29: Rash

In clinical practice, rashes are diagnosed through pattern recognition probably more than any other complaint. This is an effective way of making a diagnosis when the diagnosis is obvious or when the observer is very experienced. The risk with pattern recognition is that diagnostic hypotheses are heavily influenced by recent experience, rare diagnoses tend not to be recognized, and physicians often reach premature closure on an incorrect diagnosis.

The differential diagnosis of a rash should be based on the morphology of the lesion. To correctly categorize a lesion’s morphology, the physician must first identify the primary lesion, the typical element of the eruption. This process can be complicated. Identifying the primary lesion may be difficult as it is often affected by secondary changes such as excoriation, erosion, crusting, or coalescence. The differential diagnosis of 1 lesion can also be extensive. Once the morphology of the primary lesion is identified, the next step in making the diagnosis is often to observe the distribution of lesions. Some eruptions will have characteristic distributions. What follows are some important definitions, followed by a differential diagnosis of some of the most common primary lesions.

1. Macule: lesion without elevation or depression, < 1 cm

2. Patch: lesion without elevation or depression, > 1 cm

3. Papule: any solid, elevated “bump” < 1 cm

4. Plaque: raised plateau-like lesion of variable size, often a confluence of papules

5. Nodule: solid lesion with palpable elevation, 1–5 cm

6. Tumor: solid growth, > 5 cm

7. Cyst: encapsulated lesion, filled with soft material

8. Vesicle: elevated, fluid-filled blister, < 1 cm

9. Bulla: elevated, fluid-filled blister, > 1 cm

10. Pustule: elevated, pus-filled blister, any size

11. Wheal: inflamed papule or plaque formed by transient and superficial local edema

12. Comedone: a plug of keratinous material and skin oils retained in a follicle; open is black, closed is white

Papulosquamous eruptions present with papules and plaques associated with superficial scaling. Folliculopapular eruptions begin as papules arising in a perifollicular distribution. Dermal reaction patterns result from infiltrative and inflammatory processes involving the dermal and subcutaneous tissues. Petechia and purpura occur when there is leakage of blood products into surrounding tissues from inflamed or damaged blood vessels. Blistering disorders present with vesicles and bullae. Figure 29-1 presents an algorithm of a possible approach to patients with rashes and skin lesions.

1. Papulosquamous eruptions (papules and plaques)

   1. Eczematous dermatitis

      1. Atopic dermatitis

      2. Allergic contact dermatitis

      3. Irritant contact dermatitis

   2. Pityriasis rosea

   3. Tinea infections

   4. Psoriasis

   5. Seborrheic dermatitis

2. Folliculopapular eruptions (perifollicular papules)

   1. Acne vulgaris

   2. Rosacea

   3. Folliculitis

   4. Perioral dermatitis

3. Dermal reaction patterns

   1. Urticaria

   2. Sarcoidosis

   3. Granuloma annulare

   4. Erythema nodosum

4. Purpura and petechiae

   1. Palpable purpura

      1. Leukocytoclastic vasculitis

         • (1) Henoch-Schönlein purpura

         • (2) Allergic vasculitis

      2. Infectious

         • (1) Bacteremia

         • (2) Rocky Mountain spotted fever

         • (3) Meningococcemia

   2. Nonpalpable purpura

      1. Thrombocytopenia

      2. Medication-related

      3. Benign pigmented purpura

      4. Bacteremia

      5. Disseminated intravascular coagulation

      6. Actinic/senile purpura

      7. Corticosteroid-associated

      8. Amyloidosis

5. Blistering disorders (vesicles, pustules, and bullae)

   1. Autoimmune

      1. Bullous pemphigoid

      2. Pemphigus vulgaris

      3. Epidermolysis bullosa acquisita

   2. Infectious

      1. Varicella zoster

      2. Herpes simplex

      3. Impetigo

      4. Staphylococcal scalded skin

   3. Hypersensitivity syndromes

      1. Stevens-Johnson syndrome

      2. Toxic epidermal necrolysis

The pivotal clues in this case are the morphology of the lesion and its distribution. This patient has a folliculopapular eruption that predominantly affects the face, chest, and upper back. Primary lesions of inflammatory papules, pustules, and comedones place acne at the top of the differential. The history is typical for acne: a chronic course with intermittent flares.

Other folliculopapular conditions must be considered. The lack of background erythema and telangiectasias makes a diagnosis of rosacea less likely. Perioral dermatitis typically presents as monomorphic small papules and is closely associated with the use of topical corticosteroids and cosmetics. The mixture of lesion type, with comedones as well as papules and nodules, and the more diffuse distribution makes acne more likely than perioral dermatitis. An infectious folliculitis is possible, but the course of the disease makes this extremely unlikely (Table 29-1).

Leading Hypothesis: Acne Vulgaris

Textbook Presentation

Typically, acne vulgaris presents in adolescence with chronic, waxing and waning lesions. A variety of lesions are present, including inflammatory papules, pustules, comedones, and nodulocysts over the face, chest, and back.

Disease Highlights

1. Description of lesion: inflammatory papules, pustules, comedones, and nodulocysts over the face, chest, and back (see Figure 29-2).

2. Acne is a highly prevalent condition, most common during mid-to-late adolescence.

3. Acne may persist beyond adolescence, especially in women.

4. Acne is caused by the obstruction of sebaceous follicles on the face and trunk. Three factors are involved in the development of the lesions:

   1. Increased sebum is produced (androgen dependent) and accumulates in follicles.

   2. Desquamation of epithelial cells and keratin into sebum-rich follicles causes obstruction.

   3. Inflammation develops secondary to proliferation of the anaerobe Propionibacterium acnes.

5. Although the 3 factors discussed above are responsible for the overwhelming majority of acne, it is important to keep in mind other factors that may be contribute to the disease.

   1. Hyperandrogen states (eg, polycystic ovary syndrome [PCOS] or androgenic progestins in contraceptives).

   2. Exposure to topical comedogens (cocoa butter, mineral oil, lanolin, fatty acids).

   3. Numerous factors that lead to follicular obstruction (eg, habits or clothing that cause skin trauma or obstruct pores, and hot humid environments or heavy sweating leading to keratin over-hydration).

