, 4%, 5%, 8%, and 10%, but 2.5% is as effective as 10% and less irritating. In general, water-based and not alcohol-based gels should be used to decrease irritation. Benzoyl peroxide in combination with several other topical agents, including adapalene and topical antibiotics (erythromycin, clindamycin phosphate), are available as a single formulation.
C. Papular or Cystic Inflammatory Acne
Brief treatment (3 weeks to 3 months) with topical or oral antibiotics is the mainstay for treatment of inflammatory acne that does not respond to topical therapy with retinoids or benzoyl peroxide. Topical clindamycin phosphate and erythromycin are used only for mild papular acne that can be controlled by topicals alone or for patients who refuse or cannot tolerate oral antibiotics. To decrease resistance, benzoyl peroxide should be used in combination with the topical antibiotic.
The first choice of topical antibiotics in terms of efficacy and relative lack of induction of resistant P acnes is the combination of erythromycin or clindamycin with benzoyl peroxide topical gel or wash. These may be used once or twice daily. The addition of tretinoin cream or gel at night may increase improvement, since it works via a different mechanism. Topical retinoids ideally are used after acne clearance is achieved as a long-term maintenance therapy.
Common oral antibiotics used for acne include doxycycline (100 mg twice daily), minocycline (50–100 mg once or twice daily), TMP-SMZ (one double-strength tablet twice daily), or a cephalosporin (cefadroxil or cephalexin 500 mg twice daily) may be used in combination with benzoyl peroxide to minimize development of antibiotic resistance. Once the patient’s skin is clear, instructions should be given for tapering the dose by 50% every 6–8 weeks—while treating with topicals—to arrive at the lowest systemic dose needed to maintain clearing. In general, discontinuing antibiotics immediately without adjunctive topical therapy results in prompt recurrence. Topical retinoids are excellent for long-term maintenance following antibiotics. Combination oral contraceptives or spironolactone (50–200 mg/day) may be added in women with treatment-resistant acne. Tetracycline, minocycline, and doxycycline are contraindicated in pregnancy, but certain oral erythromycins or cephalosporins may be used.
A vitamin A analog, isotretinoin is used for the treatment of severe acne that has not responded to conventional therapy. A dosage of 0.5–1 mg/kg/day for 20 weeks for a cumulative dose of at least 120 mg/kg is usually adequate for severe cystic acne. Patients should be offered isotretinoin therapy before they experience significant scarring if they are not promptly and adequately controlled by antibiotics. The medication is absolutely contraindicated during pregnancy because of its teratogenicity; two serum pregnancy tests should be obtained before starting the drug in women and every month thereafter. Sufficient medication for only 1 month can be dispensed. Two forms of effective contraception must be used; abstinence is an acceptable first option. Informed consent must be obtained before its use, and patients must be enrolled in a monitoring program (iPledge). In addition to its teratogenicity, isotretinoin has numerous serious side effects and should only be prescribed by clinicians (usually dermatologists) well aware of these issues. Side effects occur in most patients, usually related to dry skin and mucous membranes (dry lips, nosebleed, and dry eyes). If headache occurs, pseudotumor cerebri must be considered. Depression has been reported. Hypertriglyceridemia will develop in about 25% of patients. Mild transaminitis may develop in some patients. Fasting blood sugar may be elevated. Miscellaneous adverse reactions include decreased night vision, musculoskeletal symptoms, thinning of hair, exuberant granulation tissue in lesions, and bony hyperostoses (seen only with very high doses or with long duration of therapy). Moderate to severe myalgias rarely necessitate decreasing the dosage or stopping the drug. Inflammatory bowel disease has first appeared after acne treatment with both tetracyclines and isotretinoin at a rate of 1:1000 cases treated or less. Causality of this association has not been established. Young adults with severe acne who are potential candidates for isotretinoin should be asked about any bowel symptoms prior to starting isotretinoin. Consider ordering laboratory tests, including complete blood cell count (CBC), cholesterol levels, triglyceride levels, and liver function studies, in patients before treatment and after 4 weeks on therapy; monitoring through the entire treatment may not be high value.
Abnormal laboratory tests, especially elevated liver enzymes and triglyceride levels, return to normal quickly upon conclusion of therapy. The medication may induce long-term remissions in 40–60%, or acne may recur that is more easily controlled with conventional therapy. Occasionally, a second course is needed if acne does not respond or recurs.
B. Intralesional injection
Intralesional injection of dilute suspensions of triamcinolone acetonide (2.5 mg/mL, 0.05 mL per lesion) will often hasten the resolution of deeper papules and occasional cysts.
Cosmetic improvement may be achieved by excision and punch-grafting of deep scars and by physical or chemical abrasion of inactive acne lesions, particularly flat, superficial scars. Corrective surgery within 12 months after isotretinoin therapy may not be advisable.
Acne vulgaris eventually remits spontaneously, but when this will occur cannot be predicted. The condition may persist throughout adulthood and may lead to severe scarring if left untreated. Patients treated with antibiotics continue to improve for the first 3–6 months of therapy. Relapse during treatment may suggest the emergence of resistant P acnes. The disease is chronic and tends to flare intermittently in spite of treatment. Remissions following systemic treatment with isotretinoin may be lasting in up to 60% of cases. Relapses after isotretinoin usually occur within 3 years and require a second course in up to 20% of patients. Immediate relapse after isotretinoin discontinuation may suggest hyperandrogenism or other underlying hormonal disorders in a female patient.
et al. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012 Jul 11;7:CD004425.
et al. Recent advances in acne pathogenesis: implications for therapy. Am J Clin Dermatol. 2014 Dec;15(6):479–88.
et al; Global Alliance to Improve Outcomes in Acne. Antibiotic stewardship in dermatology: limiting antibiotic use in acne. Eur J Dermatol. 2014 May–Jun;24(3):330–4.
et al; Global Alliance to Improve Outcomes in Acne. Large-scale international study enhances understanding of an emerging acne population: adult females. J Eur Acad Dermatol Venereol. 2015 Jun;29(6):1096–106.
et al. Acne in the adult female patient: a practical approach. Int J Dermatol. 2012 Oct;51(10):1162–74.
et al. Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in acne vulgaris. J Am Acad Dermatol. 2014 Sep;71(3):450–9.
ESSENTIALS OF DIAGNOSIS
A chronic disorder affecting the face.
A neurovascular component (erythema and telangiectasis and a tendency to flush easily).
An acneiform component (papules and pustules) may also be present.
A glandular component accompanied by hyperplasia of the soft tissue of the nose (rhinophyma) (eFigure 6–71).
Rosacea is a common condition that presents in adulthood. The pathogenesis of this chronic disorder is not known. Topical corticosteroids applied to the face can induce rosacea-like conditions (eFigure 6–73).
This eruption resembling rosacea occurred following topical use of a steroid cream. (Used, with permission, from S Goldstein.)
Patients frequently report flushing or exacerbation of their rosacea due to heat, hot drinks, spicy food, sunlight, exercise, alcohol, emotions, or menopausal flushing. The cheeks, nose, and chin—at times the entire face—may be affected. No comedones are seen. In its mildest form, erythema and dilated vessels are seen on the cheeks. Inflammatory papules may be superimposed on this background and may evolve to pustules (Figure 6–21) (eFigure 6–74). Associated seborrhea may be found. The patient often complains of burning or stinging with episodes of flushing and extremely cosmetic-intolerant skin. Patients may have associated ophthalmic disease, including blepharitis and keratitis, which often requires topical or systemic antibiotic or immunosuppressive therapy.
Rosacea. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Acne rosacea. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Rosacea is distinguished from acne by the presence of the neurovascular component and the absence of comedones (eFigure 6–72). The rosy hue of rosacea and telangiectasis will pinpoint the diagnosis. Lupus is often misdiagnosed, but the presence of pustules excludes that diagnosis.
Educating patients to avoid the factors they know to produce exacerbations is important. Patients should wear a broad-spectrum sunscreen with UVA coverage; however, exquisite sensitivity to topical preparations may limit patient options. Zinc- or titanium-based sunscreens are tolerated best. Medical management is most effective for the inflammatory papules and pustules and the erythema that surrounds them. Rosacea is usually a lifelong condition, so maintenance therapy is required.
