Section 18. Pigmentary and Light Related Conditions

A young Hispanic woman delivers a healthy baby boy. On the first postpartum day, she is sitting in the rocking chair after breastfeeding her son. Her doctor notes that she has melasma and asks her about it. She states that the hyperpigmented areas on her face have become darker during this pregnancy (Figure 197-1). She noted the dark spots started with her first pregnancy but they are worse this time. On physical examination, hyperpigmented patches are noted on the cheeks and upper lip (Figure 197-2). Although the patient hopes the pigment will fade, she does not want to treat the melasma at this time.

Melasma is an acquired hyperpigmentary disorder characterized by light- to dark-brown macules and patches occurring in the sun-exposed areas of the face and neck. It is most commonly caused by pregnancy or the use of sex steroid hormones, such as oral contraceptive pills.

Chloasma, mask of pregnancy.

• It is a relatively common disorder that affects sun-exposed areas of skin, most commonly the face. It is believed to affect up to 75% of pregnant women.1
• It affects predominantly women (Figures 197-1, 197-2, and 197-3), with men accounting for only 10% of all cases. It is particularly prevalent in women of Hispanic, East Asian, and Southeast Asian origin (skin types IV to VI) and who live in areas of intense UV radiation exposure.1
• Melasma caused by pregnancy usually regresses within a year, but areas of hyperpigmentation may never completely resolve.2 It may increase with each subsequent pregnancy becoming more obvious.

The major etiologic factors include genetic influences, exposure to UV radiation, and sex hormones.

• The precise cause of melasma has not been determined. Multiple factors have been implicated, including pregnancy, oral contraceptives, genetics, sun exposure, cosmetic use, thyroid dysfunction, and antiepileptic medications.3,4
• Women with melasma not related to pregnancy or oral contraceptive use may have hormonal alterations that are consistent with mild ovarian dysfunction.
• Melasma in men (Figure 197-4) shares the same clinical features as in women, but it is not known if hormonal factors play a role.5

Other factors associated with melasma include certain cosmetic ingredients (oxidized linoleic acid, salicylate, citral, preservatives) and certain antiepileptic drug. Some medications or topical preparations in combination with sun exposure worsen melasma.1

A recent global survey of 324 women with melasma demonstrated that a combination of the known triggers, including pregnancy, hormonal birth control, family history, and sun exposure, affects onset of melasma.6

Clinical Features

The diagnosis of melasma is based upon clinical appearance. Affected patients exhibit splotchy areas of hyperpigmented macules on the face (Figures 197-1, 197-2, 197-3, and 197-4). In natural light, epidermal melasma appears light to dark brown, and the dermal pattern is blue or gray.

Melasma is divided into four clinical types:

1. Epidermal type—The hyperpigmentation is usually light brown, and Wood's light enhances the color contrast between hyperpigmented areas and normal skin. It is the most common type, and it best responds to the use of depigmenting agents.

2. Dermal type—The hyperpigmentation is ashen or bluish-gray and exhibits no accentuation of color contrast under Wood's light. Depigmenting agents are generally not effective for this type.

3. Mixed type—The hyperpigmentation is usually dark brown, and Wood's light enhances the color contrast in some areas but not in others.

4. Indeterminate type—Presents in patients with darker complexions (skin types V to VI) and cannot be categorized under Wood's light.1

The lesion is found typically on sun-exposed areas. The three typical patterns of involvement are:

1. Centrofacial involving the cheeks, forehead, upper lip, nose, and chin.

2. Malar involving the cheeks and nose.

3. Mandibular involving the ramus of the mandible.

Imaging

A Wood's light may be used to determine the type of melasma.1 This does not change the choices of standard topical therapies.

Biopsy

Histologically, there are an increased number of melanocytes, with the deposition of additional melanin and a background of solar elastosis. The two main histologic patterns are epidermal and dermal, depending on the skin layers involved.

• The facial rash of systemic lupus may be confused with melasma as they both can have a butterfly pattern. Melasma is hyperpigmented, whereas the lupus facial rash is usually inflammatory. An antinuclear antibody (ANA) test should be positive in systemic lupus erythematosus (SLE) and negative in melasma. False-positive antinuclear antibodies are usually low titer and the patient does not have other criteria for lupus (see Chapter 180, Lupus Erythematosus).
• Discoid lupus or cutaneous lupus can occur across the face but is usually seen with scarring. In this condition, the ANA is often negative (see Chapter 180, Lupus: Systemic and Cutaneous).
• Contact dermatitis will be inflamed in the acute stage but the postinflammatory hyperpigmentation could be confused with melasma (see Chapter 146, Contact Dermatitis).

The treatment of melasma is challenging because treatment for melasma is generally unsatisfactory.7 Numerous less-than-adequate treatment options exist, including topical agents and chemical peels. Melasma treatment is started only when the patient is disturbed by the hyperpigmentation. All patients can benefit from sun protection and this is always a good place to start.

It is important to give the patient realistic treatment goals. The treatments that follow may lighten the hyperpigmentation but do not generally remove all the hyperpigmentation.

Side effects of all topical treatments include contact dermatitis, ­depigmentation of surrounding normal skin, and postinflammatory hyperpigmentation. Tretinoin should not be used during pregnancy. Discontinue oral contraceptives or other estrogen/progesterone agents, if possible.