   4. Medications known to trigger or exacerbate acne (eg, corticosteroids, isoniazid, lithium, androgens).

Evidence-Based Diagnosis

1. The diagnosis is typically clinical.

2. Work-up for hyperandrogenism is appropriate when there are signs of polycystic ovary disease, virilization, or an atypical presentation (such as later in life).

Treatment

1. Establish that there are none of the acne precipitants discussed above.

2. Review general skin care techniques for acne-prone skin.

   1. Vigorous scrubbing can aggravate acne by promoting development of inflammatory lesions.

   2. Abrasive cleaners and mechanical devices also aggravate acne by promoting inflammation.

   3. Use of a mild cleanser with lukewarm water and one’s hands is best.

   4. Use of moisturizers should be minimized and all cosmetics and lotions should be oil-free.

   5. Minimize contact of facial skin with hair gels and other styling products (pomade acne).

3. Medical therapy is aimed at the 3 factors involved in acne development.

   1. Decreasing sebum production

      1. No topical therapies are effective

      2. Estrogen

         • (1) Most effective at doses of > 50 mcg of ethinyl estradiol

         • (2) Common oral contraceptive pills containing ≤ 35 mcg ethinyl estradiol are still helpful.

      3. Antiandrogens (spironolactone)

      4. Isotretinoin (see later discussion)

   2. Alteration of epithelial turnover and cohesiveness

      1. Topical retinoids: tretinoin, tazarotene

      2. Adapalene: a naphthoic acid with retinoid activity

   3. P acnes proliferation and accompanying inflammation

      1. Topical antibiotics

         • (1) Erythromycin

         • (2) Clindamycin

         • (3) Metronidazole

         • (4) Benzoyl peroxide

      2. Systemic antibiotics

         • (1) Tetracycline class

         • (2) Erythromycin

         • (3) Clindamycin

4. Guidelines for the use of these medications are as follows:

   1. Predominantly comedonal acne: retinoid or adapalene

   2. Mild inflammatory acne: topical antibiotic and benzoyl peroxide with or without retinoid or adapalene

   3. Moderate to severe but noncystic inflammatory acne: systemic antibiotic in combination with a topical retinoid

   4. Nodular cystic acne: isotretinoin

      1. Because of potential adverse effects with isotretinoin, it should only be prescribed by clinicians experienced in its use.

      2. Isotretinoin has the potential to cause hypertriglyceridemia and depression.

      3. Isotretinoin is a potent teratogen and effective contraception must be assured.

5. Additional considerations

   1. Oral contraceptives are useful in women with a strong hormonal component.

   2. Spironolactone can be useful in adult women with recalcitrant acne.

A clinical diagnosis of acne is most likely. Although PCOS might by considered based on the older age of the patient and the distribution of lesions along the jaw line, the patient lacks the oligomenorrhea that, along with evidence of hyperandrogenism, is necessary for making the diagnosis.

A clinical diagnosis of acne is made, and discussion about the most appropriate therapy begins.

Alternative Diagnosis: Rosacea

Textbook Presentation

Commonly presents in adults with a facial rash. There is gradual development of telangiectasias and persistent centrofacial erythema occasionally with inflammatory red papules and papulopustules. Comedones are absent. There is often a history of easy flushing. The rash may worsen with sun exposure, ingestion of spicy food and hot liquids, emotional stress, and exercise.

Disease Highlights

1. Description of lesion: centrofacial persistent facial erythema, telangiectasias, and, occasionally, inflammatory papules and papulopustules (Figure 29-3).

2. Rosacea is most common in fair-skinned individuals of northern European descent but can be seen in people with darker skin as well.

3. Women are more commonly affected than men.

4. However, complicated disease with sebaceous gland hyperplasia and rhinophyma (sebaceous overgrowth causing deformity of the nose) develops more often in men.

5. Rosacea typically begins later than acne and reaches a peak in middle age. That said the 2 can overlap.

6. Sun exposure is thought to be a trigger and sun-damaged skin is frequently seen in patients with rosacea.

Evidence-Based Diagnosis

1. Diagnosis is by clinical presentation.

2. Histopathology, which is rarely necessary, varies according to the stage and variant of the disease and is often nonspecific.

Treatment

1. Sun protection

2. Avoidance of triggers of flushing

   1. Sun exposure

   2. Ingestion of spicy foods and hot liquids

   3. Emotional stressors

   4. Physical exertion: encourage frequent cool-downs

3. Topical agents: metronidazole decreases erythema and prevents papules and papulopustules.

4. Systemic agents: oral antibiotics of the tetracycline class control severe eruptions of inflammatory lesions.

5. Laser treatment

   1. Used to ablate telangiectasias and improve background erythema.

   2. May be helpful to reduce rhinophyma.

Several general etiologic categories need to be considered when presented with a patient with new-onset blisters or vesicles. Blisters can be a symptom of infection, autoimmune disease, or a reaction to an external stimulus. Infectious causes include varicella zoster virus (VZV), presenting either as chickenpox or herpes zoster (shingles), and bullous impetigo. Both are possible in this patient. The prodromal pain suggests VZV. Bullous impetigo can cause blisters in a young, healthy person, but these blisters often begin in intertriginous areas. Bullous impetigo is most common in children. Grouped blisters suggest VZV or herpes simplex virus (HSV), whereas other blistering diseases may demonstrate large distinct blisters or erosions.

Bullous arthropod bites can affect patients of any age. A history of exposure should be elicited. The numerous, small, clustered lesions in this case make arthropod bites a less likely diagnosis. Bullous pemphigoid and other autoimmune blistering disorders are rare but possible. Stevens-Johnson syndrome is unlikely given the subacute onset but is certainly a “must not miss” diagnosis (Table 29-2).

Leading Hypothesis: Varicella Zoster Virus (Herpes Zoster/Shingles)

Textbook Presentation

This condition usually presents as a rash over a single, unilateral dermatome. The lesions begin as closely grouped vesicles on an erythematous base. Over 2–3 days, the lesions become pustular and then crust over after 7–10 days. Pain and paresthesias along the involved dermatome often precede the rash by a few days.

Disease Highlights

1. Description of the lesion: small, tightly grouped vesicles on an erythematous base occurring in one dermatome (see Figure 29-4). Very early in the presentation, the lesions are large papules that then become vesicular, then pustular, and ultimately crusted.