Avoidance of triggers (especially alcohol and spicy or hot foods) and drinking ice water may be effective in reducing facial erythema and flushing. Metronidazole (available as creams, gels, or lotions), 0.75% applied twice daily or 1% applied once daily, and ivermectin 1% cream applied once daily are effective topical treatments. Another effective treatment includes topical clindamycin (solution, gel, or lotion) 1% applied twice daily. Response is noted in 4–8 weeks. Sulfur-sodium sulfacetamide-containing topicals are helpful in patients only partially responsive to topical antibiotics. Topical retinoids can be carefully added for maintenance. Topical brimonidine tartrate gel 0.33% can temporarily reduce the flush/redness of rosacea patients.
Oral tetracyclines should be used when topical therapy is inadequate. Minocycline or doxycycline, 50–100 mg orally once or twice daily, is effective. Metronidazole or amoxicillin, 250–500 mg orally twice daily, or rifaximin, 400 mg orally three times daily (for 10 days), may be used in refractory cases. Side effects are few, although metronidazole may produce a disulfiram-like effect when the patient ingests alcohol, and it may cause neuropathy with long-term use. Long-term maintenance with subantimicrobial dosing of minocycline or doxycycline is recommended once the initial flare of rosacea has resolved. Isotretinoin may succeed where other measures fail. A dosage of 0.5 mg/kg/d orally for 12–28 weeks is recommended. See precautions above. Telangiectases are benefitted by laser therapy, and phymatous overgrowth of the nose can be treated by surgical reduction.
Rosacea tends to be a persistent process. With the regimens described above, it can usually be controlled adequately.
et al. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015 May;72(5):749–58.
et al. Rosacea: part II. Topical and systemic therapies in the treatment of rosacea. J Am Acad Dermatol. 2015 May;72(5):761–70.
et al. Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments. Br J Dermatol. 2015 Sep;173(3):651–62.
et al. Ocular rosacea: a dermatologic perspective. J Am Acad Dermatol. 2013 Dec;69(6 Suppl 1):S42–3.
et al. Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin. J Am Acad Dermatol. 2013 May;68(5):875–6.
FOLLICULITIS (INCLUDING SYCOSIS)
Folliculitis has multiple causes. It is frequently caused by staphylococcal infection and may be more common in the diabetic patient. When the lesion is deep-seated, chronic, and recalcitrant on the head and neck, it is called sycosis.
Gram-negative folliculitis, which may develop during antibiotic treatment of acne, may present as a flare of acne pustules or nodules. Klebsiella, Enterobacter, Escherichia coli, and Proteus have been isolated from these lesions.
Hot tub folliculitis (Pseudomonas folliculitis), caused by Pseudomonas aeruginosa, is characterized by pruritic or tender follicular, pustular lesions occurring within 1–4 days after bathing in a contaminated hot tub, whirlpool, or swimming pool (eFigure 6–75). Systemic flu-like symptoms may accompany cutaneous lesions. Rarely, systemic infections may result. Neutropenic patients should avoid these exposures.
Hot tub folliculitis presenting as tender follicular and pustular lesions 2 days after the patient was in a hot tub. (Used, with permission, from S Goldstein.)
Nonbacterial folliculitis may also be caused by friction and oils. Occlusion, perspiration, and rubbing, such as that resulting from tight jeans and other heavy fabrics on the upper legs can worsen this type of folliculitis.
Steroid acne may be seen during topical or systemic corticosteroid therapy and presents as eruptive monomorphous papules and papulopustules on the face and trunk. It responds to topical benzoyl peroxide.
Eosinophilic folliculitis is a sterile folliculitis that presents with urticarial papules with prominent eosinophilic infiltration. It is common in patients with AIDS. It may appear first with institution of highly active antiretroviral therapy (ART) and be mistaken for a drug eruption.
Pseudofolliculitis is caused by ingrowing hairs in the beard area. It occurs in men and women with tightly curled beard hair. In this entity, the papules and pustules are located at the side of and not in follicles. It may be treated by growing a beard, by using chemical depilatories, or by shaving with a foil-guard razor. Laser hair removal is dramatically beneficial in patients with pseudofolliculitis, requires limited maintenance, and can be done on patients of any skin color. Pseudofolliculitis is a true medical indication for such a procedure and should not be considered cosmetic.
Malassezia (Pityrosporum) folliculitis presents as 1–2-mm pruritic pink papulopustules on the upper trunk and arms. It is often pruritic and tends to develop during periods of excessive sweating.
The symptoms range from slight burning and tenderness to intense itching. The lesions consist of pustules of hair follicles (Figure 6–22) (eFigure 6–76).
Bacterial folliculitis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Folliculitis. A follicle is virtually completely destroyed and replaced by a neutrophilic abscess. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
It is important to differentiate bacterial from nonbacterial folliculitis. The history is important for pinpointing the causes of nonbacterial folliculitis, and a Gram stain and culture are indispensable. One must differentiate folliculitis from acne vulgaris (eFigure 6–70) or pustular miliaria (heat rash) (eFigure 6–77) and from infections of the skin, such as impetigo or fungal infections, especially Malassezia (Pityrosporum) folliculitis. Pseudomonas folliculitis is often suggested by the history of hot tub use. Eosinophilic folliculitis in AIDS often requires biopsy for diagnosis.
An example of miliaria crystalline denoted by vesicular eruption over the trunk of this patient. Miliaria rubra can simulate folliculitis. (Used, with permission, from I Frieden.)
Abscess formation is the major complication of bacterial folliculitis.
Correct any predisposing local causes, such as oils or friction. Be sure that the water in hot tubs and spas is treated properly. If staphylococcal folliculitis is persistent, treatment of nasal or perineal carriage with rifampin, 600 mg daily for 5 days, or with topical mupirocin ointment 2% twice daily for 5 days, may help. Prolonged oral clindamycin, 150–300 mg/day for 4–6 weeks, or oral TMP-SMZ given 1 week per month for 6 months can be effective in preventing recurrent staphylococcal folliculitis and furunculosis. Bleach baths (¼ to ½ cup per 20 liters of bathwater for 15 minutes 3–5 times weekly) may reduce cutaneous staphylococcal carriage and not contribute to antibiotic resistance. Control of blood glucose in diabetes may reduce the number of these infections.
Anhydrous ethyl alcohol containing 6.25% aluminum chloride (Xerac AC), applied three to seven times weekly to lesions and environs, may be helpful, especially for chronic frictional folliculitis of the buttocks. Topical antibiotics are generally ineffective if bacteria have invaded the hair follicle but may be prophylactic if used as an aftershave in patients with recurrent folliculitis after shaving.
Pseudomonas folliculitis will clear spontaneously in non-neutropenic patients if the lesions are superficial. It may be treated with ciprofloxacin, 500 mg twice daily for 5 days.
Systemic antibiotics are recommended for bacterial folliculitis due to other organisms. Extended periods of treatment (4–8 weeks or more) with antistaphylococcal antibiotics are required if infection has involved the scalp or densely hairy areas, such as the axilla, beard, or groin.
Gram-negative folliculitis in acne patients may be treated with isotretinoin in compliance with all precautions discussed above (see Acne Vulgaris).
Eosinophilic folliculitis may be treated initially by the combination of potent topical corticosteroids and oral antihistamines. In more severe cases, treatment is with one of the following: topical permethrin (application for 12 hours every other night for 6 weeks); itraconazole, 200–400 mg daily; UVB or PUVA phototherapy; or isotretinoin, 0.5 mg/kg/day for up to 5 months. A remission may be induced by some of these therapies, but long-term treatment may be required.
Malassezia (Pityrosporum) folliculitis is treated with topical sulfacetamide lotion twice a day, alone or in combination with itraconazole or fluconazole.
Bacterial folliculitis is occasionally stubborn and persistent, requiring prolonged or intermittent courses of antibiotics.
et al. Facial bacterial infections: folliculitis. Clin Dermatol. 2014 Nov–Dec;32(6):711–4.
et al. Malassezia infections: a medical conundrum. J Am Acad Dermatol. 2014 Jul;71(1):170–6.
et al. What is your diagnosis? Demodex folliculitis. Cutis. 2012 Aug;90(2):62, 65–6, 69.
ESSENTIALS OF DIAGNOSIS
Burning, itching, superficial aggregated small vesicles, papules, or pustules on covered areas of the skin, usually the trunk.
More common in hot, moist climates.
Rare forms associated with fever and even heat prostration.
Miliaria occurs most commonly on the trunk and intertriginous areas. A hot, moist environment is the most frequent cause. Occlusive clothing required for certain occupations may increase the risk. Bedridden febrile patients are susceptible. Plugging of the ostia of sweat ducts occurs, with ultimate rupture of the sweat duct, producing an irritating, stinging reaction. Increase in numbers of resident aerobes, notably cocci, plays a role. Medications that enhance sweat gland function (eg, clonidine, beta-blockers, opioids) may contribute.
