Skin Reactions to Sunlight ICD-9: 692.70 ICD-10: L56.8
The term photosensitivity describes an abnormal response to sunlight. Cutaneous photosensitivity reactions require absorption of photon energy by molecules in the skin. Energy is either dispersed harmlessly or elicits chemical reactions that lead to clinical disease. Absorbing molecules can be (1) exogenous agents applied topically or systemically, (2) endogenous molecules either usually present in skin or produced by an abnormal metabolism, or (3) a combination of exogenous and endogenous molecules that acquire antigenic properties and thus elicit a photoradiation-driven immune reaction. Photosensitivity disorders occur only in body regions exposed to solar radiation(Fig. 10-1).
Acute photosensitivity; three types.
1. A sunburn-type response with skin changes simulating a normal sunburn such as in phototoxic reactions to drugs or phytophotodermatitis (PPD).
2. A rash response with macules, papules, or plaques, as in eczematous dermatitis. These are usually photoallergic in nature.
3. Urticarial responses are typical for solar urticaria; but urticarial lesions can also occur in erythropoietic porphyria.
Chronic photosensitivity: chronic repeated sun exposures over time result in polymorphic skin changes that have been termed dermatoheliosis (DHe), or photoaging. A classification of skin reactions to sunlight is shown in Table 10-1.
Figure 10-1. Variations in solar exposure on different body areas.
TABLE 10-1 SIMPLIFIED CLASSIFICATION OF SKIN REACTIONS TO SUNLIGHT
Basics of Clinical Photomedicine
The main culprit of solar radiation-induced skin pathology is the ultraviolet (UV) portion of the solar spectrum. Ultraviolet radiation (UVR) is divided into two principal types: UVB (290–320 nm), the “sunburn spectrum,” and UVA (320–400 nm) that is subdivided into UVA-1 (340–400 nm) and UVA-2 (320–340 nm). The unit of measurement of sunburn is the minimum erythema dose (MED), which is the minimum UV exposure that produces an erythema 24 h after a single exposure. UVB erythema develops in 6–24 h and fades within 72–120 h. UVA erythema develops in 4–16 h and fades within 48–120 h.
Variations in Sun Reactivity in Normal Persons: Fitzpatrick Skin Phototypes (Table 10-2). Sunburn is seen most frequently in individuals who have pale white or white skin and a limited capacity to develop inducible, melanin pigmentation (tanning) after exposure to UVR. Basic skin color is divided into white, brown, and black. Not all persons with white skin have the same capacity to develop tanning, and this fact is the principal basis for the classification of “white” persons into four skin phototypes (SPT). The SPT is based on the basic skin color and on a person’s own estimate of sunburning and tanning (Table 10-2).
TABLE 10-2 CLASSIFICATION OF FITZPATRICK’s SKIN PHOTOTYPES (SPT)
SPT I persons usually have pale white skin color, blond or red hair, and blue eyes; but, in fact, they may have dark brown hair and brown eyes. SPT I persons sunburn easily with short exposures and do not tan. SPT II persons sunburn easily but tan with difficulty, while SPT III persons may have some sunburn with short exposures but can develop marked tanning. SPT IV persons tan with ease and do not sunburn with short exposures. Persons with constitutive brown skin are termed SPT V and with black skin SPT VI. Note that sunburn depends on the amount of UVR energy absorbed. Thus, with excessive sun exposure, even SPT VI person can have a sunburn.
Acute Sun Damage (Sunburn) ICD-9: 692.71 ICD-10:L55
Sunburn is an acute, delayed, and transient inflammatory response of normal skin after exposure to UVR from sunlight or artificial sources.
By nature, it is a phototoxic reaction.
Sunburn is characterized by erythema (Fig. 10-2) and, if severe, by vesicles and bullae, edema, tenderness, and pain.
Sunburn depends on the amount of UVR energy delivered and the susceptibility of the individual (SPT). It will therefore occur more often around midday, with decreasing latitude, increasing altitude, and decreasing SPT. Thus, the “ideal” setting for a sunburn to occur would be an SPT I individual (highest susceptibility) on Mt. Kenya (high altitude, close to the equator) at noon (UVR is highest). Of course, sunburn can occur at any latitude, but the probability for it to occur decreases with increasing distance from the equator.
Molecules that absorb UVR for UVB sunburn erythema are not known, but damage to DNA may be the initiating event. The mediators that cause the erythema include histamine for both UVA and UVB. In UVB erythema, other mediators include TNF-α, serotonin, prostaglandins, nitric oxide, lysosomal enzymes, and kinins. TNF-α can be detected as early as 1 h after exposure.
Skin Symptoms. Onset depends on intensity of exposure. Pruritus may be severe even in mild sunburn; pain and tenderness occur with severe sunburn.
Constitutional Symptoms. Some SPT I and II persons develop headache and malaise even after short exposures. In severe sunburn, the patient is “toxic”—with fever, weakness, lassitude, and a rapid pulse rate.
Skin Lesions. Confluent bright erythema always confined to sun-exposed areas and thus sharply marginated at the border between exposed and covered skin (Fig. 10-2). Develops after 6 h and peaks after 24 h. Edema, vesicles, and even bullae; always uniform erythema and no “rash,” as occurs in most photoallergic reactions. As edema and erythema fade vesicles and blisters dry to crusts, which are then shed.
Distribution. Strictly confined to areas of exposure; sunburn can occur in areas covered with clothing, depending on the degree of UV transmission through clothing, the level of exposure, and the SPT of the person.
Mucous Membranes. Sunburn is frequent on the vermilion border of the lips and can occur on the tongue in mountain climbers who stick their tongue out panting.
Figure 10-2. Acute sunburn Painful, tender, bright erythema with mild edema of the upper back with sharp demarcation between the sun-exposed and sun-protected white areas.
Dermatopathology. “Sunburn” cells in the epidermis (apoptotic keratinocytes); exocytosis of lymphocytes, vacuolization of melanocytes, and Langerhans cells. Dermis: endothelial cell swelling of superficial blood vessels.
Diagnosis and Differential Diagnosis
History of UVR exposure and sites of reaction on exposed areas. Phototoxic erythema: history of medications that induce phototoxic erythema. SLE can cause a sunburn-type erythema. Erythropoietic protoporphyria (EPP) causes erythema, vesicles, edema, and purpura.