Medications

• Hydroquinone is the main bleaching agent used to treat melasma.7 SOR A It is available over the counter in 2% or 3% formulations (some including sunscreens). The prescription strength is 4% and is available with or without a sunscreen. Generic 4% hydroquinone comes in many sizes and formulations, so write the prescription to be flexible to avoid hassles for you and the patient. Although hydroquinone with sunscreen may be somewhat better than ­hydroquinone alone, a combination product has not been shown to be better than using these two topical agents together as two separate products. SOR C
• Hydroquinone is applied twice daily for up to 3 months with subsequent tapering to once daily. If the patient has not noticed a benefit by 3 months, the treatment should be stopped. SOR C
• Ochronosis—If the skin becomes darker with treatment, then the hydroquinone should be discontinued as there is a known side effect of hydroquinone, called ochronosis, that causes hyperpigmentation. Ochronosis only occurs in the treated area, but the hyperpigmentation can be permanent.8
• Hydroquinone can also cause a contact dermatitis, so it is a good idea for the patient to try it on a small area of skin before applying it to large areas of the face. Hydroquinone should be avoided on inflamed skin to avoid additional postinflammatory hyperpigmentation.
• Tretinoin 0.1% (Retin-A) cream is applied once daily at bedtime to lighten melasma. In two studies where tretinoin was compared to placebo, participants rated their melasma as significantly improved in one but not the other. In both studies, by other objective ­measures, tretinoin treatment significantly reduced the severity of melasma.7 SOR A
• Combining tretinoin and hydroquinone is believed to potentiate their effects. SOR C
• There is a triple combination cream (Tri-Luma) containing 4% hydroquinone, retinoic acid, and fluocinolone (corticosteroid). It is used once daily before bed for a duration of 8 weeks. Studies show that it has a superior efficacy than hydroquinone monotherapy for melasma.9,10 SOR A However, the side effect of skin irritation is very common and it is not recommended for long-term use.9,10 Triple-combination cream was significantly more effective at lightening melasma than hydroquinone alone (relative risk [RR]1.58) or when compared to the dual combinations of tretinoin and hydroquinone (RR 2.75).7 SOR A
• Note that Tri-Luma is very expensive. Individual prescriptions for 4% hydroquinone, tretinoin cream, and a mild topical steroid cream can be given to keep the cost down. Desonide or 1% hydrocortisone are good options for the topical steroid. The steroid should not be used daily for longer than 8 weeks to avoid adverse effects.
• Azelaic acid (20%) was significantly more effective than 2% hydroquinone at lightening melasma but not better than 4% hydroquinone.7 SOR A
• Kojic acid formulations, and α-hydroxy acids (such as glycolic acid) also have been used in the treatment of melasma. SOR C
• The adverse events most commonly reported with topical agents were mild and transient such as skin irritation, itching, burning, and stinging.7 SOR A

Surgical Procedures

• Chemical peels are one option for patients with moderate to severe melasma that has not responded to bleaching agents and are seeking further treatment. SOR C
• Dermabrasion treatment is one aggressive option.11 SOR C
• Q-switched pigmentary lasers, intense pulsed light, and fractional laser treatments have some efficacy but can cause postinflammatory hyperpigmentation and relapses may occur so are usually not recommended.12 SOR C

Strict avoidance of sun exposure is important to prevent further hyperpigmentation. SOR C Broad-spectrum, high-protection-factor sunscreens (with UVB and UVA protection), such as titanium dioxide, micronized zinc oxide, Mexoryl, or avobenzone/Parsol, are essential.13

Follow-up is advisable when using bleaching agents. Long-term ­follow-up and reinforcement of limiting sun exposure can be ­accomplished during routine prevention visits.

• Provide the patient with realistic treatment goals.
• If the topical medications are irritating the skin, stop them and return for further evaluation.
• If after 3 months hydroquinone has not worked, stop it.
• If the skin is darkening rather than lightening, stop the medications and return for further evaluation.
• Bleaching agents are often not covered by insurance. The price of hydroquinone formulations can vary widely, so it helps to shop around when cost is a major concern.

Patient Resources

• WebMD. Skin Problems of Pregnancy—http://www.webmd.com/baby/skin-conditions-pregnancy.
• American Pregnancy Association. Skin Changes During Pregnancy— http://www.americanpregnancy.org/pregnancyhealth/skinchanges.html.
• WebMD. Cosmetic Procedures, Birthmarks, and Other Abnormal Skin Pigmentation—http://www.webmd.com/healthy-beauty/cosmetic-procedures-birthmarks.
• WebMD. Hyperpigmentation, Hypopigmentation, and Your Skin—http://www.webmd.com/skin-problems-and-treatments/guide/hyperpigmentation-hypopigmentation.

Provider Resources

• American Academy of Family Physicians. Common Hyperpigmentation Disorders in Adults: Part II—http://www.aafp.org/afp/20031115/1963.html.
• Kang HY, Ortonne JP. What should be considered in treatment of melasma. Ann Dermatol. 2010;22(4):373-378—http://pdf.medrang.co.kr/Aod/022/Aod022-04-01.pdf.

An 8-year-old Hispanic boy is brought in to the clinic by his mother, who is concerned about his pigment loss (Figure 198-1). He is starting to develop this vitiligo around the eyes, and his mother wants him to be treated. The child was started on a topical steroid, and the use of narrow band UVB was discussed if the steroid does not prove helpful. Realistic expectations of the treatments were provided to the mother and her son.