The usual symptoms are burning and itching. The histologic depth of sweat gland obstruction determines the clinical presentation: miliaria crystallina in the superficial (subcorneal) epidermis, miliaria rubra in the deep epidermis, and miliaria profunda in the dermis. The lesions consist of small (1–3 mm) nonfollicular lesions. Subcorneal thin-walled, discrete clear fluid-filled vesicles are termed “miliaria crystallina.” When fluid is turbid and lesions present as vesicopustules or pustules, they are called miliaria pustulosa. Miliaria rubra (prickly heat) presents as pink papules. Miliaria profunda presents as nonfollicular skin-colored papules that develop after multiple bouts of miliaria rubra (eFigure 6–77). In a hospitalized patient, the reaction virtually always affects the back.
Miliaria is to be distinguished from drug eruption and folliculitis.
Use of an antibacterial preparation, such as chlorhexidine, prior to exposure to heat and humidity may help prevent the condition. Frequent turning or sitting of the hospitalized patient may reduce miliaria on the back.
The patient should keep cool and wear light clothing. Triamcinolone acetonide, 0.1% in Sarna lotion, or a mid-potency corticosteroid in a lotion or cream may be applied two to four times daily. Secondary infections (superficial pyoderma) are treated with appropriate antistaphylococcal antibiotics. Anticholinergic medications (eg, glycopyrrolate 1 mg orally twice a day) may be helpful in severe cases
Miliaria is usually a mild disorder, but severe forms (tropical anhidrosis and asthenia) result from interference with the heat-regulating mechanism.
et al. sQUIZ your knowledge! “Water-drop” lesions in a febrile patient. Miliaria crystalline (MC). Eur J Dermatol. 2012 Jan–Feb;22(1):160–1.
et al. In vivo imaging of miliaria profunda using high-definition optical coherence tomography: diagnosis, pathogenesis, and treatment. JAMA Dermatol. 2015 Mar 1;151(3):346–8.
ESSENTIALS OF DIAGNOSIS
Severe pruritus of vulva, anus, or body folds.
Superficial denuded, beefy-red areas with or without satellite vesicopustules.
Whitish curd-like concretions on the oral and vaginal mucous membranes.
Yeast and pseudohyphae on microscopic examination of scales or curd.
Mucocutaneous candidiasis is a superficial fungal infection that may involve almost any cutaneous or mucous surface of the body. It is particularly likely to occur in diabetics, during pregnancy, and in obese persons. Systemic antibiotics, oral corticosteroids, and oral contraceptive agents may be contributory. Oral and interdigital candidiasis may be the first sign of HIV infection (see Chapter 31). Denture use predisposes the elderly to infection. The Th-17 pathway is important in maintaining host defense against Candida infections, and mutations that interfere with normal Th-17 function predispose to Candida infection of the skin and mucous membranes.
Itching may be intense. Burning is reported, particularly around the vulva and anus. The lesions consist of superficially denuded, beefy-red areas in the depths of the body folds, such as in the groin and the intergluteal cleft, beneath the breasts, at the angles of the mouth, in the webspaces of digits, and in the umbilicus. The peripheries of these denuded lesions are superficially undermined, and there may be satellite vesicopustules. Whitish, curd-like concretions may be present on mucosal lesions (Figure 6–23). Paronychia may occur (Figure 6–24).
Oral mucosal candidiasis. (Used with permission from Sol Silverman, Jr, DDS, Public Health Image Library, CDC.)
Acute paronychia. (From EJ Mayeaux, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Clusters of budding yeast and pseudohyphae can be seen under high power (400×) when skin scales or curd-like lesions are mounted in 10% KOH (eFigure 6–40). Culture can confirm the diagnosis.
Intertrigo (eFigure 6–27), seborrheic dermatitis (eFigure 6–35), tinea cruris, “inverse psoriasis” (eFigure 6–46), and erythrasma involving the same areas may mimic mucocutaneous candidiasis (eFigure 6–47).
Systemic invasive candidiasis with candidemia may be seen with immunosuppression and in patients receiving broad-spectrum antibiotic and hypertonic glucose solutions, as in hyperalimentation. There may or may not be clinically evident mucocutaneous candidiasis.
Affected parts should be kept dry and exposed to air as much as possible. Water immersion should be minimized and gloves should be worn for those with infected nails or digital skin. If possible, discontinue systemic antibiotics. For treatment of systemic invasive candidiasis, see Chapter 36.
Apply clotrimazole solution 1% twice daily. Thymol 4% in ethanol applied once daily is an alternative.
Apply nystatin ointment or clotrimazole cream 1%, either with hydrocortisone cream 1%, twice daily. Gentian violet 0.5% solution is economical and highly effective in treating mucocutaneous candidiasis, but the purple discoloration may represent a cosmetic issue. Severe or widespread cutaneous disease responds to fluconazole, 100–200 mg daily, for 1 week.
3. Vulvar and anal mucous membranes
For vaginal candidiasis, single-dose fluconazole (150 mg orally) is effective. Intravaginal clotrimazole, miconazole, terconazole, or nystatin may also be used. Long-term suppressive therapy may be required for recurrent or “intractable” cases. Non-albicans candidal species may be identified by culture in some refractory cases and may respond to oral itraconazole, 200 mg twice daily for 2–4 weeks.
This is most frequent in uncircumcised men, and Candida usually plays a role. Topical nystatin ointment is the initial treatment if the lesions are mildly erythematous or superficially erosive. Soaking with dilute aluminum acetate for 15 minutes twice daily may quickly relieve burning or itching. Chronicity and relapses, especially after sexual contact, suggest reinfection from a sexual partner who should be treated. Severe purulent balanitis is usually due to bacteria. If it is so severe that phimosis occurs, oral antibiotics—some with activity against anaerobes—are required; if rapid improvement does not occur, urologic consultation is indicated.
Lancinating breast pain and nipple dermatitis in breast-feeding women may be a manifestation of Candida colonization/infection of the breast ducts. Topical nystatin cream and clotrimazole 0.1% cream are safe during lactation. Topical gentian violet 0.5% daily for 7 days is also useful. Oral fluconazole, 200 mg daily can be dramatically effective.
Cases of cutaneous candidiasis range from the easily cured to the intractable and prolonged.
et al. Clinical and microbiological diagnosis of oral candidiasis. J Clin Exp Dent. 2013 Dec 1;5(5):e279–86.
et al. Mycology—an update part 2: dermatomycoses: clinical picture and diagnostics. J Dtsch Dermatol Ges. 2014 Sep;12(9):749–77.
et al. Primary immunodeficiency update: Part II. Syndromes associated with mucocutaneous candidiasis and noninfectious cutaneous manifestations. J Am Acad Dermatol. 2015 Sep;73(3):367–81.
et al. Oral candidiasis: An overview. J Oral Maxillofac Pathol. 2014 Sep;18(Suppl 1):S81–5.
1. Urticaria & Angioedema
ESSENTIALS OF DIAGNOSIS
Eruptions of evanescent wheals or hives.
Itching is usually intense but may, on rare occasions, be absent.
Special forms of urticaria have special features (dermatographism, cholinergic urticaria, solar urticaria, or cold urticaria).
Most incidents are acute and self-limited over a period of 1–2 weeks.
Chronic urticaria (episodes lasting longer than 6 weeks) may have an autoimmune basis.
Urticaria can result from many different stimuli on an immunologic or nonimmunologic basis. The most common immunologic mechanism is mediated by IgE, as seen in the majority of patients with acute urticaria; another involves activation of the complement cascade. Some patients with chronic urticaria demonstrate autoantibodies directed against mast cell IgE receptors. ACE inhibitor and angiotensin receptor blocker therapy may be complicated by urticaria or angioedema. In general, extensive costly workups are not indicated in patients who have urticaria. A careful history and physical examination are more helpful.
Lesions are itchy, red swellings of a few millimeters to many centimeters (Figure 6–25). The morphology of the lesions may vary over a period of minutes to hours, resulting in geographic or bizarre patterns (eFigure 6–78) (eFigure 6–79). Individual lesions in true urticaria last less than 24 hours, and often only 2–4 hours. Angioedema is involvement of deeper subcutaneous tissue with swelling of the lips, eyelids, palms, soles, and genitalia. Angioedema is no more likely than urticaria to be associated with systemic complications, such as laryngeal edema or hypotension. In cholinergic urticaria, triggered by a rise in core body temperature (hot showers, exercise), wheals are 2–3 mm in diameter with a large surrounding red flare. Cold urticaria is acquired or inherited and triggered by exposure to cold and wind (see Chapter 37).