Course and Prognosis
Sunburn, unlike thermal burns, cannot be classified on the basis of depth, i.e., first-, second-, and third-degree because 3° burns after UVR do not occur—therefore, there is no scarring. A permanent reaction from severe UV burns is mottled depigmentation, probably related to the destruction of melanocytes, and eruptive solar lentigines (see Fig. 10-23).
Figure 10-3. Phototoxic drug-induced photosensitivity (A) Massive edema and erythema in the face of a 17-year-old girl who was treated with demethylchlortetracycline for acne. (B) Dusky erythema with blistering on the dorsa of both hands in a patient treated with piroxicam.
Prevention. SPT I or II should avoid sunbathing, especially between 11 AM and 2 PM. Clothing: UV-screening cloth garments. There are now many highly effective topical chemical filters (sunscreens) in lotion, gel, and cream formulations.
Topical. Cool wet dressings and topical glucocorticoids.
Systemic. Acetylsalicylic acid, indomethacin, and NSAIDs.
Severe Sunburn. Bed rest. If very severe, a “toxic” patient may require hospitalization for fluid replacement, prophylaxis of infection.
Drug-/Chemical-Induced Photosensitivity ICD-9: 692.79 ICD-10: L56.0
Interaction of UVR with a chemical or drug within the skin.
Two mechanisms: phototoxic reactions, which are photochemical reactions and photoallergic reactions, where a photoallergen is formed that initiates an immunologic response and manifests in skin as a type IV immunologic reaction.
The difference between phototoxic and photoallergic eruptions is that the former manifests like an irritant (toxic) contact dermatitis or sunburn and the latter like an allergic eczematous contact dermatitis (see Table 10-3).
TABLE 10-3 CHARACTERISTICS OF PHOTOTOXICITY AND PHOTOALLERGY
Phototoxic Drug-/Chemical-Induced Photosensitivity ICD-9: 692.79 ICD-10: L56.0
An adverse reaction of the skin that results from simultaneous exposure to certain drugs (via ingestion, injection, or topical application) and to UVR or visible light or chemicals that may be therapeutic, cosmetic, industrial, or agricultural.
Two types of reaction: (1) systemic phototoxic dermatitis, occurring in individuals systemically exposed to a photosensitizing agent (drug) and subsequent UVR, and (2) local phototoxic dermatitis, occurring in individuals topically exposed to the photosensitizing agent and subsequent UVR.
Both are exaggerated sunburn responses (erythema, edema, vesicles, and/or bullae).
Systemic phototoxic dermatitis occurs in all UVR-exposed sites; local phototoxic dermatitis only in the topical application sites.
Systemic Phototoxic Dermatitis
Occurs in everyone after ingestion of a sufficient dose of a photosensitizing drug and subsequent UVR.
Etiology and Pathogenesis
Toxic photoproducts such as free radicals or reactive oxygen species such as singlet oxygen. Principal sites of damage are nuclear DNA cell membranes (plasma, lysosomal, mitochondrial). The action spectrum is UVA. Drugs eliciting systemic phototoxic dermatitis are listed in Table 10-4. Some drugs causing phototoxic reactions can also elicit photoallergic reactions ¡see below).
TABLE 10-4 THE MOST COMMON SYSTEMIC PHOTOTOXIC AGENTS3
An “exaggerated sunburn” after solar or UVR exposure that normally would not elicit a sunburn in that particular individual. Occurs usually within hours after exposure, with some agents such as psoralens after 24 h, and peaking at 48 h. Skin symptoms: burning, stinging, and pruritus.
Skin Lesions. Early. The skin lesions are those of an “exaggerated sunburn.” Erythema, edema (Fig. 10-3A), and vesicle and bulla formation (Fig. 10-3B) confined to areas exposed to light. An eczematous reaction is not seen in phototoxic reactions.
Special Presentations: Pseudoporphyria. With some drugs there is little erythema but pronounced blistering and skin fragility with erosions (see Fig. 23-11) and, upon repeated exposures, healing with milia, particularly on the dorsa of hands and lower arms. Clinically indistinguishable from porphyria cutanea tarda (PCT) (see Fig. 10-12) except for the lack of facial hypertrichosis—hence the term pseudoporphyria (see Section 23),
Nails. Subungual hemorrhage and photoony-cholysis can occur with certain drugs (psoralens, demethylchlortetracycline, benoxaprofen).
Pigmentation. Marked brown epidermal melanin pigmentation may occur in the course. With certain drugs especially, chlorpromazine and amiodarone, a slate gray dermal melanin pigmentation develops (see Fig. 23-9),
Dermatopathology. Inflammation, “sunburn cells” (apoptotic keratinocytes) in the epidermis, epidermal necrobiosis, intraepidermal, and subepidermal vesiculation
Phototesting. Template test sites are exposed to increasing doses of UVA (phototoxic reactions are almost always due to UVA) while patient is on the drug. The UVA MED will be much lower than that for normal individuals of the same SPT. After drug has been eliminated from the skin, a repeat UVA phototest will reveal an increase in the UVA MED.
Diagnosis and Differential Diagnosis
History of exposure to drugs and morphologic changes in the skin characteristic of phototoxic drug eruptions. Differential diagnosis includes regular sunburn, phototoxic reactions due to excess of endogenous porphyrins, and photosensitivity due to other diseases, e.g., SLE.
Course and Prognosis
Phototoxic drug sensitivity seriously limits or excludes the use of important drugs: diuretics, antihypertensive agents, and drugs used in psychiatry. Phototoxic drug reactions disappear after cessation of drug.
As for sunburn.
Topical Phototoxic Dematitis ICD-9:692.79 ICD-10: L56.0
Inadvertent contact with or therapeutic application of a photosensitizer, followed by UVA irradiation (practically all topical photosensitizers have an action spectrum in the UVA range).
The most common topical phototoxic agents are Rose Bengal used for ophthalmologic examination, the dye fluorescein and furocoumarins that occur in plants (compositae spp and umbiliforme spp), vegetables and fruits (lime, lemon celery, parsley), in perfumes and cosmetics (oil of bergamot), and drugs used for topical photochemotherapy (psoralens). The most common route of contact is either therapeutic or occupational exposure.
Clinical presentation is like acute irritant contact dermatitis (see Section 2), with erythema, swelling, vesiculation, and blistering confined to the sites of contact with the phototoxic agent.
Symptoms are smarting, stinging, and burning rather than itching.
Healing usually results in pronounced pigmentation (see Fig. 10-6). The most common and thus important topical phototoxic dermatitis is PPD, which is described below.