Vitiligo is an acquired, progressive loss of pigmentation of the epidermis. The Vitiligo European Task Force defines nonsegmental vitiligo as “an acquired chronic pigmentation disorder characterized by white patches, often symmetrical, which usually increase in size with time, corresponding to a substantial loss of functioning epidermal and sometimes hair follicle melanocytes.”1 Segmental vitiligo is defined similarly except for a unilateral distribution that may totally or partially match a dermatome; occasionally more than one segment is involved.1

Vitiligo vulgaris.

• Vitiligo occurs in approximately 0.5% to 2% of the worldwide population.2,3
• It can occur at any age but typically develops between the ages of 10 and 30 years.2
• Vitiligo has equal rates in men and women.2
• It occurs in all races but is more prominent in those with darker skin.

• Autoimmune disease with destruction of melanocytes.
• Genetic component in approximately 30% of cases. Toll-like receptor genes were found to be associated with vitiligo in a ­population of Turkish patients.4
• Can trigger or worsen with illness, emotional stress, and/or skin trauma (Koebner phenomenon).

Clinical Features

• Macular regions of depigmentation with scalloped, well-defined borders (Figures 198-1, 198-2, and 198-3).
• Depigmented areas often coalesce over time to form larger areas (Figures 198-4 and 198-5).
• Depigmented areas are more susceptible to sunburn. Tanning of the normal surrounding skin makes the depigmented areas more obvious.
• There is no standardized method for assessing vitiligo; strategies include subjective clinical assessment, semiobjective assessment (e.g., Vitiligo Area Scoring Index [VASI] and point-counting methods), macroscopic morphologic assessment (e.g., visual, photographic in natural or UV light, computerized image analysis), micromorphologic assessment (e.g., confocal laser microscopy), and objective assessment (e.g., software-based image analysis, tri­stimulus colorimetry, spectrophotometry).5 Authors of a literature review concluded that the VASI, the rule of 9, and Wood's lamp were the best techniques for assessing the degree of pigmentary lesions and measuring the extent and progression of vitiligo.5
• Conditions associated with vitiligo include thyroid disease and the presence of thyroid antibodies,6,7 congenital nevi (in one study, 6.2% vs. 2.8% in those without vitiligo),4 and halo nevi,1 and possibly primary open-angle glaucoma (57% of patients in one case series).8

Typical Distribution

• Widespread, but generally seen first on the face, hands, arms, and genitalia (Figure 198-6).
• Depigmentation around body openings such as eyes, mouth, umbilicus, and anus is common (Figure 198-7). When the eyelashes are involved it is called leukotrichia.
• Vitiligo can be unilateral or bilateral; in one study, patients with unilateral vitiligo were younger and had an earlier age at onset while those with bilateral vitiligo were more likely to have light skin types and more commonly had associated autoimmune disease.9

Laboratory and Imaging

• Evaluation for endocrine disorders such as hyper- or hypothyroidism (e.g., thyroid-stimulating hormone [TSH]) and diabetes mellitus (e.g., fasting blood sugar) is indicated, as vitiligo can be associated with these disorders.10
• Pernicious anemia and lupus erythematosus should be considered; obtain complete blood count (CBC) with indices and an antinuclear antibody (ANA).

Biopsy

Not indicated unless the diagnosis is not clear and then a 4-mm punch biopsy will suffice.

• Pityriasis alba—Areas of decreased pigmentation with scaling and mild itching. Seen in young children and usually associated with eczema and improves with age (see Chapter 145, Atopic Dermatitis).
• Ash leaf spots—Lance-shaped macules of hypopigmentation, which remain stable in size and shape over time (Figure 198-8). Often the earliest sign of tuberous sclerosis. More concerning if there are 3 or more present in one child.
• Halo nevus—Hypopigmentation confined to areas surrounding pigmented nevi that typically appear in adolescents and young adults (see Chapter 162, Benign Nevi).
• Idiopathic guttate hypomelanosis—Confetti-like 2- to 5-mm areas of depigmentation predominantly on sun-exposed areas (Figure 198-9).
• Nevus depigmentosus is usually present at birth or starts in early childhood. There is a decreased number of melanosomes within a normal number of melanocytes. It typically has a serrated or jagged edge. Its presence at birth or early in childhood helps to differentiate it from vitiligo (Figure 198-10).
• Nevus anemicus—A congenital hypopigmented macule or patch that is stable in relative size and distribution. It occurs as a result of localized hypersensitivity to catecholamines and not a decrease in melanocytes. On diascopy (pressure with a glass slide) the skin is indistinguishable from the surrounding skin. Its presence from birth helps distinguish it from vitiligo (Figure 198-11).
• Hypomelanosis of Ito is a rare syndrome with hypopigmented whorls of skin present at birth along the Blaschko lines of development. This pattern may be accompanied by congenital abnormalities involving the eyes, or neurologic or renal systems. Its presence at birth helps distinguish it from vitiligo (Figure 198-12).