2. Characteristics of the lesion

   1. The rash tends to occur in the region where the rash of primary VZV infection (chickenpox) was most severe.

      1. The most common dermatomes are trigeminal and T3–L2.

      2. It is not uncommon to have a few vesicles in contiguous dermatomes.

   2. New lesions may appear for several days, occasionally for up to 7 days.

3. Shingles is caused by reactivation of VZV in a dorsal root ganglion.

4. Complications

   1. Herpes zoster ophthalmicus

      1. Can occur when there is involvement of the first division of the trigeminal nerve.

      2. The tip of the nose is in this division so vesicles in this area should raise the possibility of herpes zoster ophthalmicus.

      3. Herpes zoster ophthalmicus carries high risk of corneal damage.

   2. Ramsay Hunt syndrome

      1. Reactivation of VZV within the geniculate ganglion

      2. Causes a Bell palsy (facial paralysis) and ear pain

      3. Vesicles can often be seen in the ear canal.

      4. Vestibular and hearing disturbances (vertigo and hearing loss or tinnitus) are frequently reported.

5. Disseminated varicella zoster may occur, most often in immunocompromised patients.

6. Shingles in the elderly

   1. Shingles can be associated with significant morbidity in elderly patients.

   2. The rash is more severe and generally lasts longer in the elderly.

   3. Postherpetic neuralgia, a potentially debilitating, long-term pain syndrome, is also most common in the elderly.

Evidence-Based Diagnosis

1. The diagnosis of shingles is usually made clinically without additional tests.

2. Viral polymerase chain reaction (PCR) done of the vesicle fluid is useful if the diagnosis is in doubt.

3. The bedside Tzanck smear of material scraped from a fresh vesicle can be supportive evidence but cannot distinguish between VZV and HSV.

Treatment

1. In the immunocompetent, the eruption is self-limited; supportive care with pain relievers may be all that is necessary.

2. Patients with any involvement of the eye should be evaluated by an ophthalmologist.

3. Antiviral agents (acyclovir, famciclovir, valacyclovir)

   1. When the rash is diagnosed within the first 72 hours, systemic antiviral medications are useful.

   2. They decrease the duration and severity of the disease.

   3. They prevent dissemination.

   4. Early treatment with antiviral agents may also prevent the development of postherpetic neuralgia.

      The use of antiviral drugs is not beneficial if the rash of herpes zoster has been present for more than 72 hours.

4. Symptomatic care: soaks and topical antipruritics might be useful.

5. Corticosteroids

   1. Corticosteroids have been used in conjunction with antiviral agents to reduce the duration of the rash and the acute pain syndrome.

   2. A recent meta-analysis showed that corticosteroids are probably ineffective in the treatment of shingles.

6. Infection control

   1. The vesicle fluid is infectious to individuals who have not had chickenpox or been vaccinated.

   2. Infection risk can, therefore, be reduced by preventing direct contact with the vesicle fluid.

7. Postherpetic neuralgia

   1. Most commonly complicates disease in the elderly

   2. Potentially severe neuropathic pain syndrome

   3. Can be treated with tricyclic antidepressants, gabapentin, or opioids

   4. Intrathecal methylprednisolone and lidocaine are effective for refractory disease.

8. Prevention

   1. The shingles vaccine is effective prevention.

   2. The original trial of this vaccine was conducted in a population over 60 years of age and demonstrated a 48.5% reduction in episodes of zoster (NNT = 63) and a 45% reduction in cases of postherpetic neuralgia (NNT = 434).

   3. The vaccine is recommended for patients over the age of 60.

      1. Patients should receive the vaccine regardless of whether there is a history of chickenpox.

      2. The vaccine should also probably be given 3–4 years after an episode of shingles.

   4. Because this is a live-virus vaccine, it is contraindicated in patients who are immunosuppressed, pregnant, or planning pregnancy.

Given the patient’s prodromal symptoms and classic dermatomal distribution, VZV is the leading diagnosis. Because the rash was though to be somewhat atypical, a fresh vesicle was unroofed with a scalpel tip and the vesicle fluid was sent for PCR testing.

The diagnosis of varicella zoster is often clinical. The distribution and clinical appearance of lesions, as well as the associated prodromal symptoms, can make the diagnosis obvious. Impetigo, bullous arthropod bites, and autoimmune blistering diseases will typically demonstrate larger distinct blisters or erosions. Stevens-Johnson syndrome and other drug reactions must always be considered when medications are in use. This patient was taking amoxicillin. The clinical appearance of the lesions, their localized distribution, and the overall time course of the symptoms is not consistent with this eruption, so VZV must still lead the list.

Alternative Diagnosis: Bullous Impetigo

Textbook Presentation

Most commonly seen in children, bullous impetigo presents as flaccid, transparent bullae in the intertriginous areas. The blisters rupture easily and leave a rim of scale and a shallow moist erosion.

Disease Highlights

1. Description of the lesion: flaccid bullae on normal skin (Figure 29-5)

2. Location of the lesion

   1. Develops on grossly intact skin as a result of local toxin production.

   2. This is in contrast to nonbullous impetigo, shown in Figure 29-6, resulting from Staphylococcus or Streptococcus infection, which tends to affect previously traumatized skin.

   3. Lesions most commonly develop on moist, intertriginous skin.

3. Superficial skin infection that most commonly affects infants and young children

4. The causative agent is Staphylococcus aureus.

5. The blistering is caused by the production of exfoliatin or epidermolytic toxins.

Evidence-Based Diagnosis

1. Diagnosis is by clinical presentation.

2. Culture of blister fluid or the moist edge of a crusted plaque may be diagnostic.

Treatment

1. Oral antibiotics active against S aureus should be prescribed for bullous impetigo. The possibility of methicillin-resistant S aureus (MRSA) must be considered.

2. Localized, nonbullous impetigo may be adequately treated with topical antibiotics (effective against gram-positive cocci) such as:

   1. Bacitracin

   2. Polymyxin

   3. Mupirocin

3. Recurrent infections may indicate staphylococcal carriage. Eradication measures including daily washing with chlorhexidine gluconate, intranasal mupirocin ointment, and oral rifampin and doxycycline have been modestly successful.

4. Family members and close contacts may also be colonized and warrant investigation and treatment when appropriate. Environmental sources such as shared towels, athletic equipment and such should be considered.