Phytophotodermatitis (PPD) ICD-9: 692.72 ICD-10: L56.2
An inflammation of the skin caused by contact with certain plants during recreational or occupational exposure to sunlight (plant + light = dermatitis).
The inflammatory response is a phototoxic reaction to photosensitizing chemicals in several plant families.
Common types of PPD are due to exposure to limes, celery, and meadow grass.
Synonyms: Berloque dermatitis, lime dermatitis.
Epidemiology and Etiology
Common. Usually in spring and summer or all year in tropical climates.
Race. All skin colors; brown- and black-skinned persons may develop only marked spotty dark pigmentation without erythema or bullous lesions.
Occupation. Celery pickers, carrot processors, gardeners [exposed to carrot greens or to “gas plant” (Dictamnus albus)], and bartenders (lime juice) who are exposed to sun in outside bars. Nonoccupational: housewives and users of perfumes containing oil of bergamot; persons walking and children playing in meadows develop PPD on the legs; meadow grass contains agrimony
Etiology. Phototoxic reaction caused by photoactive furocoumarins (psoralens) contained in the plants.
The patient gives a history of exposure to certain plants (lime, lemon, wild parsley, celery, giant hogweed, parsnips, carrot greens, figs). Use of perfumes containing oil of bergamot (which contains bergapten, 5-methoxypsoralen) may develop streaks of pigmentation only in areas where the perfume was applied. This is called berloque dermatitis (French: berloque, “pendant”).
Skin Symptoms. Smarting, sensation of sunburn, pain, later pruritus.
Skin Lesions. Acute: erythema, edema, vesicles, and bullae (Fig. 10-4). Lesions may appear pseudopapular before vesicles are evident (Fig. 10-5). Often bizarre streaks and artificial patterns (Fig. 10-5). On the sites of contact, especially the arms, legs, and face. Residual hyperpigmentation in bizarre streaks (berloque dermatitis) (Fig. 10-6),
Figure 10-4. Phytophotodermatitis (plant + light): acute with blisters These bullae were the result of exposure to umbilliferae and the sun. This 50-year-old housewife was weeding her garden on a sunny day. Umbilliferae contain bergapten (5-methoxypsoralen), which is a potent topical phototoxic chemical.
Figure 10-5. Phytophotodermatitis In a 48-year-old man who was sunbathing in a meadow. Before vesicles and blisters arise erythematous lesions may appear raised, giving the false impression of being papular. Note streaky pattern.
Figure 10-6. Berloque dermatitis The patient had applied a fragrant bath oil to her shoulders and chest but showered only the front of her body before going into the sun. The bath oil contained oil of bergamot, and pigmentation is now noted where it trickled down from the shoulders to the buttocks. (Courtesy of Dr. Thomas Schwarz.)
Diagnosis and Differential Diagnosis
By recognition of pattern and careful history. Differential diagnosis is primarily acute irritant contact dermatitis, with streaky pattern. Poison ivy dermatitis (see Fig. 2-8), but this is eczematous.
May be an important occupational problem, as in celery pickers. The acute eruption has a short life and fades spontaneously but the pigmentation may last for many weeks.
Wet dressings may be indicated in the acute vesicular stage. Topical glucocorticoids.
Photoallergic Drug/Chemical-Induced Photosensitivity ICD-9: 692.72 ICD-10: L56.1
This results from interaction of a photoallergen and UVA radiation.
In sensitized individuals, exposure to a photoallergen and sunlight results in a pruritic eczematous eruption confined to exposed sites and clinically indistinguishable from allergic contact dermatitis.
In most patients, the eliciting drug/chemical has been applied topically, but systemic elicitation also occurs.
Age of Onset. More common in adults.
Race. All SPTs and colors.
Incidence. Photoallergic drug reactions occur much less frequently than do phototoxic drug reactions.
Etiology and Pathogenesis
Topically applied chemical/drug plus UVA radiation. The chemicals are disinfectants, antimicrobials, agents in sunscreens, perfumes in aftershaves, or whiteners (Table 10-5). The chemical agent present in the skin absorbs photons and forms a photoproduct; this then binds to a soluble or membrane-bound protein to form an antigen to which a type IV immune response is elicited. Photoallergy is elicited only in those who have been sensitized. It can also be induced by systemic administration of a drug and elicited by topical administration of the same drug, and vice versa. UVA is always required.
TABLE 10-5 TOPICAL PH0T0ALLERGENSa
Skin Lesions. Highly pruritic. Acute photoallergic reaction patterns are clinically indistinguishable from allergic contact dermatitis (Fig. 10-7): papular, vesicular, scaling, and crusted. Occasionally there can also be a lichenoid eruption similar to lichen planus. In chronic drug photoallergy, there is scaling, lichenification, and marked pruritus mimicking atopic dermatitis or, again, chronic allergic contact dermatitis (Fig. 10-7)
Figure 10-7. Photoallergic drug-induced photosensitivity This 60-year-old male shows an eczematous dermatitis in the face. He was taking trimethoprim-sulfamethoxazole. Note relative sparing of eyelids (protected by sunglasses), under the nose, and the area under the lower lip (shaded areas).
Distribution. Confined primarily to areas exposed to light (distribution pattern of photosensitivity), but there may be spreading onto adjacent nonexposed skin. Of diagnostic help is the fact that in the face the upper eyelids, the area under the nose, and a thin strip of skin between the lower lip and the chin are often spared (shaded areas) (Fig. 10-7).
Dermatopathology. Epidermal spongiosis with lymphocytic infiltration.
History of exposure to drug, the allergic contact dermatitis pattern of the eruption, and its confinement to sun-exposed sites. Diagnosis is verified by the photopatch test: Photoallergens are applied in duplicate to the skin and covered. After 24 h, one set of the duplicate test sites is exposed to UVA, while the other set remains covered; test sites are read for reactions after 48-96 h. An eczematous reaction in the irradiated site but not in the nonirradiated site confirms photoallergy to the particular agent tested.
Course and Prognosis
Photoallergic dermatitis can persist for months to years. This is known as chronic actinic dermatitis (formerly persistent light reaction) (Fig. 10-8). In chronic actinic dermatitis, the action spectrum usually broadens to involve also UVB, and the condition persists despite discontinuation of the causative photoallergen, with each new UV exposure aggravating the condition. Chronic eczema-like lichenified and extremely itchy confluent plaques result (Fig. 10-8), which lead to disfigurement and a distressing situation for the patient. As the condition is now independent of the original photoallergen and is aggravated by each new solar exposure, avoidance of photoallergen does not cure the disease.