For assessing outcomes to treatment, the Vitiligo European Task Force suggests a system combining analysis of extent using percentage of body area involved (rule of 9), stage of disease based on cutaneous and hair pigmentation in vitiligo patches and staged 0 to 4 (with 0 representing normal pigment and 4 complete hair whitening) on the largest macule in each body region except hands and feet, and disease progression (spreading) assessed with Wood's lamp examination of the same largest macule in each body area.1 An evaluation sheet can be found in the citation.1

Nonpharmacologic

• Addressing the psychological distress that this disfiguring skin ­disorder causes should be a primary focus as the clinical course is unpredictable and, in some cases, little can be done to modify the condition itself.
• Management of inciting factors such as illness, stress, and skin trauma may be useful. SOR C

Medications

Topical treatments used for vitiligo include corticosteroids, immunomodulators, vitamin D analogs, and psoralens; these treatments had mixed outcomes based on a systematic review, with topical steroids having the highest rate of adverse events.11 SOR B Ineffective topical agents include melagenina, topical phenylalanine, topical L-DOPA (levodopa), coal tar, anacarcin forte oil, and minoxidil.12

• In a retrospective study of 101 children with vitiligo treated with moderate- to high-potency topical corticosteroids 64% (45/70) had repigmentation of the lesions, 24% (17/70) showed no change, and 11% (8/70) were worse than at the initial presentation.13 SOR B Local steroid side effects were noted in 26% of patients at 81.7 ± 44 days of follow-up. Two children were given the diagnosis of steroid-induced adrenal suppression. Children with head and/or neck affected areas were eight times more likely to have an abnormal cortisol level compared with children who were affected in other body areas.13 Therefore, a trial of topical steroids may be useful for patients with localized vitiligo that does not predominantly involve the head and neck. SOR C
• Based on several reviews, topical corticosteroids (potent or very potent) are the preferred drugs for localized vitiligo (<20% of skin area)11,12; a less-than-2-month trial is recommended.12 SOR B
• Topical immunomodulators (tacrolimus, pimecrolimus) are an alternative for localized vitiligo and display comparable effectiveness with fewer side effects.14 SOR B
• In a small case series (N = 6), various antitumor necrosis factor α agents (infliximab, etanercept, and adalimumab given according to treatment regimens used for psoriasis) were not effective for widespread nonsegmental vitiligo.15

Complementary and Alternative Therapy

• Antioxidants may be useful adjunctive therapy.11

Other Treatment

• Use sunscreen to prevent burns to the depigmented areas and further trauma to unaffected skin, and to minimize contrast between these areas.14 SOR A
• Bleaching the unaffected skin in patients with widespread depigmentation to reduce contrast with depigmented areas can improve cosmetic appearance.14 SOR B A monobenzylether of hydroquinone 20% cream (Benoquin) is available by prescription to produce a permanent bleaching of the skin around the vitiligo. It is irreversible and makes the skin at higher risk for sunburn.

Procedures

• Combination therapies are likely to be more effective than monotherapy, and most combinations include a form of phototherapy; narrow-band UVB appears to be the most effective with the fewest adverse effects (Figure 198-13).11,14 SOR B Psoralen UVA (PUVA) is the second-best choice. Authors of a Cochrane review concurred that majority of analyses showing statistically significant differences in treatment outcomes were from studies that assessed combination interventions including some form of light treatment.16
• Excimer laser is an alternative to UVB therapy, achieving good responses especially in localized vitiligo of the face, where the excimer laser may be superior to UVB therapy. By combining with topical immunomodulators, treatment response can be accelerated.14 SOR B In one prospective study of 14 patients, repigmentation rates for once, twice, and thrice weekly treatment approached each other (60%, 79%, and 82%, respectively) at 12 weeks. 17 Although repigmentation occurred fastest with thrice weekly treatment, the final repigmentation depends on the total number of treatments, not their frequency. SOR B
• No single therapy for vitiligo can be regarded as the most effective as the success of each treatment modality depends on the type and location of vitiligo. SOR B

The course of vitiligo varies, but is usually progressive with periods of activity interspersed with times of inactivity.18 Spontaneous repigmentation can occur but is rare.

• The face and neck respond best to all therapeutic approaches, while the acral areas are least responsive.14 SOR B
• Vitiligo does not appear to be associated with adverse outcomes in pregnancy.19

• Counseling and emotional support are a mainstay of follow-up treatment.
• Trials of various combination therapies may be needed.

• Reassurance that this is a benign condition while acknowledging any psychological distress.
• Advise patients about the highly variable course of vitiligo with usually progressive periods of activity interspersed with times of inactivity.
• Inform patients about the multiple treatment options and possible need for prolonged or repeat treatment.

Patient Resources

• National Institutes of Health. Vitiligo—http://health.nih.gov/topic/Vitiligo.
• National Organization for Albinism and Hypopigmentation—http://www.healthfinder.gov/orgs/HR2242.htm.
• National Vitiligo Foundation—http://nvfi.org/index.php.
• MedLine Plus. Vitiligo—http://www.nlm.nih.gov/medlineplus/ency/article/003224.htm.

Provider Resources

• Medscape. Vitiligo—http://emedicine.medscape.com/article/1068962.
• National Vitiligo Foundation. A Handbook for Physicians—http://nvfi.org/pages/info_physician_handbook.php.

A 50-year-old woman presented to the clinic with an abrupt onset of an intensely pruritic rash that extended over the dorsal aspect of both arms (Figure 199-1). The patient notes no new medicines and no recent exposures to any new chemicals. She acknowledged recent time spent outside in the sun. The plaques were photodistributed, with sparing of her watch area. A clinical diagnosis of polymorphous light eruption (PMLE) was made, and the patient was started on oral antihistamines and topical steroids. It was recommended that she minimize her sun exposure.