Urticaria. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Urticaria (hives). (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Wheal of cold urticaria precipitated by placing an ice cube on the patient's arm. Note the pattern created when ice water ran down the arm. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
The most common causes of acute urticaria are foods, infections, and medications. The cause of chronic urticaria is often not found. Laboratory studies are not likely to be helpful in the evaluation of acute or chronic urticaria. In patients with individual lesions that persist past 24 hours, skin biopsy may confirm neutrophilic urticaria or urticarial vasculitis. A functional ELISA test looking for antibodies against the high-affinity receptor for IgE (Fc-Epislon RI) can detect patients with an autoimmune basis for their chronic urticaria.
Papular urticaria resulting from insect bites persists for days. A central punctum can usually be seen. Streaked urticarial lesions may be seen in the 24–48 hours before blisters appear in acute allergic plant dermatitis, eg, poison ivy, oak, or sumac (eFigure 6–65). Urticarial responses to heat, sun, water, and pressure are quite rare. Urticarial vasculitis may be seen as part of serum sickness, associated with fever and arthralgia. In this setting, a low serum complement level may be associated with severe systemic disease.
In hereditary angioedema, there is generally a positive family history and gastrointestinal or respiratory symptoms. Urticaria is not part of the syndrome, and lesions are not pruritic.
A detailed search by history for a cause of acute urticaria should be undertaken, and treatment may then be tailored to include the provocative condition. The chief causes are medications—eg, aspirin, NSAIDs, morphine, and codeine; arthropod bites—eg, insect bites and bee stings (though the latter may cause anaphylaxis as well as angioedema); physical factors, such as heat, cold, sunlight, and pressure; and, presumably, neurogenic factors, as in cholinergic urticaria induced by exercise, excitement, hot showers, etc. Other causes may include penicillins and other medications; inhalants such as feathers and animal danders; ingestion of shellfish, tomatoes, or strawberries; infections, such as viral hepatitis (causing urticarial vasculitis); and in selected patients salicylates and tartrazine dyes.
The mainstay of treatment initially includes H1-antihistamines. Initial therapy is hydroxyzine, 10 mg twice daily to 25 mg three times daily, or as a single nightly dose of 50–75 mg to reduce daytime sedation. Cyproheptadine, 4 mg four times daily, may be especially useful for cold urticaria. “Nonsedating” or less sedating antihistamines are added if the generic sedating antihistamines are not effective. Options include fexofenadine, 180 mg once daily; or cetirizine or loratadine, 10 mg daily. Higher doses of these second-generation antihistamines may be required to suppress urticaria (up to four times the standard recommended dose) than are required for allergic rhinitis. These high doses are safe and can be used in refractory cases. Montelukast (10 mg daily) in combination with antihistamines appears to have a therapeutic benefit.
Doxepin (a tricyclic antidepressant with potent antihistaminic properties), 10–75 mg at bedtime, can be very effective in chronic urticaria. It has anticholinergic side effects.
H2-antihistamines in combination with H1-blockers may be helpful in patients with symptomatic dermatographism and to a lesser degree in chronic urticaria. UVB phototherapy can suppress some cases of chronic urticaria. If a skin biopsy of a lesion of chronic urticaria identifies neutrophils as a significant component of the inflammatory infiltrate, dapsone or colchicine (or both) may be useful.
A few patients with chronic urticaria may respond to elimination of salicylates and tartrazine (a coloring agent). Asymptomatic foci of infection—sinusitis, vaginal candidiasis, cholecystitis, and intestinal parasites—may rarely cause chronic urticaria. Although systemic corticosteroids in a dose of about 40 mg daily will usually suppress acute and chronic urticaria, the use of corticosteroids is rarely indicated and, once withdrawn, the urticaria virtually always returns. Instead of instituting systemic corticosteroids, consultation should be sought from a dermatologist or an allergist with experience in managing severe urticaria. Cyclosporine (3–5 mg/kg/day), mycophenolate mofetil, and other immunosuppressives may be effective in severe cases of chronic urticaria. Omalizumab is approved for the treatment of refractory chronic urticaria and should be considered when severe chronic urticaria fails to respond to high-dose antihistamines.
Local treatment is rarely rewarding.
Acute urticaria usually lasts only a few days to weeks. Half of patients whose urticaria persists for longer than 6 weeks will have it for years. Patients in whom angioedema develops with an ACE inhibitor may be switched to an angiotensin receptor blocker with caution (estimated cross-reaction about 10%).
et al. Treatment of refractory chronic urticaria: current and future therapeutic options. Am J Clin Dermatol. 2013 Dec;14(6):481–8.
et al. Chapter 21: Urticaria and angioedema. Allergy Asthma Proc. 2012 May–Jun;33(Suppl 1):S70–2.
et al. Efficacy and safety of omalizumab
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2. Erythema Multiforme/Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
ESSENTIALS OF DIAGNOSIS
Sudden onset of symmetric erythematous skin lesions with history of recurrence.
May be macular, papular, urticarial, bullous, or purpuric.
”Target” lesions with clear centers and concentric erythematous rings or “iris” lesions may be noted in erythema multiforme minor. Well-defined target lesions are rare in drug-associated Stevens-Johnson syndrome.
Erythema multiforme minor presents on the extensor surfaces, palms, soles, or mucous membranes. Stevens-Johnson syndrome favors the trunk.
Herpes simplex is the most common cause of erythema multiforme minor.
Medications are the most common cause of Stevens-Johnson syndrome in adults.
Erythema multiforme is an acute inflammatory skin disease that was traditionally divided clinically into minor and major types based on the clinical findings. Approximately 90% of cases of erythema multiforme minor follow outbreaks of herpes simplex, and so is preferably termed herpes-associated erythema multiforme. The term “erythema multiforme major” has been replaced by three terms: Stevens-Johnson syndrome (SJS), with less than 10% BSA detachment; toxic epidermal necrolysis (TEN) when there is greater than 30% BSA detachment; and SJS/TEN overlap for cases with between 10% and 30% BSA detachment. The abbreviation SJS/TEN is often used to refer to these three variants of what is considered one syndrome. All these clinical scenarios are characterized by toxicity and involvement of two or more mucosal surfaces (often oral and conjunctival). They are most often caused by medications, especially sulfonamides, NSAIDs, allopurinol, and anticonvulsants. In certain races, polymorphisms of antigen-presenting major histocompatibility (MHC) loci increase the risk for the development of SJS/TEN. Mycoplasma pneumoniae may trigger a mucocutaneous reaction with skin and oral lesions closely resembling Stevens-Johnson syndrome in up to 50% of children/young adults in some series. The exposure to medications associated with SJS/TEN may be systemic or topical (eg, eyedrops).
A classic target lesion, found most commonly in herpes-associated erythema multiforme, consists of three concentric zones of color change, most often found acrally on the hands and feet (eFigure 6–80). Medication-associated bullous eruptions in the SJS/TEN spectrum present with raised purpuric target-like lesions, with only two zones of color change and a central blister, or nondescript reddish or purpuric macules favoring the trunk and proximal upper extremities (Figure 6–26) (eFigure 6–81) (eFigure 6–82). Pain on eating, swallowing, and urination can occur if the appropriate mucosae are involved (eFigure 6–83).
Stevens-Johnson syndrome. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Erythema multiforme with classic target lesions. Note the three zones of color change. (Used, with permission, from I Frieden.)
Erythema multiforme: target or iris lesion. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Erythema multiforme: gyrate erythema. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Patient with erythema multiforme major demonstrating oral lesions on lips, buccal mucosa, and tongue. (Used, with permission, from S Goldstein.)
Blood tests are not useful for diagnosis. Skin biopsy is diagnostic. Direct immunofluorescence studies are negative.
Urticaria and drug eruptions are the chief entities that must be differentiated from erythema multiforme minor (eFigure 6–78). In true urticaria, lesions are not purpuric or bullous, last less than 24 hours, and respond to antihistamines. The differential diagnosis of SJS/TEN includes autoimmune bullous diseases (eg, pemphigus, pemphigoid, and linear IgA bullous dermatosis) (eFigure 6–84) (eFigure 6–85), acute systemic lupus erythematosus, vasculitis, and Sweet syndrome. The presence of a blistering eruption requires biopsy and consultation for appropriate diagnosis and treatment.