Figure 10-8. Drug-induced photosensitivity: chronic actinic dermatitis (formerly persistent light eruption) Erythematous plaques confined to the face and neck, sparing the shoulders. This male has excruciating pruritus.
In severe cases, immunosuppression (azathioprine plus glucocorticoids or oral cyclosporine) is required.
Polymorphous Light Eruption (PMLE) ICD-9: 692.72 ICD-10: L56.4
PMLE is a term that describes a group of heterogeneous, idiopathic, acquired, acute recurrent eruptions characterized by delayed abnormal reactions to UVR.
Manifested by varied lesions, including erythematous macules, papules, plaques, and vesicles. However, in each patient, the eruption is consistently monomorphous.
By far the most frequent morphologic types are the papular and papulovesicular eruptions.
Incidence. Most common photodermatosis. Prevalence from 10% to 21%. Average age is 23 years, much more common in females. All races, but most common in SPT I, II, III. In American Indians (North and South America), there is a hereditary type of PMLE that is called actinic prurigo.
Possibly a delayed-type hypersensitivity reaction to an (auto-) antigen induced by UVR. The action spectrum is UVA and less commonly UVB or UVA and UVB. Since UVA is transmitted through window glass, PMLE can be precipitated while riding in a car.
Onset and Duration of Lesions. PMLE appears in spring or early summer. It occurs within hours of exposure and, once established, persists for 7–10 days. Symptoms are pruritus.
Skin Lesions. The papular (Fig. 10-9) and papulovesicular types are the most frequent. Far less common are plaques or urticarial plaques (Fig. 10-10). The lesions are pink to red. In the individual patient, lesions are quite monomorphous, i.e., either papular or papulovesicular or urticarial plaques. Recurrences follow the original pattern.
Distribution. The eruption often spares habitually exposed areas (face and neck) and appears most frequently on the forearms, V area of the neck, arms, and chest (Fig. 10-9). However, lesions may occur on the face (Fig. 10-10), if there has not been previous exposure to the sun.
Figure 10-9. Polymorphic light eruption Clusters of confluent, extremely pruritic papules on the exposed chest, occurred in an SPT IV man the day following the first sun exposure of the season. The eruption also involved the arms, but spared the face and dorsal hands.
Figure 10-10. Polymorphic light eruption Erythematous plaques in the face following first sun exposure of the season. The butterfly distribution is very similar to that of lupus erythematosus.
Dermatopathology. Edema of the epidermis, spongiosis, vesicle formation, and mild liquefaction degeneration of the basal layer with dense lymphocytic infiltrate in the dermis.
Immunofluorescence. Negative ANA.
Delayed onset of eruption, characteristic morphology, and the history of disappearance of the eruption in days. In plaque-type PMLE, a biopsy and immunofluorescence studies are mandatory to rule out LE (Fig. 10-10). Phototesting is done with both UVB and UVA. Test sites are exposed daily, starting with two MEDs of UVB and UVA, respectively, for 1 week to 10 days, using increments of the UV dose. In more than 50% of patients, a PMLE-like eruption will occur in the test sites.
Course and Prognosis
The course is chronic and recurrent. Although some patients may develop “tolerance” by the end of the summer, the eruption usually recurs the following spring and/or when the person travels to tropical areas in the winter. Spontaneous improvement or even cessation of eruptions occurs after years.
Prevention. Sunblocks are not always effective but should be tried first in every patient.
Systemic β-carotene, 60 mg three times a day for 2 weeks, before going in the sun. Oral prednisone 20 mg/day given 2 days before and 2 days during exposure is a good prophylaxis. Also, intramuscular triamcinolone acetonide, 40 mg, will suppress an eruption when administered a few days before a trip to a sunny region.
PUVA (Photochemotherapy) and narrowband UVB (311 nm) are very effective when given in early spring by inducing “tolerance” for the summer. Treatments have to be given before the sunny season, have to be repeated each spring, but are usually not necessary for more than 3 or 4 years.
Solar Urticaria ICD-9: 708.9 ICD-10: L56.3
Uncommon sunlight-induced whealing confined to exposed body sites.
Eruption occurs within minutes of exposure and resolves in a few hours. Very disabling and sometimes life threatening.
Action spectrum is UVB, UVA, and visible light or any combination thereof. Most commonly UVA (Fig. 10-11).
Solar urticaria is an immediate type I hypersensitivity response to cutaneous and/or circulating photoallergens.
Therapy: multiple phototherapy sessions in low but increasing doses on the same day (“rush hardening”); oral immunosuppressive agents or plasmapheresis.
Prevention: sun avoidance, sunscreens with high protection factors against action spectrum.
Figure 10-11. Solar urticaria, test sites Since wheals induced by sun exposure are transient and have usually disappeared when a patient comes to the clinic and can be photographed, we are showing test sites after diagnostic phototesting. The upper row of the template test sites was exposed to increasing doses of UVB and revealed only erythema (figures indicate mJ/cm2 applied). After 24 hours the template test sites in the lower row were exposed to 0.5 and 1 J/cm2 UVA (which are extremely low doses) and immediately after the exposure this picture was taken. Note massive urticarial reaction in the UVA-exposed test sites indicating UVA-induced solar urticaria.
Various wavelengths of UVR and/or visible light can elicit or aggravate a number of dermatoses.
In these cases, the eruption is invariably similar to that of the primary condition.
An abbreviated list is given below, but it should be emphasized that among these disorders SLE is by far the most important.
Acne, atopic eczema, carcinoid syndrome, cutaneous T cell lymphoma, Darier disease, dermatomyositis, disseminated superficial actinic porokeratosis, erythema multiforme, Hailey—Hailey disease, herpes labialis, keratosis follicularis (Darier disease) lichen planus, pellagra, pemphigus foliaceus (erythematosus), pityriasis rubra pilaris, psoriasis, reticulate erythematous mucinosis syndrome, rosacea, seborrheic dermatitis, lupus erythematosus, transient acantholytic dermatosis (Grover disease).
Metabolic Photosensitivity—the Porphyrias
For classification of the porphyrias, see Table 10-6. Acute intermittent porphyria (AIP) is not dealt with in detail here because it has no skin manifestations.