Photosensitivity is an abnormal skin response to ultraviolet light that occurs on sun-exposed areas of the skin. There are three common types of photodermatitis:

• PMLE (Figures 199-1 and 199-2).
• Phototoxic eruptions (Figures 199-3, 199-4, 199-5, 199-6, and 199-7).
• Photoallergic eruptions (Figure 199-8). Table 199-1 compares key characteristics of phototoxic and photoallergic reactions.

UV light radiating from the sun may be categorized into UVA (wavelength 320 to 400 nm), UVB (290 to 320 nm), and UVC (200 to 290 nm). UVC is completely absorbed by the earth's ozone layer and thus does not play a role in photosensitivity. Photosensitivity may be induced by UVA, UVB, or visible light (400 to 760 nm). Longer wavelength light penetrates deeper into the skin. UVA penetrates through to the dermis, but UVB mainly penetrates and affects the epidermis.

Ultraviolet light has multiple effects on the skin. Notably, it causes DNA damage and has immunosuppressive effects on skin inflammatory cells increasing the risk of carcinogenesis. In patients with photosensitivity, it elicits an inflammatory response in the skin, leading to the development of a photodermatosis.

• PMLE (Figures 199-1 and 199-2) may affect up to 10% of the population, with a predilection for females.1 The prevalence increases in northern latitudes. Onset typically occurs within the first three decades of life, but may appear spontaneously at any age.
• The incidence of drug- and plant-induced phototoxic reactions in the United States is unknown. Phototoxic reactions are much more common than photoallergic reactions.

PMLE is an idiopathic, delayed-type hypersensitivity reaction to UVA light and, to a lesser extent, UVB light (Figures 199-1 and 199-2). PMLE is the most common photoeruption encountered in clinical practice. The reaction will remit spontaneously with time and absence of sun exposure, but occasionally it will last as long as sun exposure occurs. PMLE usually begins in the first three decades of life and occurs more commonly in women. The rash develops within hours to days after exposure to sunlight and lasts for several days to a week.

There is a broad range of degrees of photosensitivity with PMLE. Extremely sensitive individuals can tolerate only minutes of exposure, whereas many people have a low sensitivity and require prolonged ­exposure to sunlight before developing a reaction. It is a recurrent condition that persists for many years in most patients.2

Phototoxic reactions are the most common drug-induced photoeruptions (Figures 199-3, 199-4, 199-5, 199-6, and 199-7). They are caused by absorption of ultraviolet rays by the causative drug, which releases energy and damages cell membranes, or, in the case of psoralens, DNA. The drugs that most frequently cause phototoxic reactions are NSAIDs, quinolones, tetracyclines, amiodarone, and the phenothiazines3 (Table 199-2). Most of these drugs have at least one resonating double bond or an aromatic ring that can absorb radiant energy. Most compounds are activated by wavelengths within the UVA (320 to 400 nm) range, although some compounds have a peak absorption within the UVB or visible range.

Phytophotodermatitis are phototoxic reactions to psoralens, which are plant compounds found in limes, celery, figs, and certain drugs. They can cause dramatic inflammation and bullae where the psoralen comes into contact with the skin (Figures 199-5, 199-6, and 199-7). The inflammation is frequently followed by hyperpigmentation.

Photoallergic eruptions are a lymphocyte-mediated reaction. Photoactivation of a drug or agent results in the development of a metabolite that can bind to proteins in the skin to form a complete antigen. The antigen is presented to lymphocytes by Langerhans cells, causing an inflammatory response and spongiotic dermatitis (eczema). The eruption is characterized by widespread eczema in the photodistribution areas such as the face, upper chest, arms, and back of hands (Figure 199-8). Most photoallergic reactions are caused by topical agents such as antibiotics and halogenated phenolic compounds added to soaps and fragrances.4 Systemic photoallergens such as the phenothiazines, chlorpromazine, sulfa products, and NSAIDs can produce photoallergic reactions, although most of their photosensitive reactions are phototoxic (Table 199-3).

Unprotected exposure to sunlight and the use of drugs associated with phototoxic and photoallergic eruptions are the main risk factors.

Clinical Features

Most cases of photodermatitis can be diagnosed on the basis of the patient's history. Be sure to review the patient's medications for possible sources.

• The appearance of the PMLE varies from person to person but is consistent in a given patient. Erythematous pruritic papules, sometimes with vesicles, are most common (Figures 199-1 and 199-2). Lesions may coalesce to form plaques. The rash typically involves the V of the neck and the arms, legs, or both. The face, which is exposed to sunlight in both summer and winter, tends to be spared. It tends to present in spring/summer, with the first significant UV exposure of the year. The rash typically develops 1 to 4 days after sun exposure.
• Phototoxic reaction occurs 2 to 6 hours after exposure to sunlight. The eruption typically appears as an exaggerated sunburn, with mild cases causing slight erythema and severe cases causing vesicles or bullae (Figures 199-3, 199-4, 199-5, 199-6, and 199-7).
• Phytophotodermatitis reactions are asymmetric and localized to the area in which the plant psoralen was in contact with the skin. Accompanying hyperpigmentation is a good clue to a phytophotodermatitis reaction (Figures 199-5, 199-6, and 199-7). Ask the patient if he or she had any contact with limes, celery, or figs. Squeezing lime juice into drinks is a particularly common cause of this reaction.
• Photoonycholysis phototoxicity reactions (sun-induced separation of the nail plate from the nail bed) have been reported with the use of tetracycline, psoralen, chloramphenicol, fluoroquinolones, oral contraceptives, quinine, and mercaptopurine. Photoonycholysis may be the only manifestation of phototoxicity in individuals with heavily pigmented skin.
• Photoallergic eruptions are characterized by widespread eczema in the photodistribution areas such as the face, upper chest, arms, and back of hands. They resemble allergic contact dermatitis, but the distribution is mostly limited to sun-exposed areas of the body (Figure 199-8).