Alternative Diagnosis: Bullous Arthropod Bites

Textbook Presentation

This condition commonly presents as a cluster of tense blisters on exposed skin. The blisters tend to be large (≥ 1 cm) and surrounding skin is normal.

Disease Highlights

1. Description of the lesion: large, often tense blisters on normal skin (Figure 29-7).

2. Character and location of the lesion

   1. The lesions tend to develop in exposed areas of the skin, such as the extremities.

   2. The patient will otherwise appear well.

   3. The lesions are typically extraordinarily pruritic.

   4. Although the blisters arise from otherwise normal skin, surrounding inflammatory changes from rubbing and scratching are often present.

3. Arthropod bite reactions are dermal hypersensitivity reactions to antigens in the saliva of insects.

4. Because bedbugs (as well as fleas) are a common culprit, this diagnosis has recently become more common.

Evidence-Based Diagnosis

1. Diagnosis is made by clinical presentation.

2. Histopathology, though rarely necessary, can be supportive, demonstrating edema, a subepidermal blister, and a dermal inflammatory infiltrate with numerous eosinophils.

Treatment

1. Avoidance of future bites with use of protective clothing and insect repellants.

2. Attention to eradicating the source of the biting insects, such as on pets, nests, etc.

3. Supportive local care to prevent secondary infection and relieve pruritus.

Alternative Diagnosis: Bullous Pemphigoid

Textbook Presentation

Bullous pemphigoid is usually seen in elderly patients with the sudden onset of 1–2 cm tense blisters and bright red, urticarial plaques. Lesions often begin on the lower extremities and progress upward.

Disease Highlights

1. Description of the lesion: tense bullae arising on skin that may be normal, erythematous, or urticarial (Figure 29-8).

2. Bullous pemphigoid is an autoimmune disease primarily affecting the elderly.

3. Autoantibodies are targeted against components of the epidermal basement membrane zone, thus triggering separation and blistering.

4. The lesions heal without scarring.

5. Most cases occur sporadically without obvious precipitating factors.

6. Character and location of the lesion

   1. Predilection of blisters for the extremities

   2. Lesions range from asymptomatic to intensely pruritic.

   3. Mucosal surfaces are rarely involved.

7. Antibodies to several elements of the basements membrane zone have been isolated. These distinct antibodies cause other blistering syndromes, such as pemphigus vulgaris and epidermolysis bullosa acquisita.

Evidence-Based Diagnosis

1. Histopathology provides supportive information, demonstrating a subepidermal blister plane and accumulation of eosinophils.

2. Immunopathology confirms the diagnosis by demonstrating linear deposits of IgG and C3 at the dermal–epidermal junction.

3. In 70–80% of patients, circulating IgG that recognizes the identified antigens of the basement membrane zone can be found.

Treatment

1. Topical, potent corticosteroids can be effective.

2. Extensive disease can be treated with systemic corticosteroids.

3. Steroid-sparing immunosuppressives are used to limit the toxicities of systemic corticosteroids in chronic disease.

4. Alternative antiinflammatory regimens such as tetracycline and nicotinamide may be effective.

5. Remission is usually obtained within a few weeks; however, some degree of long-term therapy may be necessary.

6. Refractory cases may respond to plasmapheresis or intravenous gammaglobulin.

Alternative Diagnosis: Stevens-Johnson Syndrome

Textbook Presentation

Stevens-Johnson syndrome typically presents in a patient with fever, malaise, headache, and myalgias who is taking a potentially causative medication. After about 1 week of symptoms, a macular rash develops on the chest and face. These lesions subsequently blister and then rapidly erode. The skin is usually excruciatingly tender.

Disease Highlights

1. Description of the lesion: flaccid bullae and vesicles that develop centrally within preexisting target lesion. The bullae rapidly erode, leaving red and raw skin (Figure 29-9).

2. Stevens-Johnson syndrome and toxic epidermal necrolysis are hypersensitivity reaction patterns involving the skin.

   1. These 2 conditions are often considered to be on a spectrum of severity. Stevens-Johnson syndrome involves less body surface area, whereas toxic epidermal necrolysis leads to considerable areas of full-thickness skin sloughing.

   2. Although the precise cause has not been found, drugs are involved in most cases.

3. More than 200 drugs have been implicated as causes of Stevens-Johnson syndrome and toxic epidermal necrolysis.

4. A well-done case-control trial identified the most likely culprits. These are listed in Table 29-3 with their associated ORs.

5. Disease course

   1. Prodromal symptoms, characterized by fever, malaise, headache, myalgias, as well as GI and respiratory complaints, occur over 1–2 weeks.

   2. The rash occurs initially on the face and central trunk as pink to red macules and papules.

   3. The rash may spread and evolve rapidly, with individual lesions becoming targetoid with dusky centers and ultimately coalescing into larger plaques.

   4. Flaccid bullae and vesicles may develop centrally within targets as the skin necroses.

   5. Blisters form and rapidly erode, leaving red and raw skin that becomes coated by a gray-white pseudomembrane.

   6. Mucous membranes

      1. Lesions on mucous membranes may accompany or precede the skin rash.

      2. The mucosal surfaces may be tender and burning.

      3. The lips are often swollen, cracked, bleeding, and crusted.

   7. The skin is extremely tender.

6. A hallmark of Stevens-Johnson syndrome and toxic epidermal necrolysis is the presence of exquisite skin tenderness.

Evidence-Based Diagnosis

1. Histopathology supports the clinical impression.

2. Pathology demonstrates epidermal necrosis with minimal evidence of epidermal and dermal inflammation.

Treatment

1. If an offending drug is present, it must be discontinued.

2. Some studies support the use of intravenous immunoglobulin in the early stages of the disease to abort progression.

3. Use of systemic corticosteroids is controversial. Studies have not proven that the benefit outweighs risk of immunosuppression.

4. Supportive care in a burn unit is recommended.

The appearance of the eruption suggests that this condition is papulosquamous in morphology (ie, it is composed primarily of papules and plaques with scale). Common causes of papulosquamous eruptions are psoriasis, pityriasis rosea, fungal infections, and nummular dermatitis.