TABLE 10-6 CLASSIFICATION AND DIFFERENTIAL DIAGNOSIS OF PORPHYRIAS
Porphyria Cutanea Tarda ICD-9: 277.1 ICD-10: E80.1
PCT occurs mostly in adults.
Patients do not present with characteristic photosensitivity but with complaints of “fragile skin,” vesicles, and bullae, particularly on the dorsa of the hands, after minor trauma.
Purple-red suffusion of central facial skin, brown hypermelanosis, and hypertrichosis of the face.
Scleroderma-like changes and scars in exposed areas.
The diagnosis is confirmed by the presence of a pinkish-red fluorescence in the urine when examined with a Wood lamp.
PCT is distinct from variegate porphyria (VP) and AIP in that patients with PCT do not have acute life-threatening attacks.
Furthermore, the drugs that induce PCT are fewer than the drugs that induce VP and AIP.
Onset 30-50 years, rarely in children; females on oral contraceptives; males on estrogen therapy for prostate cancer. Equal in males and females.
Heredity. Most PCT patients have type I (acquired) induced by drugs or chemicals. Type II (hereditary), autosomal dominant; possibly these patients actually have VP, but this is not yet resolved. There is also a “dual” type with VP and PCT in the same family.
Etiology and Pathogenesis
PCT is caused by either an inherited or acquired deficiency of UROGEN decarboxylase. In type I (sporadic, acquired PCT-symptomatic), the enzyme is deficient only in the liver; in type II (PCT-hereditary), it is also deficient in red blood cells (RBCs) and fibroblasts. Chemicals and drugs that induce PCT: Ethanol, estrogen, hexachlorobenzene, chlorinated phenols, iron, and tetrachlorodibenzo-p-dioxin. High doses of chloroquine lead to clinical manifestations in “latent” cases (low doses are used as treatment). Other predisposing factors: Diabetes mellitus (25%), hepatitis C virus, and hemochromatosis.
Skin Lesions. Gradual onset. Patients present with fragility of skin on exposed sites. Tense bullae and erosions on normal-appearing skin (Fig. 10-12); slowly heal to form pink atrophic scars, milia (1–2 mm) on dorsa of hands and feet, nose, forehead, or (bald) scalp. Purplered suffusion (“heliotrope”) of central facial skin (Fig. 10-13A), especially periorbital areas. Brown hypermelanosis, diffuse, on exposed areas. Hypertrichosis of face (Fig. 10-14). Scleroderma-like changes, diffuse or circumscribed, waxy yellowish-white areas on exposed areas of face (Fig. 10-13B), neck, and trunk.
Figure 10-12. Porphyria cutanea tarda Bullae and atrophic depigmented scars on the dorsum of both hands. This is not an acute reaction to sun exposure but develops over time with repeated sun exposure and occurs after minor trauma. The patient presents with a history of “fragile” skin bullae and scars.
Figure 10-13. Porphyria cutanea tarda (A) Very subtle periorbital violaceous coloration. (B) Sclerodermoid thickening, scars, and erosions on the forehead.
Figure 10-14. Porphyria cutanea tarda Hypertrichosis in a woman who had been on a prolonged regimen with estrogens. Under Wood light her urine showed a bright coral-red fluorescence, as shown in Fig. 10-15.
Dermatopathology. Bullae, subepidermal with “festooned” (undulating) base. PAS staining reveals thickened vascular walls. Paucity of an inflammatory infiltrate.
Immunofluorescence. IgG and other immunoglobulins at the dermal-epidermal junction and in and around blood vessels, and in the sun-exposed areas of the skin.
Chemistry. Plasma iron and liver enzymes may be increased. High level of iron stores in the liver. The patient may have hemochromatosis. Blood glucose is increased in those patients with diabetes mellitus (25% of patients).
Porphyrin Studies in Stool and Urine (Table 10-6). Increased uroporphyrin (I isomer, 60%) in urine and plasma. Increased isocoproporphyrin (type III) and 7-carboxylporphyrin but not protoporphyrin in the feces. No increase in δ-aminolevulinic acid or porphobilinogen in the urine.
Simple Test. Wood lamp examination of the urine shows orange-red fluorescence (Fig. 10-15); to enhance, add a few drops of 10% hydrochloric acid.
Figure 10-15. Porphyria cutanea tarda: Wood light Coral-red fluorescence of the urine of a patient with PCT as compared to that of a normal control.
Liver Biopsy. Reveals porphyrin fluorescence and often fatty liver. May also show cirrhosis and hemochromatosis.
Diagnosis and Differential Diagnosis
By clinical features, pink-red fluorescence of urine and elevated urinary porphyrins. Bullae on dorsa of hands and feet can occur in pseudo-PCT (see Section 23) and in chronic renal failure with hemodialysis. Epidermolysis bullosa acquisita (see Section 6) has the same clinical picture (increased skin fragility, easy bruising, and light- and trauma-provoked bullae) but no hypertrichosis and hyperpigmentation.
1. Avoid ethanol, stop drugs that could induce PCT, and eliminate exposure to chemicals (chlorinated phenols, tetrachlorodibenzo-p-dioxin),
2. Phlebotomy is done by removing 500 mL of blood at weekly or biweekly intervals. Clinical and biochemical remission occurs within 5-12 months after regular phlebotomy. Relapse within a year is uncommon (5-10%).
3. Low-dose chloroquine is used to induce remission of PCT in patients in whom repeated phlebotomies cannot be done because of anemia. Since chloroquine can exacerbate the disease and, in higher doses, may even induce hepatic failure in these patients, this treatment requires considerable experience. However, long-lasting remissions and, in a portion of patients, clinical and biochemical “cure” can be achieved.
A serious autosomal-dominant disorder of heme biosynthesis. Protogen oxidase defect → accumulation of protoporphyrinogen in the liver → excretion in bile → nonenzymatically converted to protoporphyrin → high fecal protoporphyrin.
All races; common in white South Africans.
Accentuated by ingestion of drugs (Table 10-7) → precipitation of acute attacks of abdominal pain, nausea, vomiting, delirium, seizures, personality changes, coma, and bulbar paralysis.
Skin lesions identical to those of PCT [vesicles and bullae (Fig. 10-16), skin fragility, milia, and scarring of the dorsa of the hands and fingers]. Periorbital heliotrope hue, hyperpigmentation, and hypertrichosis in exposed areas. Lesions result from exposure to sunlight.
Increased excretion of porphyrins; characteristic are high levels of protoporphyrin in the feces (Table 10-6).