Typical Distribution

• All photodermatitis reactions occur in sun-exposed areas, such as the face, ears, dorsal forearms, and V-area of the neck and upper chest.

Laboratory Testing

• Laboratory studies that may be helpful include antinuclear antibody (ANA), anti-Ro (SSA), and anti-La (SSB) titers to rule out lupus and porphyrin studies to exclude porphyria.
• Phototesting can be used to determine a patient's minimal erythema dose to light exposure and help to define the inciting spectrum of a photodermatosis (UVA versus UVB versus visible light). Phototesting involves irradiating the skin with varying doses of UVA, UVB, and visible light through an opaque screen with multiple openings.5 Usually the test is performed on the back. The presence or absence of solar urticaria is recorded within the first hour and the minimal erythema dose is determined after 24 hours.
• Provocative phototesting involves irradiating normal-appearing previously affected skin with the suspected causative light, either by higher doses of UV light or by natural sunlight exposure.5 Provocative phototesting is primarily used for suspected PMLE.
• Photopatch testing is useful when a topical photoallergen is suspected. It is performed by placing two identical sets of potential photoallergens on the patient's back and covering them. After 24 hours, one set is removed and that site is irradiated with UVA. The site is covered again. Twenty-four hours later, both the irradiated and control test sites are assessed for reactions. A reaction to a specific photoallergen in the irradiated site, but not the control site, indicates a photoallergy. A similar reaction in both sites suggests a contact dermatitis.5

Biopsy

• Punch biopsy of PMLE demonstrates extensive spongiosis and edema of the dermis with a deep lymphohistiocytic infiltrate. In acute phototoxic reactions, necrotic keratinocytes are observed.

• Systemic lupus erythematosus (SLE)—Sunlight can precipitate a lupus rash. Serum ANA is usually positive (see Chapter 180, Lupus: Systemic and Cutaneous).
• Porphyria cutanea tarda reactions can also be precipitated by sunlight. It tends to present with vesicles or bullae in sun-exposed areas such as the back of the hands. The bullae generally do not have any surrounding erythema, and urine for porphyrins should be positive (see Chapter 186, Other Bullous Disease).
• Dermatomyositis may cause an erythematous or violaceous eruption in sun-exposed areas. If these cutaneous findings precede the muscle weakness it can appear to be a photosensitivity reaction such as PMLE or a phototoxic drug reaction. Therefore, it is essential in the management and follow-up of patients with suspected PMLE or other photosensitivity to inquire about muscle weakness and to look for other signs of dermatomyositis on the hands and/or through laboratory tests for muscle enzyme elevations (see Chapter 181, Dermatomyositis). The dermatomyositis patient story in Chapter 181 is one in which the initial rash was thought to be a photosensitivity reaction to a new hydrochlorothiazide (HCTZ) prescription.
• Contact dermatitis appears the same as photoallergic dermatitis but is usually not limited to sun-exposed areas (see Chapter 146, Contact Dermatitis).

Nonpharmacologic

• The management of PMLE is aimed mainly at prevention. Patients who have mild disease should adopt a program of sun avoidance (see “Prevention” below). Broad spectrum (UVA and UVB blocking) sunscreen with a minimum sun protection factor (SPF) of 30 should be used whenever out of doors (Table 199-4).6 However, the SPF value of a sunscreen describes its protection factor against sunburn, which is primarily caused by UVB. The SPF does not provide sufficient information on UVA protection.7 SOR C Patients must use sunscreen liberally and frequently (reapply every 2 hours and after swimming) as an insufficiently thick application may reduce its effectiveness.8 SOR B
• Patients with severe PMLE can be desensitized in the spring with the use of phototherapy and maintained in the nonreactive state with weekly 1 hour unprotected exposure to sunlight. SOR C A course of psoralen and UVA radiation, or a course of narrow-band UVB, 3 times a week for 4 weeks provides protection.9 SOR B These treatments may induce a typical rash or erythema but otherwise have no major adverse effects.
• Avoid tobacco products since they may make PMLE worse.10 SOR B

Medications

• Acute episodes of photodermatitis respond rapidly to topical and/or oral corticosteroids. Topical steroids should provide symptomatic relief and decrease the inflammation. For more severe reactions, a course of prednisone 30 mg daily for 5 to 7 days may be used.11 SOR B
• Patients with acute drug-induced photodermatitis need to practice sun avoidance until well after the drug is discontinued. Topical and systemic corticosteroids may be used, especially with photoallergic reactions, but their efficacy is unproven. SOR C
• Nicotinamide was successful in 60% of 42 patients treated with 3 g/day orally for 2 weeks.12 SOR B

Sun protection is the primary preventative measure for patients with photosensitivity. Patients should avoid exposure to midday sun (between 10:00 am and 3:00 pm). Protective clothing such as long sleeve shirts and broad rim hats should be worn while outdoors. Fabrics that are tightly woven, thick, and/or dark-colored are useful for protection.14 Clothing treated with broad-spectrum UV absorbers is also helpful. Window film that blocks UV and some visible light can be applied to cars or homes.15

Sunscreen is important for daily use for patients with photosensitivity. Sunscreens are divided into chemical (organic) and physical (inorganic) products. Physical sunscreens block both UV and some visible light (see Table 199-4). Products containing avobenzone or ecamsule offer improved protection against UVA.