Pemphigus vulgaris with flaccid bullae demonstrating easy separation of the epidermis (Nikolsky sign). (Used, with permission, from R Odom.)
Bullous pemphigoid: tense bullae. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
The tracheobronchial mucosa, conjunctiva, and urethral mucosa may be involved in severe cases with resultant scarring. Ophthalmologic consultation is required if ocular involvement is present because vision loss is the major consequence of SJS/TEN.
Toxic epidermal necrolysis is best treated in an acute care environment, which may include an ICU or a burn unit. Patients should be admitted if mucosal involvement interferes with hydration and nutrition or extensive blistering develops. Open lesions should be managed like second-degree burns. Immediate discontinuation of the inciting medication (before blistering occurs) is a significant predictor of outcome. Delay in establishing the diagnosis and inadvertently continuing the offending medication results in higher morbidity and mortality.
The most important aspect of treatment is to stop the offending medication and to move patients with greater than 25–30% BSA involvement to an appropriate acute care environment. Nutritional and fluid support and high vigilance for infection are the most important aspects of care. Reviews of systemic treatments for SJS and TEN have been conflicting. Some data support the use of high-dose corticosteroids. If corticosteroids are to be tried, they should be used early, before blistering occurs, and in moderate to high doses (prednisone, 1–2 mg/kg/day) and stopped within days if there is no dramatic response. Intravenous immunoglobulin (IVIG) (1 g/kg/day for 4 days) has become standard of care at some centers for toxic epidermal necrolysis cases. IVIG used early in the course and at a total dose of at least 2 g/kg may result in decreased mortality, although not all studies support this finding. Cyclosporine (3–5 mg/kg/day for 7 days) may also be effective. Tumor necrosis factor inhibitors are used at some centers as well. Oral and topical corticosteroids are useful in the oral variant of erythema multiforme. Oral acyclovir prophylaxis of herpes simplex infections may be effective in preventing recurrent herpes-associated erythema multiforme minor.
Topical therapy is not very effective in this disease.
Erythema multiforme minor usually lasts 2–6 weeks and may recur. SJS/TEN may be serious with a mortality of about 30% in cases with greater than 30% BSA involvement. SCORTEN (a severity of illness scale) predicts mortality in SJS/TEN.
et al. Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with meta-regression of observational studies. Int J Dermatol. 2015 Jan;54(1):108–15.
et al. Mycoplasma pneumoniae
-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. J Am Acad Dermatol. 2015 Feb;72(2):239–45.
et al. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol. 2012 Aug;167(2):424–32.
et al. Retrospective review of Stevens-Johnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine
. J Am Acad Dermatol. 2014 Nov;71(5):941–7.
M. Stevens-Johnson syndrome and toxic epidermal necrolysis: clinical patterns, diagnostic considerations, etiology, and therapeutic management. Semin Cutan Med Surg. 2014 Mar;33(1):10–6.
et al. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014 Aug;71(2):278–83.
et al. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol. 2012 Aug;51(8):889–902.
et al. Toxic epidermal necrolysis: performance of SCORTEN and the score-based comparison of the efficacy of corticosteroid therapy and intravenous immunoglobulin combined therapy in China. J Burn Care Res. 2012 Nov;33(6):e295–308.
Erythema migrans is a unique cutaneous eruption that characterizes the localized or generalized early stage of Lyme disease (caused by Borrelia burgdorferi) (Figure 6–27) (See also Chapter 34). Three to 32 days (median: 7 days) after a tick bite, there is gradual expansion of redness around the papule representing the bite site. The advancing border is usually slightly raised, warm, red to bluish-red, and free of any scale. Centrally, the site of the bite may clear, leaving only a rim of peripheral erythema, or it may become indurated, vesicular, or necrotic. The annular erythema usually grows to a median diameter of 15 cm (range: 3–68 cm, but virtually always greater than 5 cm). It is accompanied by a burning sensation in half of patients; rarely, it is pruritic or painful. Multiple secondary annular lesions similar in appearance to the primary lesion but without indurated centers and generally of smaller size will develop in 20% of patients but may be even more common in European patients. In the southeastern United States, similar lesions are seen in patients who are not as ill and who tend to have classic central clearing of their lesions. These patients have negative Lyme serology tests. This condition has been called Southern tick-associated rash illness (STARI). This illness is transmitted by the lone star tick Amblyomma americanum and some cases have been shown to be caused by Borrelia lonestari, for which the white tail deer is the animal reservoir. Systemic symptoms are uncommon in STARI and the skin lesions respond to the same antibiotic agents used for Lyme disease, suggesting that a spirochete (probably as yet unidentified Borrelia species) is causative in all these cases.
Erythema migrans due to Borrelia burgdorferi (Lyme disease). (Used, with permission, from James Gathany, Public Health Image Library, CDC.)
Without treatment, erythema migrans and the secondary lesions fade in a median of 28 days, though some may persist for months. Ten percent of untreated patients experience recurrences over the ensuing months. Treatment with systemic antibiotics (see Table 34–4) is necessary to prevent systemic involvement. However, only 60–70% of those with systemic involvement have experienced erythema migrans.
et al. Lyme disease: Part I. Advances and perspectives. J Am Acad Dermatol. 2011 Apr;64(4):619–36.
et al. Lyme disease: Part II. Management and prevention. J Am Acad Dermatol. 2011 Apr;64(4):639–53.
et al. The many faces of solitary and multiple erythema migrans. Acta Derm Venereol. 2013 Nov;93(6):693–700.
et al. Differentiation of reinfection from relapse in recurrent Lyme disease. N Engl J Med. 2012 Nov 15;367(20):1883–90.
ESSENTIALS OF DIAGNOSIS
Edematous, raised, circumscribed, hot, erythematous area, with or without vesicles or bullae.
Central face or lower extremity frequently involved.
Pain, chills, fever, and systemic toxicity may be striking.
Erysipelas is a superficial form of cellulitis that is caused by beta-hemolytic streptococci.
The symptoms are pain, malaise, chills, and moderate fever. A bright red spot appears and then spreads to form a tense, sharply demarcated, glistening, smooth, hot plaque (eFigure 6–86). The margin characteristically makes noticeable advances in days or even hours. The lesion is edematous with a raised edge and may pit slightly with the finger. Vesicles or bullae occasionally develop on the surface. The lesion does not usually become pustular or gangrenous and heals without scar formation. The disease may complicate any break in the skin that provides a portal of entry for the organism. On the face, erysipelas begins near a fissure at the angle of the nose. On the lower extremity, tinea pedis with interdigital fissuring is a common portal of entry.
Characteristic features of erysipelas present in this patient include an advancing, edematous, well-circumscribed erythema on the face. (Used, with permission, from S Goldstein.)
Leukocytosis is almost invariably present; blood cultures may be positive.
Erysipeloid is a benign bacillary infection producing cellulitis of the skin of the fingers or the backs of the hands in fishermen and meat handlers.
Unless erysipelas is promptly treated, death may result from extension of the process and systemic toxicity, particularly in the elderly.
Intravenous antibiotics effective against group A beta-hemolytic streptococci and staphylococci should be considered, but outpatient treatment with oral antibiotics has demonstrated equal efficacy. Oral regimens include a 7-day course with penicillin VK (250 mg), dicloxacillin (250 mg), or a first-generation cephalosporin (250 mg) orally four times a day. Alternatives in penicillin-allergic patients are clindamycin (250 mg twice daily orally for 7–14 days) or erythromycin (250 mg four times daily orally for 7–14 days), the latter only if the infection is known to be due to streptococci.
With appropriate treatment, rapid improvement is expected. The presence of lymphedema carries the greatest risk of recurrence.
ESSENTIALS OF DIAGNOSIS
Edematous, expanding, erythematous, warm plaque with or without vesicles or bullae.
Lower leg is frequently involved.
Pain, chills, and fever are commonly present.
Septicemia may develop.
Cellulitis, a diffuse spreading infection of the dermis and subcutaneous tissue, is usually on the lower leg (Figure 6–28) and most commonly due to gram-positive cocci, especially group A beta-hemolytic streptococci and S aureus. Rarely, gram-negative rods or even fungi can produce a similar picture. In otherwise healthy persons, the most common portal of entry for lower leg cellulitis is toe web intertrigo with fissuring, usually a complication of interdigital tinea pedis. Other diseases that predispose to cellulitis are prior episodes of cellulitis, chronic edema, venous insufficiency with secondary edema, lymphatic obstruction, saphenectomy, and other perturbations of the skin barrier. Bacterial cellulitis is almost never bilateral.