The patient’s age, acute onset of the rash, and the pattern of small papules and plaques are pivotal points suggesting either guttate psoriasis or pityriasis rosea. In addition, the finding of pharyngeal injection suggests that there may be an infectious component (as is common with guttate psoriasis). The configuration of the lesions and the scale can be very helpful in narrowing the differential diagnosis. This patient’s scale is confluent over the surface of the lesions, consistent with guttate psoriasis. Tinea infections typically have scale at the border of the lesions (leading edge with advancing scale) and pityriasis rosea has scale at the center of the lesion (trailing scale). Nummular dermatitis is usually found on the extremities and is associated with significant pruritus, making it an unlikely diagnosis in this case. Secondary syphilis needs to be considered as a “must not miss” diagnosis. Syphilis can present with plaques, but they often involve the palms and soles and lack an adherent scale (Table 29-4).

Leading Hypothesis: Guttate Psoriasis

Textbook Presentation

Guttate psoriasis generally presents with small, round, and slightly oval lesions on the back and trunk. The lesions often have somewhat silvery, adherent scales.

Disease Highlights

1. Description of lesion: small (0.5–1.5 cm), round or slightly oval lesions with characteristic overlying silvery scales (see Figure 29-10).

2. Character of the lesion

   1. Lesions tend to occur over the upper trunk and proximal extremities.

   2. Face, ears, and scalp may also be involved.

   3. The lesions may localize to sites of minor skin trauma, such as scrapes (Koebner phenomenon).

   4. Eruption generally persists for 3–4 months and then remits spontaneously.

3. Most commonly seen in young adults, frequently preceded by a streptococcal throat infection.

4. Affected patients are at increased risk for development of psoriasis vulgaris in the next 3–5 years.

5. There is an increased incidence of psoriasis in families.

Evidence-Based Diagnosis

1. The diagnosis is often made based on the clinical presentation.

2. The presence of streptococcal pharyngitis would be a supportive finding.

3. A skin biopsy of an established lesion may demonstrate classic histologic findings of psoriasis vulgaris.

Treatment

1. Guttate psoriasis is typically a self-limited eruption, although clearance can take weeks to months.

2. Remission can be hastened with the use of UV light treatments.

3. Antibiotics with antiinflammatory properties, such as erythromycin and tetracycline, can be additionally helpful for flares.

   1. There is an infectious trigger in many cases.

   2. Appropriate antibiotic treatment of any potentially causative infection should be administered.

4. Topical corticosteroids can be effective on individual lesions.

5. Systemic corticosteroids should be avoided in psoriasis because withdrawal may trigger flares.

6. Topical calcipotriene, a vitamin D derivative, is also effective.

Based on the lesions’ morphology, family history, and recent pharyngitis, guttate psoriasis was considered the likely diagnosis. A throat culture was sent. A skin biopsy was considered but not performed.

Alternative Diagnosis: Pityriasis Rosea

Textbook Presentation

Pityriasis rosea commonly presents as a “herald patch” and then multiple small, oval, scaly plaques develop over the trunk. The rash is mildly pruritic.

Disease Highlights

1. Description of lesion: oval or round plaque with central (trailing) scale (Figure 29-11).

2. Character of the lesion

   1. The primary eruption appears as a single oval or round, pink to brownish plaque with a collarette of scale around the inner margin of the lesion (the herald patch). This herald patch most often occurs on the trunk and is often misdiagnosed as tinea corporis.

   2. One to 2 weeks after the appearance of the herald patch, the secondary eruption emerges as generalized smaller but similar oval scaly plaques distributed along skin tension lines in a “fir tree” pattern.

   3. Variable degrees of pruritus

   4. Spontaneous resolution occurs over 8–12 weeks, often with subsequent postinflammatory hypopigmentation or hyperpigmentation.

3. A history of a mild prodrome of malaise, nausea, headache, and low-grade fever may be present.

4. Pityriasis rosea is a common worldwide disease without genetic or racial predilection, occurring sporadically throughout the year.

5. A viral cause is postulated; evidence suggests but does not confirm a role for human herpesvirus 7.

Evidence-Based Diagnosis

1. The diagnosis is clinical, based on morphology and distribution of the skin lesions.

2. Skin biopsy demonstrates many nonspecific findings of a subacute dermatitis but can provide supportive evidence for the diagnosis.

Treatment

1. No specific treatment is indicated or effective; the condition resolves over 8–12 weeks.

2. In cases with severe pruritus, symptomatic treatments, such as antihistamines and mild topical corticosteroids, may be beneficial.

3. UVB phototherapy has been advocated to decrease the severity, particularly when administered early in the course. This treatment may worsen the postinflammatory dyspigmentation.

Alternative Diagnosis: Tinea Corporis

Textbook Presentation

Tinea corporis commonly presents as round, pink plaques with small peripheral papules and a rim of scales. The neck and back are the most common locations (Figure 29-12).

Disease Highlights

1. Description of the lesion: multiple lesions are possible.

   1. Circular lesions with a sharply marginated raised border and central clearing, arising by centrifugal spread of the fungus from the initial site of infection

   2. Inflammatory lesions may demonstrate pustules or vesicles, especially around the margin.

   3. Overlying scale is common, typically more prominent at the border of the lesion.

   4. Solitary lesions may occur, or there may be multiple plaques that remain discrete or become confluent.

2. The degree of associated inflammatory change is variable, depending on the causative species of fungus.

3. The wide variation in clinical presentation depends on the species of fungus, size of the inoculum, body site infected, and immune status of the patient.

Evidence-Based Diagnosis

1. Identification of the fungus by microscopic examination of scales after application of 5–20% potassium hydroxide

2. Culture of tissue material (such as the scale)

3. Histopathology is rarely necessary to make the diagnosis of a superficial infection, but with the use of fungal stains the cell walls may be visible in fixed sections.

Treatment

1. Both topical and systemic antifungal agents are effective.

2. Decision of which to use is based on the extent and location of the infection.

3. Hair-bearing sites often require systemic therapy.

Alternative Diagnosis: Nummular Dermatitis

Textbook Presentation

Nummular dermatitis generally presents as an extremely pruritic rash of numerous, round, crusted lesions on a patient’s legs.

Disease Highlights

1. Description of lesions: well-demarcated coin-shaped lesions composed of minute vesicles and papules on an erythematous base. The lesions have an overlying crust, frequently with a weeping exudate (Figure 29-13).