Differential diagnosis: other porphyrias (Table 10-6); pseudoporphyria, scleroderma, and acquired epidermolysis bullosa.
Treatment: none, oral β-carotene may prevent or ameliorate skin manifestations.
Lifetime disease; prognosis good if exacerbating factors are avoided. Rarely death can occur after ingestion of drugs that increase cytochrome P450.
Synonym: Porphyria variegata.
*In South Africa
TABLE 10-7 DRUGS HAZARDOUS TO PATIENTS WITH VARIEGATE AND ACUTE INTERMITTENT PORPHYRIA
Anesthetics: barbiturates and halothane
Anticonvulsants: hydantoins, carbamazepine, ethosuximide, methsuximide, phensuximide, primidone
Antimicrobial agents: chloramphenicol, griseofulvin, novobiocin, pyrazinamide, sulfonamides
Hormones: estrogens, progestin, oral contraceptive preparations
Minor tranquilizers: chlordiazepoxide, diazepam, oxazepam, flurazepam, meprobamate
Sulfonylureas: chlorpropamide, tolbutamide
Figure 10-16. Variegate porphyria Bullae on the dorsum of the foot and toes, a common site of sun exposure in patients wearing open footwear. This 42-year-old female was initially diagnosed with porphyria cutanea tarda. However, she gave a history of recurrent attacks of abdominal pain, which was a clue to the diagnosis of variegate porphyria; diagnosis was established by the detection of elevated stool protoporphyrins. Variegate porphyria (or South African porphyria) is akin to acute intermittent porphyria, in which there are no skin lesions but a fatal outcome may occur with ingestion of certain drugs (see Table 10-7). In South Africa, every white patient who is scheduled for major surgery must have laboratory tests for porphyrins since variegate porphyria is common in that country.
Erythropoietic Protoporphyria ICD-9: 277.1 ICD-10: F80.0
This hereditary metabolic disorder of porphyrin metabolism is unique among the porphyrias in that porphyrins or porphyrin precursors are usually not excreted in the urine.
Autosomal dominant, variable penetrance, defective enzyme is ferrochelatase.
Onset early childhood, late onset early adulthood.
Equal in females and males, all ethnic groups.
EPP is characterized by an acute sunburn-like photosensitivity, in contrast to the other common porphyrias (PCT or VP), where obvious acute photosensitivity is not a presenting complaint.
Symptoms occur rapidly within minutes of sun exposure and consist of stinging and burning.
Skin signs are erythema, edema, and purpura on face and dorsa of hands (Figs. 10-17 and 10-18).
Late (chronic) skin signs: shallow, often linear scars, waxy thickening and wrinkling of skin of face, and dorsa of hands (Fig. 10-19).
Increased protoporphyrin in RBCs, plasma, and stools (Table 10-6), and decreased ferrochelatase in bone marrow, liver, and skin fibroblasts.
Test for liver function indicated. Liver biopsy: portal and periportal fibrosis; brown pigment and birefringent granules in hepatocytes and Kupffer cells. Gallstones may be present, even in children; cirrhosis and liver failure may rarely occur.
Dermatopathology: eosinophilic homogenization and thickening of papillary blood vessels.
Diagnosis: clinical symptoms (there is no other photosensitivity disorder in which symptoms appear minutes after sun exposure), skin signs, and simple test: RBCs in a blood smear show transient red fluorescence at 400 nm.
Treatment none. Preventive management is β-carotene PO, which can prevent acute photosensitivity.
Synonym: Erythrohepatic protoporphyria.
Figure 10-17. Erythropoietic protoporphyria Diffuse erythematous swelling of the nose, forehead, and cheeks with petechial hemorrhage and telangiectasia. There are no porphyrins in the urine. A clue to the diagnosis is the history of tingling and burning within 4–5 min of sun exposure. The face of this woman appears yellow-orange because she was on β-carotene, which obviously did not protect her sufficiently.
Figure 10-18. Erythropoietic protoporphyria Massive petechial, confluent hemorrhage on the dorsa of the hands of a 16-year-old 24 h after exposure to the sun.
Figure 10-19. Erythropoietic protoporphyria, chronic skin changes Waxy thickening on the upper lip, cheeks, and nose makes the patient look older than he is (27 years). Note waxy thickening on the vermilion of lower lip, deep creases, and tiny shallow scars on the nose.
Dermatoheliosis (“Photoaging”) ICD-9: 692.74 ICD-10: L57.9
Repeated solar injuries over many years ultimately can result in the development of a skin syndrome, DHe. Very common.
It occurs in persons with SPT I-III and in persons with SPT IV who have had heavy cumulative exposure to sunlight, such as lifeguards and outdoor workers, over a lifetime. Most often in persons >40 years.
Action spectrum UVB but also UVA and possibly infrared.
Severity depends on the duration and intensity of sun exposure and on the indigenous (constitutive) skin color and the capacity to tan.
Note. If you want to demonstrate to an older patient the role of UVR in photoaging, just have him/her undress and compare the quality of his/her facial skin to that of the suprapubic skin.
Skin lesions: A combination of atrophy (of epidermis), hypertrophy (of papillary dermis due to elastosis), telangiectases, spotty depigmentation and hyperpigmentation, and spotty hyperkeratosis in light-exposed areas. Skin appears wrinkled, leathery, and “prematurely aged” (Fig. 10-20). Both fine, cigarette paper-like and deep furrow-like wrinkling; skin is waxy, papular with a yellowish hue, and both glistening and rough (Fig. 10-21). Telangiectasia and bruising (senile purpura) due to fragility of small vessels. Macular hyperpigmentations: solar lentigines (see below); macular hypopigmentations: guttate hypomelanosis, <3 mm in diameter, on the extremities. Comedones, particularly periorbital (termed Favre-Racouchot disease), particularly in cigarette smokers. Individuals with DHe invariably have actinic keratoses.
Distribution: exposed areas, particularly face, periorbital and perioral areas, and scalp (bald males). Nuchal area: cutis rhomboidalis (“red neck”) with rhomboidal furrows; lower arms, dorsa of hands.
Current management is to prevent skin cancers and the development of DHe with the use of protective sunblocks, a change of behavior in the sun, and the use of topical chemotherapy (tretinoin) that reverses some of the changes of DHe.
Figure 10-20. Dermatoheliosis Severe deep wrinkling. The skin appears waxy, papular with a yellowish hue (solar elastosis). This 68-year-old female mountain farmer lived at an altitude of 1000 m and had been working outdoors all her life. There is a basal cell carcinoma in the left zygomatic region.