Cellulitis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
Cellulitis begins as a tender small patch. Swelling, erythema, and pain are often present. The lesion expands over hours, so that from onset to presentation is usually 6 to 36 hours. As the lesion grows, the patient becomes more ill with progressive chills, fever, and malaise. Lymphangitis and lymphadenopathy are often present. If septicemia develops, hypotension may develop, followed by shock.
Leukocytosis or at least a neutrophilia (left shift) is present from early in the course. Blood cultures may be positive. If a central ulceration, pustule, or abscess is present, culture may be of value. Aspiration of the advancing edge has a low yield (20%) and is usually not performed. In immunosuppressed patients, or if an unusual organism is suspected and there is no loculated site to culture, a full thickness skin biopsy taken before antibiotics are given can be useful. Either two specimens or one divided in half should be sent for routine histologic evaluation and for culture. Skin biopsy is particularly important in the immunocompromised patient in whom cellulitis may be due to an uncommon organism. If a primary source for the infection is identified (wound, leg ulcer, toe web intertrigo), cultures from these sites isolate the causative pathogen in half of cases and can be used to guide antibiotic therapy.
Two potentially life-threatening entities that can mimic cellulitis (ie, present with a painful, red, swollen lower extremity) include deep venous thrombosis and necrotizing fasciitis. The diagnosis of necrotizing fasciitis should be suspected in a patient who has a very toxic appearance, bullae, crepitus or anesthesia of the involved skin, overlying skin necrosis, and laboratory evidence of rhabdomyolysis (elevated creatine kinase [CK]) or disseminated intravascular coagulation. While these findings may be present with severe cellulitis and bacteremia, it is essential to rule out necrotizing fasciitis because rapid surgical debridement is essential. Other skin lesions that may resemble cellulitis include sclerosing panniculitis, an acute, exquisitely tender red plaque on the medial lower legs above the malleolus in patients with venous stasis or varicosities, and acute severe contact dermatitis on a limb, which produces erythema, vesiculation, and edema, as seen in cellulitis, but with itching instead of pain. Bilateral lower leg bacterial cellulitis is exceedingly rare, and other diagnoses, especially severe stasis dermatitis (see Figure 12–1), should be considered in this setting. Severe lower extremity stasis dermatitis usually develops over days to weeks rather than the hours of cellulitis. It is also not as tender to palpation as cellulitis. Cryptococcal cellulitis in the organ transplant recipient is often bilateral.
Intravenous or parenteral antibiotics may be required for the first 2–5 days, with adequate coverage for Streptococcus and Staphylococcus. Methicillin-susceptible S aureus (MSSA) can be treated with nafcillin, cefazolin, clindamycin, dicloxacillin, cephalexin, doxycycline, or TMP-SMZ. If MRSA is suspected or proven, treatment options include vancomycin, linezolid, clindamycin, daptomycin, doxycycline, or TMP-SMZ. In mild cases or following the initial parenteral therapy, dicloxacillin or cephalexin, 250–500 mg four times daily for 5–10 days, is usually adequate. In patients in whom intravenous treatment is not instituted, the first dose of oral antibiotic can be doubled to achieve high blood levels rapidly. In patients with recurrent lower leg cellulitis (3–4 episodes per year), oral penicillin 250 mg twice daily or erythromycin can delay the appearance of the next episode. Prior episodes of cellulitis, lymphedema, chronic venous insufficiency, peripheral vascular disease, and deep venous thrombosis are associated with an increased risk of recurrent cellulitis.
Severe local symptoms and signs.
Systemic inflammatory response syndrome (SIRS) criteria are met.
Elevated white blood cell count with marked left shift.
Failure to respond to oral antibiotics.
et al. Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review and meta-analysis. J Infect. 2014 Jul;69(1):26–34.
et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):147–59.
et al. Inpatient dermatology consultation aids diagnosis of cellulitis among hospitalized patients: a multi-institutional analysis. J Am Acad Dermatol. 2015 Jul;73(1):70–5.
et al. Cellulitis Recurrence Score: a tool for predicting recurrence of lower limb cellulitis. J Am Acad Dermatol. 2015 Jan;72(1):140–5.
ESSENTIALS OF DIAGNOSIS
Relapsing crops of bullae, often fragile and leading to erosions.
Often preceded by mucous membrane bullae, erosions, and ulcerations.
Superficial detachment of the skin after pressure or trauma variably present (Nikolsky sign).
Acantholysis on biopsy.
Immunofluorescence studies and serum ELISA for pathogenic antibodies are confirmatory.
Pemphigus is an uncommon intraepidermal blistering disease occurring on skin and mucous membranes. It is caused by autoantibodies to adhesion molecules expressed in the skin and mucous membranes. The cause is unknown, and in the preantibiotic, presteroid era, the condition was usually fatal within 5 years. The bullae appear spontaneously and are tender and painful when they rupture. Drug-induced pemphigus from penicillamine, captopril, and others has been reported. There are several forms of pemphigus: pemphigus vulgaris and its variant, pemphigus vegetans; and the more superficially blistering pemphigus foliaceus and its variant, pemphigus erythematosus. All forms may occur at any age, but most present in middle age. The vulgaris form begins in the mouth in over 50% of cases. The foliaceus form is especially apt to be associated with other autoimmune diseases, or it may be drug-induced. Paraneoplastic pemphigus, a unique form of the disorder, is associated with numerous types of benign and malignant neoplasms but most frequently non-Hodgkin lymphoma.
Pemphigus is characterized by an insidious onset of flaccid bullae, crusts, and erosions in crops or waves (Figure 6–29) (eFigure 6–84). In pemphigus vulgaris, lesions often appear first on the oral mucous membranes. These rapidly become erosive. The scalp is another site of early involvement. Rubbing a cotton swab or finger laterally on the surface of uninvolved skin may cause easy separation of the epidermis (Nikolsky sign).
Pemphigus. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)
The diagnosis is made by light microscopy and by direct and indirect immunofluorescence (IIF) microscopy. Autoantibodies to intercellular adhesion molecules (desmoglien 3 and 1) can be detected with ELISA assays and have replaced the use of IIF in some centers.
Blistering diseases include erythema multiforme (eFigure 6–80), SJS/TEN, drug eruptions, bullous impetigo, contact dermatitis (eFigure 6–70), dermatitis herpetiformis (eFigure 6–66), and bullous pemphigoid (eFigure 6–85), but flaccid blisters are not typical of these diseases, and acantholysis is not seen on biopsy. All of these diseases have clinical characteristics and different immunofluorescence test results that distinguish them from pemphigus.
Paraneoplastic pemphigus is clinically, histologically, and immunologically distinct from other forms of the disease. Oral erosions and erythematous plaques resembling erythema multiforme are seen. Survival rates are low because of the underlying malignancy.
Secondary infection commonly occurs; this is a major cause of morbidity and mortality. Disturbances of fluid, electrolyte, and nutritional intake can occur as a result of painful oral ulcers.
When the disease is severe, hospitalize the patient at bed rest and provide antibiotics and intravenous feedings as indicated. Anesthetic troches used before eating ease painful oral lesions.
Pemphigus requires systemic therapy as early in its course as possible. However, the main morbidity in this disease is due to the side effects of such therapy. Initial therapy is with systemic corticosteroids: prednisone, 60–80 mg daily. In all but the mildest cases, a steroid-sparing agent is added from the beginning, since the course of the disease is long and the steroid-sparing agents take several weeks to exert their activity. Azathioprine (100–200 mg daily) or mycophenolate mofetil (1–1.5 g twice daily) are used most frequently. Rituximab treatment (1 g intravenously on days 1 and 15), especially early in the course, appears to be associated with therapeutic induction of a complete remission and is increasingly being used as first-line therapy. Repeated courses are efficacious and well tolerated in patients who do not achieve complete remission or relapse. Monthly IVIG at 2 g/kg intravenously over 3–4 days frequently is beneficial. In refractory cases, cyclophosphamide, pulse intravenous corticosteroids, and plasmapheresis can be used. Increased risk of thromboembolism is associated with IVIG therapy at these doses.
In patients with limited disease, skin and mucous membrane lesions should be treated with topical corticosteroids. Complicating infection requires appropriate systemic and local antibiotic therapy.