2. Nummular dermatitis is an acute eruption of numerous lesions predominantly on the extremities.

3. The lesions are severely pruritic.

4. The eruption runs a remitting and relapsing course.

5. Patients are often atopic.

6. Secondary infection is frequently present.

Evidence-Based Diagnosis

1. Microscopic examination of a scraping will rule out tinea.

2. Histopathology can assist in the diagnosis by demonstrating the features of an acute dermatitis.

Treatment

1. If present, secondary infections often require treatment with systemic antibiotics.

2. Antihistamines can help alleviate the pruritus.

3. Skin care, especially bathing practices and appropriate use of emollients, should be stressed.

4. Topical corticosteroids are useful for flares.

Alternative Diagnosis: Secondary Syphilis

Textbook Presentation

Secondary syphilis presents as oval macules in sexually active people. The lesions are present diffusely, including on the palms and soles. A history of a transient, painless, genital ulcer in the preceding weeks can often be obtained.

Disease Highlights

1. Description of lesion: papules and plaques distributed over the entire body. They are copper red to hyperpigmented in color.

2. Character of the lesion

   1. There may be variable lesions at different stages of disease.

      1. A fleeting eruption of symmetric, coppery red, round and oval macules may be seen early in the secondary stage, about 8 weeks after the infecting exposure.

      2. The later, classic eruption includes involvement of mucosal surfaces and palms and soles.

      3. In the latest phases, thick scales may cover the plaques.

   2. The rashes of secondary syphilis are nonpruritic.

   3. The lesions are generally symmetrically distributed.

Evidence-Based Diagnosis

1. The Venereal Disease Research Laboratories (VDRL) and fluorescent treponemal antibody (FTA) tests are 100% sensitive for secondary syphilis.

2. FTA tests have specificities in the high 90% range.

Treatment

Penicillin is the treatment of choice for secondary syphilis.

Guttate psoriasis affects those with a predisposition toward psoriasis. The guttate flares tend to remit quite reliably; however, affected individuals are at increased risk for the development of chronic psoriasis.

Urticaria

Textbook Presentation

Urticaria typically presents as an itchy rash with large or small, palpable, red areas over the entire body. The rash is transient, with no 1 lesion lasting very long. Both the rash and the pruritus respond to antihistamines.

Disease Highlights

1. Description of the lesion: transient pink to red gently elevated edematous papules and plaques that may coalesce into giant lesions. The lesions often leave purple discoloration or central clearing when they fade (Figure 29-14).

2. Characteristics of the lesion

   1. Individual lesions should resolve within 24 hours while new lesions may continue to develop.

   2. The eruption is typically accompanied by itch, but excoriations are rare.

3. Mucous membranes, eyelids, hands, and feet may develop deeper subcutaneous swelling manifesting as angioedema.

4. Most urticaria is acute, lasting less than 6 weeks.

5. Urticaria is a hypersensitivity reaction to numerous insults.

   1. Etiologic factors can be remembered with the mnemonic I-I-I-I-I.

      1. Infection

      2. Infestation

      3. Ingestion (food or drug)

      4. Inhalation

      5. Injection

   2. Idiopathic should probably be added to this list because the etiologic agent may induce an immunologic cascade that persists in the absence of the inciting agent.

6. Chronic urticaria (lasting > 6 weeks) can also be seen in the setting of systemic disease such as collagen vascular disease, malignancy, parasitosis, and chronic infection.

Evidence-Based Diagnosis

1. Clinical findings of typical transient urticaria are diagnostic, and a skin biopsy is rarely indicated.

2. The morphologic differential diagnosis often includes the following:

   1. Erythema multiforme (because of the targetoid appearance of some urticaria)

   2. Insect bite reactions

   3. The early phases of bullous pemphigoid

3. Urticaria can be distinguished from all of the above disorders because it is the only one with lesions that last < 24 hours.

4. A careful history, including review of medications, recent exposures, and food ingestion, is the most important aspect of the evaluation to determine a cause.

5. Laboratory evaluation is sometimes undertaken in cases of chronic urticaria, but studies have shown that relevant results are so rarely found without other symptoms that this approach is discouraged.

Treatment

1. Identification of the inciting agent (medication, supplement, infection) is paramount and should be addressed as the first step in management.

2. Antihistamines are the mainstay of therapy. H₁-blockers should be given on a regular dosing schedule until the eruption is suppressed and then tapered gradually to prevent rebound flare.

3. Combinations of different H₁-blockers can be effective when a single agent is inadequate.

4. Addition of H₂-blockers may be helpful in refractory cases.

Purpura/Petechiae

Textbook Presentation

Purpura and petechiae are seen in patients with bleeding diatheses or vascular damage. Petechiae are capillary hemorrhages that present as nonblanching, pinpoint, red spots over dependent body parts, most commonly the lower extremities. Purpura are larger hemorrhages into the skin.

Purpura are associated with a variety of life-threatening diseases such as vasculitis and sepsis.

Disease Highlights

1. Description of the lesion: petechiae are red, blue or purple, nonblanching, pinpoint spots. Purpura are larger (up to several centimeters) nonblanching macules, papules, or plaques that may or may not be palpable (Figure 29-15).

2. Both purpura and petechiae are, to some degree, nonblanching; (ie, the color cannot be compressed out of the lesion by pressure).

3. The shape of these lesions is variable, ranging from stellate to round or oval or targetoid to retiform (netlike).

4. The color, texture, and configuration of these lesions will be helpful in constructing a differential diagnosis of the cause.

5. The differential diagnosis of purpura/petechiae is vast, and many classification schemes have been proposed. The first step is to differentiate ecchymoses from purpura and petechiae.

6. Ecchymoses

   1. Ecchymoses are the most common form of hemorrhage in the skin.

   2. They are typically induced by trauma and, therefore, are seen on trauma-prone sites such as the dorsal hand, forearm, lateral thigh, and shin.

   3. The shape of ecchymoses tends to be geometric (rectangular) or linear because they are induced by an external force.

   4. Predisposing factors to ecchymoses include weakening of the dermal structure secondary to age, corticosteroid use, solar damage, and vitamin C deficiency (scurvy), as well as coagulation defects.

7. Petechiae are most commonly associated with thrombocytopenia.

8. Purpura

   1. Like petechiae, purpura signify hemorrhage into the skin.

   2. The hemorrhage may

      1. Be simple extravasation through leaky vessel walls.

      2. Be accompanied by inflammation that is damaging vessel walls. (These lesions are often partially blanching because the inflammatory component blanches while the hemorrhagic component does not.)