Physical blocker (inorganic) sunscreens, such as titanium dioxide and zinc oxide, work by reflecting and scattering UV and visible light. Older formulations were opaque making them cosmetically less acceptable to patients. Newer nonopaque, micronized formulations of titanium and zinc oxide have been developed but are less capable of scattering visible light and the longer wavelengths of UVA.

Chemical sunscreens may cause allergic contact dermatitis or photoallergic reactions in some patients. These patients should use titanium dioxide or zinc oxide sunscreens for protection.

• Some patients with PMLE experience less-severe reactions with successive years, but they may also worsen over time without appropriate treatment.
• The prognosis is excellent with patients when the offending agent is removed. Complete resolution of the photosensitivity may take weeks to months. Patients with persistent light reactivity beyond this have a poorer prognosis.

• Follow-up is needed if the photosensitivity persists.

• Patients with any type of photodermatitis should apply strong broad-spectrum sunscreens daily and use protective clothing (hats and shirts that cover the arms and V-neck). The sunscreen should be water resistant and applied to exposed areas before sun exposure.16 Sunscreens should be reapplied every 2 hours if there is continued sun exposure. Some of the most effective sunscreens contain stabilized avobenzone, Mexoryl, and/or titanium dioxide or zinc oxide to block UVA and UVB.
• Tell your patients that if they develop an allergy to one sunscreen, they should find another with different ingredients.
• It is important to avoid sunlight during the midday whenever possible.
• Explain to patients that phototoxic reactions may cause hyperpigmentation, which can take weeks to months to resolve. There is no guarantee that all the hyperpigmentation will go away.
• Avoid repeated rubbing and scratching, which can lead to skin thickening and chronic lichenification. Use the topical medications prescribed to treat the itching and to avoid lichenification.

Patient Resources

• DermNet NZ. Photosensitivity (Sun Allergy)—http://dermnetnz.org/reactions/photosensitivity.html.
• The Skin Cancer Foundation. Photosensitivity—A Reason To Be Even Safer in the Sun—http://www.skincancer.org/photosensitivity-a-reason-to-be-even-safer-in-the-sun.html.

Provider Resources

• American Academy of Family Physicians. Common Hyperpigmentation Disorders in Adults: Part I—http://www.aafp.org/afp/20031115/1955.html.
• eMedicine. Drug-Induced Photosensitivity—http://emedicine.medscape.com/article/1049648.
• DermNet NZ. Polymorphic Light Eruption—http://www.dermnetnz.org/reactions/pmle.html.
• Darby-Stewart AL, Edwards FD, Perry KJ. Hyperpigmentation and vesicles after beach vacation. Phytophotodermatitis. J Fam Pract. 2006;5512:1050-1053.
• Phytophotodermatitis case report and review—http://www.skinandaging.com/content/what-caused-this-rash-on-this-man%E2%80%99s-wrist-and-hand.
• eMedicine. Sunscreens and Photoprotection—http://emedicine.medscape.com/article/1119992.

A 50-year-old woman presented to the office with bilateral erythematous lesions on the inner aspects of both of her lower extremities (Figures 200-1 and 200-2). The lesions started developing for the past 6 months. They became progressively more noticeable but stayed localized in the inner aspects of the lower extremities. She mentioned that she was using a hot-water bottle in the area involved to keep her warm at night when she was sleeping in bed. Although our working clinical diagnosis was erythema ab igne, clinical entities such as livedo reticularis, poikiloderma atrophicans vasculare, and acanthosis nigricans were also considered in the differential diagnosis. A skin biopsy was performed and confirmed the diagnosis of erythema ab igne. The patient was advised to abandon the hot-water bottle application to the skin. Over the course of 4 months her skin lesions started to clear with no further intervention.

Erythema ab igne is a rare condition caused by chronic exposure to heat (below the threshold for a thermal burn) from external heat sources. More specifically, prolonged use of hot-water bottles, heating pads, electric blankets, car seat warmers as well as exposure to open fires and laptops placed on the users' thighs or propped legs have all been reported to cause erythema ab igne. Affected skin is characterized by reticular pink colored and hyperpigmented mottled patches. Patients may complain of associated pruritus, paresthesias, or may be asymptomatic. Treatment is limited and patients are instructed to avoid triggers.

Chronic moderate heat dermatitis, chronic radiant heat dermatitis, toasted skin syndrome, fire stains, hot-water bottle rash, laptop thigh.

• Rare disease.
• Women, in particular those who are overweight, are affected more often than men.