The course tends to be chronic in most patients, though about one-third appear to experience remission. Infection is the most frequent cause of death, usually from S aureus septicemia.
et al. First-line treatment of pemphigus vulgaris with a combination of rituximab
and high-potency topical corticosteroids. JAMA Dermatol. 2015 Feb;151(2):200–3.
K. Importance of serological tests in diagnosis of autoimmune blistering diseases. J Dermatol. 2015 Jan;42(1):3–10.
et al. Diagnosis and clinical features of pemphigus vulgaris. Immunol Allergy Clin North Am. 2012 May;32(2):233–43.
Many other autoimmune skin disorders are characterized by formation of bullae, or blisters. These include bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, and pemphigoid gestationis.
Bullous pemphigoid is a relatively benign pruritic disease characterized by tense blisters in flexural areas, usually remitting in 5 or 6 years, with a course characterized by exacerbations and remissions (eFigure 6–85). Most affected persons are over the age of 60 (often in their 70s or 80s), and men are affected twice as frequently as women. The appearance of blisters may be preceded by pruritic urticarial or edematous lesions for months. Oral lesions are present in about one-third of affected persons. The disease may occur in various forms, including localized, vesicular, vegetating, erythematous, erythrodermic, and nodular.
The diagnosis is made by biopsy and direct immunofluorescence examination. Light microscopy shows a subepidermal blister. With direct immunofluorescence, IgG and C3 are found at the dermal-epidermal junction. When ELISA testing for bullous pemphigoid antibodies BP 180 or BP 230 is performed, positivity of either will be found in 97% of patients. If the patient has mild disease, ultrapotent corticosteroids may be adequate. Prednisone at a dosage of 0.75 mg/kg daily is often used to achieve rapid control of more widespread disease. Tetracycline (500 mg three times daily), alone or combined with nicotinamide—not nicotinic acid or niacin—(up to 1.5 g/day), may control the disease in patients who cannot use corticosteroids or may allow decreasing or eliminating corticosteroids after control is achieved. Dapsone is particularly effective in mucous membrane pemphigoid. If these medications are not effective, methotrexate, 5–25 mg weekly, azathioprine, 50 mg one to three times daily, or mycophenolate mofetil (1–1.5 g twice daily) may be used as steroid-sparing agents. Intravenous immunoglobulin, rituximab, and omalizumab have been used with success in refractory cases.
et al. First-line combination therapy with rituximab
and corticosteroids provides a high complete remission rate in moderate-to-severe bullous pemphigoid. Br J Dermatol. 2015 Jul;173(1):302–4.
et al. High-dose intravenous immunoglobulin in the treatment of adult patients with bullous pemphigoid. Eur J Dermatol. 2012 May–Jun;22(3):363–9.
K. Importance of serological tests in diagnosis of autoimmune blistering diseases. J Dermatol. 2015 Jan;42(1):3–10.
ESSENTIALS OF DIAGNOSIS
Verrucous papules anywhere on the skin or mucous membranes, usually no larger than 1 cm in diameter.
Prolonged incubation period (average 2–18 months).
Spontaneous “cures” are frequent in common warts (50% at 2 years).
“Recurrences” (new lesions) are frequent.
Warts (common, plantar, and genital) are caused by human papillomaviruses (HPVs). Typing of HPV lesions is not a part of standard medical evaluation except in the case of anogenital dysplasia.
There are usually no symptoms. Tenderness on pressure occurs with plantar warts; itching occurs with anogenital warts (Figure 6–30) (eFigure 6–87). Flat warts are most evident under oblique illumination. Periungual warts may be dry, fissured, and hyperkeratotic and may resemble hangnails. Plantar warts resemble plantar corns or calluses.
Condylomata acuminata, or genital warts, of the anal region due to human papillomavirus. (Public Health Image Library, CDC.)
Perianal condylomata acuminata. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Some warty-looking lesions are actually hypertrophic actinic keratoses or squamous cell carcinomas (eFigure 6–88). Some genital warty lesions may be due to secondary syphilis (condylomata lata). The lesions of molluscum contagiosum are pearly with a central dell (eFigure 6–89). In AIDS, wart-like lesions may be caused by varicella zoster virus.
Squamous cell carcinoma. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Waxy umbilicated papules of molluscum contagiosum are spread by wet skin-to-skin contact. (Used, with permission, from K Zipperstein.)
Administration of a vaccine against certain anogenital HPV types (including 6, 11, 16, 18) can prevent infection with these wart types and reduce anogenital, oropharyngeal, and cervical cancer. It is recommended for teenagers and young adults (see Chapters 1 and 18).
Treatment is aimed at inducing “wart-free” intervals for as long as possible without scarring, since no treatment can guarantee a remission or prevent recurrences. In immunocompromised patients, the goal is even more modest, ie, to control the size and number of lesions present.
For common warts of the hands, patients are usually offered liquid nitrogen or keratolytic agents. The former may work in fewer treatments but requires office visits and is painful.
Liquid nitrogen is applied to achieve a thaw time of 30–45 seconds. Two freeze-thaw cycles are given every 2–4 weeks for several visits. Scarring will occur if it is used incorrectly. Liquid nitrogen may cause permanent depigmentation in pigmented individuals. Cryotherapy is first-line physician-applied surgical treatment for genital warts (condyloma acuminata).
2. Keratolytic agents and occlusion
Salicylic acid products may be used against common warts or plantar warts. They are applied, then occluded. Plantar warts may be treated by applying a 40% salicylic acid plaster after paring. The plaster may be left on for 5–6 days, then removed, the lesion pared down, and another plaster applied. Although it may take weeks or months to eradicate the wart, the method is safe and effective with almost no side effects. Chronic occlusion alone with water-impermeable tape (duct tape, adhesive tape) is less effective than cryotherapy.
For genital warts, the purified active component of the podophyllum resin, podofilox, is applied by the patient twice daily 3 consecutive days a week for cycles of 4–6 weeks. It is less irritating and more effective than “physician-applied” podophyllum resin. After a single 4-week cycle, 45% of patients were wart-free; but of these, 60% relapsed at 6 weeks. Thus, multiple cycles of treatment are often necessary. Patients unable to obtain the take-home podofilox may be treated in the clinician’s office by painting each wart carefully (protecting normal skin) every 2–3 weeks with 25% podophyllum resin (podophyllin) in compound tincture of benzoin. Podophyllin is ineffective for common warts and plantar warts and should not be used in pregnant women (pregnancy category X).
A 5% cream of this local interferon inducer has moderate activity in clearing external genital warts. Treatment is once daily on 3 alternate days per week. Response may be slow, with patients who eventually cleared having responses at 8 weeks (44%) or 12 weeks (69%). There is a marked difference between the sexes with respect to response, with 77% of women and 40% of men having complete clearing of their lesions. Once cleared, about 13% have recurrences in the short term.
Although imiquimod is considerably more expensive than podophyllotoxin, its high rate of response in women and its safety (pregnancy category B) make it the “patient-administered” treatment of choice for external genital warts in women. In men, the more rapid response, lower cost, and similar efficacy make podophyllotoxin the initial treatment of choice, with imiquimod used for recurrences or refractory cases. Imiquimod has no demonstrated efficacy for—and should not be used to treat—plantar or common warts.
Plantar warts may be removed by blunt dissection. For genital warts, snip biopsy (scissors) removal followed by light electrocautery is more effective than cryotherapy, especially for patients with pedunculated or large lesions.
The CO2 laser can be effective for treating recurrent warts, periungual warts, plantar warts, and condylomata acuminata. It leaves open wounds that must fill in with granulation tissue over 4–6 weeks and is best reserved for warts resistant to all other modalities. Lasers with emissions of 585, 595, or 532 nm may also be used every 3–4 weeks to gradually ablate common or plantar warts. This is no more effective than cryotherapy in controlled trials. For genital warts, it has not been shown that laser therapy is more effective than electrosurgical removal. Photodynamic therapy can be considered in refractory widespread flat and genital warts.
Bleomycin diluted to 1 unit/mL may be injected into common and plantar warts. It has been shown to have a high cure rate. It should be used with caution on digital warts because of the potential complications of Raynaud phenomenon, nail loss, and terminal digital necrosis. 5-Fluorouracil 5% cream applied once or twice daily, usually with occlusion, may be applied to warts with the similar efficacy to other treatment methods.