Figure 10-21. Severe dermatoheliosis on the forearm of a 70-year-old female farmhand The skin is waxy, deeply wrinkled, and dry. Multiple solar keratoses have been removed from this arm by cryotherapy.
Solar Lentigo ICD-9: 709.090 ICD-10: L81.416
Solar lentigo is a circumscribed 1- to 3-cm brown macule resulting from a localized proliferation of melanocytes due to acute or chronic exposure to sunlight.
Onset usually >40 years.
Multiple lesions usually arise in sun-exposed sites. Most common in Caucasians (SPTs I to II).
Skin lesions strictly macular, 1–3 cm, and as large as 5 cm. Light yellow, light brown, or dark brown; variegated mix of brown (Fig. 10-22). Round, oval, with slightly irregular border, and ill defined. Scattered, discrete lesions, stellate, sharply defined, and roughly the same size after acute sunburn (Fig. 10-23) or overdosage of PUVA
Distribution. Exclusively exposed areas: forehead, cheeks, nose, dorsa of hands and forearms, upper back, chest, and shins.
Differential diagnosis: “Flat,” acquired, brown lesions on the exposed skin of the face, which may on cursory examination appear to be similar, have distinctive features: solar lentigo, freckles, seborrheic keratosis, spreading pigmented actinic keratosis (SPAK), and lentigo maligna (LM).
Cryosurgery or laser surgery is effective.
Figure 10-22. Dermatoheliosis: solar lentigines Multiple, very small to large (2 cm), variegated, tan-to-dark-brown macules on the cheek. Solar lentigines are not the same as ephelides (freckles)—they do not fade in the winter as freckles do. In contrast to the sharply marginated solar lentigines due to an acute sunburn that have roughly the same size shown in Fig. 10-23, the solar lentigines shown here are of different sizes and partially ill defined and confluent, which is characteristic of chronic cumulative solar damage. Note waxy thickening of skin and creases of dermatoheliosis.
Figure 10-23. Dermatoheliosis: solar lentigines Multiple stellate brown macules on the shoulder occurred after a sunburn. They are all of about the same size and sharply marginated, which is characteristic of sunburn-induced solar lentigines.
Chondrodermatitis Nodularis Helicis ICD-9: 380.0 ICD-10: H61.0
Usually occurs as a single elongated, exquisitely tender nodule, or a “beading” of the free border of helix of the ear. Common, perhaps due to constant mechanical trauma but most probably to UV radiation.
Appears spontaneously, enlarges quickly, measuring less than 1 cm (Fig. 10-24), firm, well-defined, round to oval with dome-shaped surface and sloping margins, white-waxy and translucent, and often ulcerated (Fig. 10-24).
More common in males than in females.
Spontaneous pain or tenderness. Can be intense and stabbing, paroxysmal, or continuous.
Differential diagnosis: basal cell carcinoma (BCC), actinic keratosis, in situ or invasive squamous cell carcinoma (SCC), hypertrophic solar keratosis, and keratoacanthoma. Also gouty tophus, rheumatoid and rheumatic nodules, and discoid lupus erythematosus.
Management includes intralesional injection of triamcinolone acetonide, carbon dioxide laser, and surgery. The definitive treatment is excisional surgery including the underlying cartilage.
Figure 10-24. Chondrodermatitis nodularis helicis An extremely painful nodule with central ulceration on the anthelix of a 60-year-old female. The central ulcer is covered with a crust and can be mistaken for a basal cell carcinoma.
Actinic Keratosis ICD-9: 702.0 ICD-10: L57.0
Single or multiple, discrete, dry, rough, adherent scaly lesions on the habitually sun-exposed skin of adults, usually on a background of DHe.
Actinic keratoses can progress to squamous cell carcinoma.
Synonym: Solar keratosis.
Age of Onset. Middle age, although in Australia and southwestern United States, solar keratoses may occur in persons <30 years.
Sex. More common in males.
Race. SPT I, II, and III; rare in SPT IV; almost never in people with black skin.
Occupation. Outdoor workers (especially farmers, ranchers, sailors) and outdoor sportspersons (tennis, golf, mountain climbing, deep-sea fishing).
Prolonged and repeated solar exposure in susceptible persons (SPT I, II, and III) leads to cumulative damage to keratinocytes by the action of UVR, principally, if not exclusively, UVB (290-320 nm).
Skin Symptoms. Lesions may be tender. Painful if excoriated with a fingernail.
Skin Lesions. Take months to years to develop. Adherent hyperkeratotic scale, which is removed with difficulty and pain (Figs. 10-25 and 10-26). Skin-colored, yellow-brown, or brown—“dirty” (Fig. 10-25); often there is a reddish tinge (Fig. 10-26). Rough, like coarse sandpaper, “better felt than seen” on palpation. Most commonly <1 cm, oval or round (Fig. 10-27).
Figure 10-25. Actinic keratoses Erythematous and brownish macules and papules with coarse, adherent scale become confluent on this bald scalp with dermatoheliosis. These hyperkeratoses are yellowish-gray. They are better felt than seen; gently abrading lesions with a fingernail usually induces pain, even in early subtle lesions, a helpful diagnostic finding.
Figure 10-26. Actinic keratoses, close up Grayish dirty-looking, tightly adherent scales on the forehead of an 80-year-old man. Abrading these hyperkeratoses is painful and leaves erosions. There is a small basal cell carcinoma at the border of the hairy scalp (arrow).
Figure 10-27. Actinic keratoses, higher magnification (A) A sharply defined yellow-brownish tightly adherent, rough hyperkeratosis with a reddish base. (B) This lesion is even more elevated and has a “stuck-on” appearance like a seborrheic keratosis. However, it is not greasy and soft but rather hard, rough, and painful when scraped.
Special Presentation. SPAK. This lesion is best described as “looks like lentigo maligna (LM) but feels like actinic keratosis” (Fig. 10-28). Uncommon. The distinctive features of SPAK include size (>1.5 cm), pigmentation (brown to black and variegated), and history of slow spreading, especially the verrucous surface. The lesion is important because it can mimic LM.
Figure 10-28. Spreading pigmented actinic keratosis (SPAK) “Looks like lentigo maligna” (see Fig. 12-7) but is rough and therefore “feels like actinic keratosis.” A nonpigmented actinic keratosis is seen in the preauricular region.