• The skin findings form as a result of multiple exposures to an intense source of heat.
• Erythema ab igne has been noted for many years, and the sources of heat have changed over time. It used to be reported in women who stay for long periods of time in front of open fires, fireplaces, or furnaces to cook.1-4 Most of the lesions were appearing on the medial side of the thigh and the lower leg in general.
• Currently, erythema ab igne is seen on different parts of the body, depending on what source of heat initiated the pathology, the angle of the heat radiation, the morphology of the skin, and the layers of clothing. Some of the modern-day examples are repeated application of hot-water bottles or heating pads to treat chronic pain, exposure to car heaters and furniture with internal heaters, the use of a laptop computer for long periods, and cooks and chefs who stand for long periods in the range of heat. Other causes include hot bricks, infrared lamps, and even microwave popcorn. Ultrasound physiotherapy was also reported as a cause of erythema ab igne. Recently, there was a reported case of frequent prolonged hot baths that caused the disease.5

• Persistent exposure to heat.
• Occupations that involve chronic exposure to external heat sources (e.g., kitchen workers, silversmiths, jewelers, foundry workers).6

Clinical Features

• Some patients have mild pruritus or burning sensation, but the majority of patients are asymptomatic.
• Skin lesions may not appear immediately after the exposure; it might take a period of 1 month to show up. Skin changes start as a reddish-brown pigmentation distributed as a mottled rash and are followed by skin atrophy (Figures 200-1, 200-2, and 200-3).
• Telangiectasias with diffuse hyperpigmentation and subepidermal bullae may also develop.
• The rash appears mesh-like or net-like in the area exposed to the heat. The heat can be from fireplaces, heating pads, laptop computers, open fires, place heaters, and hot-water bottles (Figures 200-1, 200-2, 200-3, 200-4, 200-5, 200-6, and 200-7).
• Malignant melanoma and various sarcomas are reported to arise in burn scars; however, those arising in areas of erythema ab igne have not been reported to date.

Typical Distribution

At the area of heat exposure, which is most often the legs or back (Figure 200-4).

Laboratory Studies

None recommended.

Skin Biopsy

• In almost all cases, the diagnosis is based on the history and physical exam. Once the typical skin pattern is seen by the clinician, a few questions often will prompt the patient to recall the heat source.
• In some rare cases, Markel cell carcinoma and squamous cell carcinomas have developed in areas of erythema ab igne.7-9
• If clinically warranted, a biopsy is performed to exclude the possibility of malignant transformation.
• Histopathology shows epidermal atrophy, subepidermal separation, and haziness of the dermoepidermal junction. Dilation of capillaries and connective tissue disintegration, elastosis, hemosiderin deposition, melanocytosis, and abundance of inflammatory cells are all seen in the dermis. Some of these lesions might progress to actinic keratosis, which could be a precursor for squamous cell carcinoma of the skin.

Erythema ab igne should be differentiated from other diseases with skin changes that mimic its presentation.

Livedo Reticularis

• Reticular cyanotic cutaneous discoloration surrounding pale central areas caused by dilation of capillary blood vessels and stagnation of blood (Figure 200-8).
• Occurs mostly on the legs, arms, and trunk and appears to be a purplish mottling of the skin.
• More pronounced in cold weather.
• Idiopathic condition that may be associated with systemic diseases such as systemic lupus erythematosus (SLE).

Poikiloderma Atrophicans Vasculare

• A variant of mycosis fungoides (cutaneous T-cell lymphoma) (see Chapter 176, Cutaneous T-Cell Lymphoma).
• Circumscribed violaceous erythema.
• Occurs mostly in posterior shoulders, back, buttocks, V-shaped area of anterior neck and chest.
• May be asymptomatic or mildly pruritic.
• May remain stable in size or gradually increase.
• Numerous atypical lymphocytes are observed around dermal blood vessels, and some epidermotropism is observed.

Cutis Marmorata

• Net-like reticulated pink patches seen early usually seen in premature newborns.
• Improves with rewarming of the skin, worsens with cooling.

Cutis Marmorata Telangiectasia Congenita

• Net-like reticulated pink patches.
• Persists despite rewarming.
• Genodermatosis usually associated with underlying limb atrophy.

Acanthosis Nigricans

• Velvety, light-brown-to-black markings usually on the neck, under the arms, or in the groin (see Chapter 220, Acanthosis Nigricans).
• Most often associated with being overweight.
• More common in people with darker skin pigmentation.
• A disorder that may begin at any age and that may be inherited as a primary condition or associated with various underlying syndromes.
• Should be able to distinguish from erythema ab igne by the typical location around the neck and in the axilla.

• The first goal of treatment is to identify the source of heat radiation to avoid further exposure. For mild lesions, no intervention is needed after the heat source is removed and the probability of full resolution is good.
• Topical retinoids, vitamin A derivatives, hydroquinone, and 5-fluorouracil have been prescribed to treat the abnormal skin pigmentation.10 Laser therapy has been used to even out the skin color.4,10 SOR C

Prognosis is excellent for full resolution if the external heat source is removed or discontinued. However, the hyperpigmentation may remain and various treatments may not succeed in returning the skin to its normal pigmentation.

Follow-up visits are recommended if there are new changes to the skin after removing the source of heat. This is to diagnose and manage any malignant transformation.

Patients should avoid excessive and prolonged localized heat exposures (i.e., fireplaces, heating pads, laptop computers, and hot-water bottle applications).

There are many ways to shield the thighs from the heat of a laptop computer, from the use of pillows and blankets to the purchase of special devices manufactured for this purpose.

Patient Resources

• Wikipedia. Erythema Ab Igne—http://en.wikipedia.org/wiki/Erythema_ab_igne.

Provider Resources

• Medscape. Erythema Ab Igne—http://emedicine.medscape.com/article/1087535.
• DermNet NZ. Erythema Ab Igne—http://dermnetnz.org/vascular/erythema-ab-igne.html.