Squaric acid dibutylester may be applied in a concentration of 0.2–2% directly to the warts from once weekly to five times weekly to induce a mild contact dermatitis. Between 60% and 80% of warts clear over 10–20 weeks. Injection of Candida antigen starting at 1:50 dilution and repeated every 3–4 weeks may be similarly effective in stimulating immunologic regression of common and plantar warts.
Soaking warts in hot (42.2°C) water for 10–30 minutes daily for 6 weeks has resulted in involution in some cases.
There is a striking tendency to develop new lesions. Warts may disappear spontaneously or may be unresponsive to treatment.
et al. Use of Candida
antigen injections for the treatment of verruca vulgaris: a two-year mayo clinic experience. J Dermatolog Treat. 2015 Nov 11:1–4. [Epub ahead of print]
et al. Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer. J Infect. 2013 Mar;66(3):207–17.
et al. Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus
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et al. Annual Report to the Nation on the Status of Cancer, 1975–2009, featuring the burden and trends in human papillomavirus
(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013 Feb 6;105(3):175–201.
et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012 Sep 12;9:CD001781.
et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus
vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014 Aug 29;63(RR-05):1–30.
et al. Systematic review of the incidence and prevalence of genital warts. BMC Infect Dis. 2013 Jan 25;13:39.
CALLOSITIES & CORNS OF FEET OR TOES
Callosities and corns are caused by pressure and friction due to faulty weight-bearing, orthopedic deformities, improperly fitting shoes, or neuropathies.
Tenderness on pressure and "after-pain" are the only symptoms. The hyperkeratotic well-localized overgrowths always occur at pressure points. Dermatoglyphics (fingerprint lines) are preserved over the surface (not so in warts). When the surface is shaved with a 15 blade, a glassy core is found (which differentiates them from plantar warts, which have multiple capillary bleeding points or black dots when pared).
Treatment consists of correcting mechanical abnormalities that cause friction and pressure. Callosities may be removed by careful paring of the callus after a warm water soak or with keratolytic agents as found in various brands of corn pads.
Plantar hyperkeratosis of the heels can be treated successfully by using 20% urea (Ureacin 20) or 12% lactic acid (Amlactin) or combinations nightly and a pumice stone after soaking in water.
Callosities on diabetic feet, especially in the setting of hyposensate neuropathy, can be a major problem and the value of early podiatric management to prevent complications is very high.
et al. Beneficial effects of foot care nursing for people with diabetes mellitus: an uncontrolled before and after intervention study. J Adv Nurs. 2011 Sep;67(9):1952–62.
Molluscum contagiosum, caused by a poxvirus, presents as single or multiple dome-shaped, waxy papules 2–5 mm in diameter that are umbilicated (Figure 6–31) (eFigure 6–89). Lesions at first are firm, solid, and flesh-colored but upon reaching maturity become soft, whitish, or pearly gray and may suppurate. The principal sites of involvement are the face, lower abdomen, and genitals.
Molluscum contagiosum lesion on the back. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
The lesions are autoinoculable and spread by wet skin-to-skin contact. In sexually active individuals, they may be confined to the penis, pubis, and inner thighs and are considered a sexually transmitted infection.
Molluscum contagiosum is common in patients with AIDS, usually with a helper T-cell count less than 100/mcL. Extensive lesions tend to develop over the face and neck as well as in the genital area.
The diagnosis is easily established in most instances because of the distinctive central umbilication of the dome-shaped lesion. It has been estimated that time to remission is 13 months. The best treatment is by curettage or applications of liquid nitrogen as for warts—but more briefly. When lesions are frozen, the central umbilication often becomes more apparent. Light electrosurgery with a fine needle is also effective. Ten percent potassium hydroxide solution applied twice daily until lesions clear is emerging as a viable treatment option. They are difficult to eradicate in patients with AIDS unless immunity improves. However, in AIDS, with highly effective antiretroviral treatment, molluscum do not need to be treated because they usually spontaneously clear.
et al. Comparison of 10% potassium hydroxide solution versus cryotherapy in the treatment of molluscum contagiosum: an open randomized clinical trial. J Dermatolog Treat. 2014 Jun;25(3):249–50.
et al. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study. Lancet Infect Dis. 2015 Feb;15(2):190–5.
ESSENTIALS OF DIAGNOSIS
Pearly papule, erythematous patch greater than 6 mm, or nonhealing ulcer in sun-exposed areas (face, trunk, lower legs).
History of bleeding.
Fair-skinned person with a history of sun exposure (often intense, intermittent).
Basal cell carcinomas are the most common form of cancer. They occur on sun-exposed skin in otherwise normal, fair-skinned individuals; ultraviolet light is the cause. The most common presentation is a papule or nodule that may have a central scab or erosion (Figure 6–32) (eFigure 6–90). Occasionally the nodules have stippled pigment (pigmented basal cell carcinoma). Intradermal nevi without pigment on the face of older white individuals may resemble basal cell carcinomas. Basal cell carcinomas grow slowly, attaining a size of 1–2 cm or more in diameter, usually only after years of growth. There is a waxy, “pearly” appearance, with telangiectatic vessels easily visible (eFigure 6–91) (eFigure 6–92). It is the pearly or translucent quality of these lesions that is most diagnostic, a feature best appreciated if the skin is stretched (eFigure 6–93). On the back and chest, basal cell carcinomas appear as reddish, somewhat shiny, scaly patches. Basal cell carcinomas are more common and more likely to recur in immunosuppressed patients, including those with non-Hodgkin lymphoma and those who have undergone solid organ or allogeneic hematopoietic stem cell transplantation.
Nodular basal cell carcinoma of the nose. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Basal cell carcinoma. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Basal cell carcinoma on the forehead with irregular distribution of the telangiectases and lack of typical doughnut shape. (Used, with permission, from Richard P. Usatine, MD in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Basal cell carcinoma. Note the somewhat translucent hue and surface telangiectasia. (Reproduced, with permission, from Orkin M, Maibach HI, Dahl MV [editors]. Dermatology. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
Basal cell carcinoma located on the inferomedial eyelid. It is the pearly or translucent quality of these lesions that is most diagnostic. (Used, with permission, from S Goldstein.)
Lesions suspected to be basal cell carcinomas should be biopsied, by shave or punch biopsy (eFigure 6–94) (eFigure 6–95). Therapy is then aimed at eradication with minimal cosmetic deformity, often by excision and suturing with recurrence rates of 5% or less. The technique of three cycles of curettage and electrodesiccation depends on the skill of the operator and is not recommended for head and neck lesions. After 4–6 weeks of healing, it leaves a broad, hypopigmented, at times hypertrophic scar. Radiotherapy is effective and sometimes appropriate for older individuals (over age 65), but recurrent tumors after radiation therapy are more difficult to treat and may be more aggressive. Radiation therapy is the most expensive method to treat basal cell carcinoma and should only be used if other treatment options are not appropriate. Mohs surgery—removal of the tumor followed by immediate frozen section histopathologic examination of margins with subsequent reexcision of tumor-positive areas and final closure of the defect—gives the highest cure rates (98%) and results in least tissue loss. It is an appropriate therapy for tumors of the eyelids, nasolabial folds, canthi, external ear, and temple; for recurrent lesions; or where tissue sparing is needed for cosmesis. Vismodegib is reserved for the treatment of advanced or metastatic basal cell carcinoma or in patients with extensive tumor burden (eg, basal cell nevus syndrome). Imiquimod may be appropriate for select patients with superficial basal cell carcinomas, but the treated area must be observed for evidence of complete cure. Since a second lesion will develop in up to half of patients with a basal cell carcinoma, patients with basal cell carcinomas must be monitored at least yearly to detect new or recurrent lesions.
Stretching of the skin prior to biopsy. (Reproduced, with permission, from Chesnutt MS et al. Office & Bedside Procedures. Originally published by Appleton & Lange. Copyright © 1992 by The McGraw-Hill Companies, Inc.)
Typical ellipsoid defect after removal of the biopsy specimen. (Reproduced, with permission, from Chesnutt MS et al. Office & Bedside Procedures. Originally published by Appleton & Lange. Copyright © 1992 by The McGraw-Hill Companies, Inc.)
Ad Hoc Task Force; Connolly
et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012 Oct;67(4):531–50.
et al. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol. 2015 Jun;16(6):729–36.
et al. Increased incidence and recurrence rates of nonmelanoma skin cancer in patients with non-Hodgkin lymphoma: a Rochester Epidemiology Project population-based study in Minnesota. J Am Acad Dermatol. 2015 Feb;72(2):302–