      3. Be the result of occlusion of a vessel leading to ischemic damage to the skin.

   3. The degree to which purpuric lesions are palpable is helpful diagnostically.

      1. Nonpalpable hemorrhage in the skin is most concerning for thrombocytopenia or abnormal platelet function.

      2. Extravasation of blood alone into deep tissue layers can produce a nodule (such as occurs with a hematoma).

      3. Edema associated with the vessel injury (such as in cases of inflammatory vasculitis) may cause a palpable lesion.

         • (1) Palpable purpura can be a sign of serious of illness.

         • (2) Evaluation should include tests for vasculitis and, in the right setting, infectious causes (possibly including empiric treatment).

Evidence-Based Diagnosis

1. An evaluation of clotting (platelet number, function and measures of coagulation) is indicated to determine if purpura and petechiae are symptoms of a coagulopathy, thrombocytopenia, or vasculitis.

2. A skin biopsy can be helpful in determining

   1. The size and location of affected vessels within the dermal and subcutaneous tissues.

   2. The degree and character of associated inflammation.

   3. The type of vessel damage (leukocytoclastic or granulomatous).

   4. The presence and character of any occlusions within vessels (organisms, calcium, fibrin).

3. Immunofluorescence studies of histologic specimens can be helpful in identifying antibody and complement deposits on vessels walls.

Treatment

1. Treatment is directed toward management of the underlying cause of the vessel damage.

2. Supportive therapy includes local wound care and prevention of secondary infection.

Skin Cancer

There are innumerable specific forms of skin cancer, deriving from all of the structures of the skin and subcutaneous tissues. In addition, many cancers will metastasize to the skin. The three most common skin cancers are described.

1. Basal Cell Carcinoma

Textbook Presentation

Basal cell carcinoma most commonly presents as a flesh-colored, translucent, or slightly red papule or nodule, classically displaying a rolled border. Most commonly presents on the head or neck of older adults.

Disease Highlights

1. Description of lesion: the typical lesion is a flesh-colored, translucent, or slightly red papule or nodule, classically displaying a rolled border (Figure 29-16).

   1. Lesions are often friable, bleeding easily and developing crust. Telangiectasias on the surface can be a helpful sign.

   2. Large tumors can be locally destructive.

2. Basal cell carcinoma is the most common malignant tumor in humans.

3. Lesions are typically asymptomatic except for the observation of easy bleeding from a site.

   1. Only rarely is pain associated.

   2. Metastasis from a basal cell carcinoma is rare.

4. Individuals at risk are adults with fair hair and eyes, easy freckling, and propensity for sunburn.

   1. Patients with skin of color are less likely to be affected.

   2. Men and women are about equally affected.

   3. Exposure to UV light has long been believed to play a causative role in the development of this tumor, although the exact mechanism is not clear. Several genetic mutations have been isolated in basal cell carcinoma and may serve as targets for therapeutics.

   4. Chronic wounds and sites of inflammation as well as immunosuppression can predispose to development of this tumor.

   5. Exposure to arsenic is another risk factor for basal cell carcinoma.

5. The head and neck are the most common sites affected with this tumor.

   1. Only 10–15% of tumors develop on sun-protected skin.

   2. The nose is the most common site, accounting for 20–30% of all cases.

6. Basal cell carcinoma is likely derived from the hair follicle. The name implies a resemblance of the tumor cells to the basal cells of the epidermis, although this is not believed to be their derivation.

7. Patients have up to a 45% risk of developing subsequent basal cell carcinomas in the 5 years after initial diagnosis.

Evidence-Based Diagnosis

Histologic evaluation of affected tissue is the gold standard for diagnosis.

Treatment

1. The goal of therapy is to eliminate the tumor and prevent local tissue destruction. Numerous methods are available to accomplish this goal, and selection depends on tumor size, type, and location, patient characteristics, and patient preferences.

2. 5-year recurrence rates vary by treatment modality. The lowest recurrence rate is achieved with Mohs micrographic surgery.

   1. This method involves excision of the visible tumor, followed by microscopic evaluation of frozen tissue sections to visualize tumor margins and repeat local excision until all margins are clear of tumor.

   2. The technique allows for maximal tissue sparing while ensuring complete eradication of tumor.

3. Follow-up of patients for recurrent or subsequent tumors is critical.

2. Squamous Cell Carcinoma

Textbook Presentation

Squamous cell carcinoma most commonly presents as a firm but somewhat indistinct nodule or plaque. It may evolve from actinic keratoses on the sun-exposed skin of middle-aged people.

Disease Highlights

1. Description of lesion: lesions are firm but somewhat indistinct nodules or plaques that may arise from an in situ carcinoma or in normal skin. Tumors may become ulcerated or bleed easily and become crusted (Figure 29-17).

   1. The surface may be smooth, verrucous, or papillomatous, with or without scaling.

   2. Fixation to underlying structures develops as the lesion invades locally.

   3. In situ lesions tend to be sharply demarcated erythematous scaling plaques.

2. This tumor most commonly affects fair-skinned individuals with excessive sun exposure.

   1. May evolve from actinic keratoses on sun-exposed skin in these patients.

   2. UV radiation is a major risk factor for the development of this tumor.

   3. Additional predisposing factors include

      1. Radiation therapy

      2. Chronic scar formation

      3. Chemical carcinogens, such as hydrocarbons

      4. Viral exposures

      5. Thermal exposures

      6. Arsenic

      7. Long-term immunosuppression (such as in kidney transplant recipients).

3. Squamous cell carcinoma does carry a risk of local recurrence and metastasis.

   1. The risk of local recurrence is around 3%.

   2. Metastasis is less common but can reach 10% in patients with the thickest lesions.

   3. Other factors, such as location (ears) and immunosuppression, are also associated with higher risk of metastasis.

4. Intraoral squamous cell carcinoma is predominantly a disease of adult men.

   1. Risk factors are alcohol and tobacco use.

   2. When detected in the early asymptomatic stage, these cancers are easily curable.

5. Incidence increases with age and varies with geographic location, ethnicity, and behavior patterns.

Evidence-Based Diagnosis

1. Histologic evaluation of affected tissue is the gold standard for diagnosis.

2. A high index of suspicion may be necessary to recognize a potential tumor when its appearance or location is unusual. For example, the verrucous form of squamous cell carcinoma can be mistaken for a wart.