Distribution. Isolated single lesion or scattered discrete lesions. Face [forehead (Fig. 10-26), nose, cheeks), temples, vermilion border of lower lip], ears (in males), neck (sides), forearms, and hands (dorsa), shins, and the scalp in bald males (Fig. 10-25). Males with early pattern alopecia are especially prone to severe DHe and solar keratosis on the exposed scalp.
Dermatopathology. Large bright-staining keratinocytes, with mild-to-moderate pleomorphism in the basal layer extending into follicles, atypical (dyskeratotic) keratinocytes, and parakeratosis.
Diagnosis and Differential Diagnosis
Usually made on clinical findings. Differential: Chronic cutaneous lupus erythematosus; seborrheic keratosis, flat warts, SCC (in situ), superficial BCC. Highly hyperkeratotic lesions and SPAK may require biopsy to rule out SCC (in situ or invasive) or LM.
Course and Prognosis
Solar keratoses may disappear spontaneously, but in general remain for years. The actual incidence of SCC arising in preexisting solar keratoses is unknown but is estimated at 1%.
Prevention. Avoided by use of highly effective UVB/UVA sunscreens.
Topical Therapy. Cryosurgery
5-Fluorouracil (5-FU) Cream 5%. Effective, but difficult for many individuals. Treatment of facial lesions causes significant erythema and erosions, resulting in temporary cosmetic disfigurement. Efficacy can be increased if applied under occlusion and/or combined with topical tretinoin. This, however, leads to confluent erosions. Reepithelialization occurs after treatment is discontinued.
Imiquimod (twice weekly for 16 weeks). Causes cytokine dermatitis, also leads to irritation and erosions but is highly effective.
Topical Retinoids. Used chronically, is effective for prevention and treatment of DHe and superficial solar keratoses.
Diclofenac Gel. Used chronically, is effective in superficial acting keratoses; also irritating.
Facial Peels. Trichloroacetic acid (5-10%) effective for widespread lesions.
Laser Surgery. Erbium or carbon dioxide lasers. Usually effective for individual lesions. For extensive facial lesions, facial resurfacing is effective.
Photodynamic Therapy. Effective but painful and cumbersome.
Skin Reactions to Ionizing Radiation
Radiation Dermatitis ICD-9: 692.82 ICD-10: L58
Radiation dermatitis is defined as skin changes resulting from exposure to ionizing radiation.
Reversible effects are pain, erythema, epilation, suppression of sebaceous glands, and pigmentation (lasting for weeks to months to years).
Irreversible effects are atrophy, sclerosis, telangiectasias, ulceration, and radiation-induced cancers.
Type of Exposure
Result of therapy (for cancer, formerly also used for acne and psoriasis, and fungal infections of the scalp in children), accidental, or occupational (e.g., formerly, in dentists). The radiation causing radiodermatitis includes superficial and deep x-ray radiation, electron beam therapy, and grenz-ray therapy. It is a prevailing myth that grenz rays are “soft” and not carcinogenic; SCC can appear from >5000 cGy of grenz rays.
Types of Reactions
Acute. Temporary erythema that lasts 3 days and then persistent erythema, which reaches a peak in 2 weeks and is painful; pigmentation appears about day 20; a late erythema can also occur beginning on day 35-40, and this lasts 2-3 weeks. Massive reactions lead to blistering, erosions (Fig. 10-29), and ulceration, also painful; may occur as recall phenomenon. Permanent scarring may result.
Figure 10-29. Radiation dermatitis: acute, recall phenomenon This patient had breast cancer. She had a lumpectomy, methotrexate, and x-ray therapy and developed painful erythema and erosions at the irradiated site.
Chronic. After fractional but relatively intensive therapy with total doses of 3000–6000 rad, there develops an epidermolytic reaction in 3 weeks. This is repaired in 3–6 weeks, and scars and hypopigmentation develop; there is loss of all skin appendages and atrophy of the epidermis and dermis. During the next 2–5 years, the atrophy increases (Fig. 10-30); there is hyper- and hypopigmentation (poikiloderma), telangiectasia (Figs. 10-30 and 10-32) Necrosis and painful ulceration (Fig. 10-32) are rare but occur in accidental exposure or error in dose. Necrosis is leathery, yellow, and adherent and surrounding skin are extremely painful (Fig. 10-32). Ulcerations have a very poor tendency to heal and usually require surgical intervention. Lastly there may be radiation keratoses (Fig. 10-33A) and squamous cell carcinoma (Fig. 10-33).
Nails. Longitudinal striations (Fig. 10-33B) show thickening, dystrophy.
Figure 10-30. Radiation dermatitis: chronic There is sclerosis combined with atrophy and telangiectasia. This is the result of the irradiation of an infantile hemangioma in infancy.
Figure 10-31. Radiation dermatitis: chronic There is poikiloderma (brown: hyperpigmentation; white: hypopigmentation; red: telangiectasia) combined with atrophy and sclerosis. Hairs are absent. These massive skin changes are the result of overdosed irradiation the patient received as a child for fungal infection of the scalp. He is a candidate for SCC in the future.
Figure 10-32. Radiation dermatitis: chronic An area of severe poikiloderma with telangiectasias and irregular areas of necrosis that is leathery, yellowish-white, and tightly adherent. The lesion is extremely painful. Occurred after repeated electron beam radiations for mycosis fungoides.
Figure 10-33. Radiation-induced squamous cell carcinoma (A) These are the hands of an elderly radiologist who decades ago had disregarded precautionary measures and hardly wore gloves doing fluoroscopic work. There are multiple x-ray keratoses; the hyperkeratotic lesion on the right thumb has destroyed the nail and represents x-ray-induced SCC. (B) Nail changes in site of radiation exposure. Note the linear striations resulting from damage to the nail matrix. At the nailfold and extending proximally on the thumb, there is an irregular erythematous plaque that represents mostly SCC in situ but, focally, also invasive SCC.
Course, Prognosis, and Management
Chronic radiation dermatitis is permanent, progressive, and irreversible. SCC may develop in 4–40 years (Fig. 10-33A, B), with a median of 7–12 years. Tumors metastasize in about 25%; despite extensive surgery (excision, grafts, etc.), the prognosis is poor, and recurrences are common. BCC may also occur in chronic radiation dermatitis and appears mostly in patients formerly treated with x-rays for acne vulgaris and acne cystica or epilation (tinea capitis) (Fig. 10-31). The tumors may appear 40–50 years after exposure. Excision and grafting are often possible before the cancer develops.