Treatment

1. The goal of treatment is eradication of the tumor while producing the least disability and dysfunction for the patient.

2. Careful evaluation for the presence of metastatic disease is paramount. This may include lymph node dissection in some instances.

3. Multiple destruction modalities are available and are selected based on size, shape, and location of the tumor as well as patient preferences. These modalities include, but are not limited to

   1. Excisional surgery

   2. Mohs micrographic surgery

   3. Electrosurgery

   4. Radiation therapy

   5. Local immunotherapy

4. Wide destruction of these tumors usually results in cure as squamous cell carcinomas grow by direct extension. However, residual tumor can invade and extend along peripheral nerves, allowing a deep recurrence on occasion.

5. A large percentage of squamous cell carcinomas could be prevented by avoidance of excessive solar exposure. Routine screening for tumors, especially in high-risk patients, is imperative.

3. Melanoma

Textbook Presentation

Melanoma typically presents as a dark brown or black macule or papule in a middle-aged person. The lesion has pigment variation throughout and irregular borders.

Disease Highlights

1. Description of lesion: the most common type of melanoma is superficial spreading (Figure 29-18).

   1. These tumors may present as a dark brown to black macule or thin plaque, typically with pigment variation throughout and irregular borders.

   2. With growth, the surface becomes glossy.

   3. The most common location of superficial spreading melanomas is on the upper back in males and the leg in females.

2. These cancers are most commonly diagnosed in the fourth and fifth decades of life.

3. Melanoma may arise in a preexisting melanocytic nevus or de novo.

4. Multiple subtypes exist, including lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, acral lentiginous melanoma, and amelanotic melanoma among others.

   1. Nodular melanoma is the second most common type of melanoma.

      1. Presents most often on the head, neck, or trunk.

      2. These tumors evolve rapidly over months.

      3. They appear as a blue-black, reddish, purplish, or even a nonpigmented papule or nodule.

   2. Acral lentiginous melanoma is the predominant type of melanoma seen in the more pigmented races, such as Africans, Asians, and Indians.

      1. Acral lentiginous melanoma occurs on the palms and soles and beneath the nail plate.

      2. Diagnosis of these lesions is often delayed; therefore, they are often of a more advanced stage at diagnosis.

      3. Affected individuals tend to be older.

   3. Lentigo maligna melanoma is a rare type of melanoma found predominantly in the elderly on the sun-exposed portions of the head and neck.

      1. The tumor is usually flat, with irregular borders and a diameter of several centimeters.

      2. Color varies throughout from tan to brown to black and purple and blue.

5. Melanoma is a tumor of melanocytes.

   1. Benign pigmented nevi are composed of altered melanocytes, termed “nevomelanocytes.”

   2. Malignant transformation of melanocytes and nevomelanocytes can result in melanoma, arising de novo from normal skin, or from a preexisting nevomelanocytic lesion (nevus or mole).

6. The incidence of cutaneous melanoma is increasing steadily in the United States. In 1935, the lifetime risk of an American developing melanoma was 1 in 1500 individuals, whereas in 2013 the risk was 1 in 50 for white Americans, 1 in 1000 for black Americans and 1 in 200 for Hispanic Americans.

   1. In 2013, it is estimated that melanoma will be diagnosed in 76,690 Americans, and 9480 will die of the disease.

   2. Melanoma will be the fifth most common cancer among males and the seventh most common cancer among females.

7. Epidemiologic studies strongly suggest that sun exposure is a major risk factor for the development of cutaneous melanoma in the light-skinned populations.

   1. Intense intermittent episodes of sun exposure before 18 years of age are thought to engender the highest risk in susceptible populations.

   2. Phenotypic features have been associated with increased risk for cutaneous melanoma: light skin pigmentation, ease of sunburning, blond or red hair, prominent freckling, and blue or green eyes.

8. Familial melanoma accounts for 8–12% of cases. Those with at least 2 first-degree relatives with a history of melanoma are at particularly high risk.

9. Dysplastic nevi (clinically atypical appearing nevi) are thought to be markers of an individual with an increased risk of developing cutaneous melanoma.

   1. The number of nevi on the body has been directly correlated with the magnitude of melanoma risk.

   2. About one-third of melanomas have been associated with an underlying nevus.

10. Recurrences of disease generally occur in a stepwise manner, first locally, then in regional lymph nodes, and lastly as distant metastases.

Evidence-Based Diagnosis

1. An excisional biopsy is the preferred method for obtaining tissue for diagnosis. This preserves the extent of the primary tumor and all associated histologic features without disrupting the lymphatic architecture.

2. Full-thickness incisional or punch biopsies of lesions too large to excise fully or in anatomically sensitive locations are satisfactory.

3. The histologic diagnosis of melanoma is based on a constellation of features; no single feature is diagnostic. Both cytologic and architectural features are evaluated.

4. The staging system for melanoma focuses on tumor thickness and presence of ulceration as the most important initial prognostic variables in localized disease (stages I and II). Stage III has regional nodal involvement, and stage IV has distant metastases.

Treatment

1. Management of cutaneous melanoma is guided by stage of disease. Wide excision of tumors is the general rule.

2. Sentinel lymph node mapping may be beneficial diagnostically in more advanced stages, decreasing the complications associated with full lymph node dissections.

3. Adjuvant treatment options for advanced stage disease include interferon alpha-2b, radiation of nodal basins, chemotherapy, and other novel strategies such as tumor vaccines and immunotherapies.

4. Follow-up of melanoma patients is critical to detect recurrences as well as new primary tumors and to provide ongoing education.

5. Melanoma prevention strategies focus on education about the risks of UV exposure via sunlight or tanning machines, sun protection guidelines, and the importance of routine self-skin exams.

   1. Early detection is important for improving outcomes.

   2. Patients should be instructed on the importance of their own skin examination and what constitutes a worrisome mole, easily remembered by the ABCDEs of mole evaluation.

      1. A: asymmetry

      2. B: borders that are irregular or changing

      3. C: color that is irregular or changing

      4. D: diameter > 6 mm (or larger than a pencil eraser)

      5. E: evolution of the lesion in general