Common skin diseases seen by the internist

COMMON SKIN DISEASES SEEN BY THE INTERNIST DAVID S. FEINGOLD, M.D. MADELINE BACHTA, M.D.

0011-5029/79/06001-39505.00 O 1979 Year Book Medical Publishers, Inc.

TABLE OF CONTENTS SELF-ASsESSMENT QUESTIONS THE ECZEMAS

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INFECTIONS AND INFESTATIONS OF THE SKIN . . . . . . .

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PSORIASIS

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ACNE

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SKIN L E S I O N S - - B E N I G N AND MALIGNANT .

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DRUG ERUPTIONS

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CUTANEOUS SIGNS OF SYSTEMIC DISEASES

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SELF-ASSESSMENT QUESTIONS The first three groups of questions consist of lettered headings followed by a list of numbered phrases. For each numbered phrase, select the one lettered heading t h a t is most closely related to it. I. A. Glucagonoma syndrome. B. Intraductal m a m m a r y carcinoma. C. Scurvy. D. Familial Mediterranean fever. E. Hypertriglyceridemia. 1. Eczematous lesion of nipple. 2. Acute eruption of grouped yellow-red papules on extensor surfaces, extremities and buttocks. 3. Acral and periorificial dermatitis. 4. Perifollicular hemorrhages and hemorrhagic gingivitis. 5. Erysipelas-like lesion. II. A. Psoriasis. B. Atopic dermatitis. C. Stasis dermatitis. D. Vesicular eruption of hands and feet. E. N u m m u l a r dermatitis. 1. Fungal infection and contact dermatitis must be excluded. 2. Coin-shaped patches of vesiculation, e r y t h e m a and scale. 3. Hereditary predisposition, increased epidermal turnover, plaques on extensor surfaces. 4. Hereditary predisposition, association with elevated IgE levels, flexural eczema. 5. Controlled best with support of venous return. III. A. Associated with S. p y o g e n e s only. B. Associated with S. a u r e u s only. C. Associated with both organisms. D. Associated with neither organism. 1. Impetigo.

2. Lymphangitis. 3. Furunculosis. 4. Erysipelas. 5. Erysipeloid. Which lettered word or phrase best answers the following 3 questions? IV. Melanoma should be suspected with lesions showing which of these characteristics? A. Variation in degree of pigmentation. B. A variety of colors. C. Spontaneous bleeding. D. Satellite lesions. E. All of the above. V. Which of the following treatments is contraindicated in acne therapy? A. Topical steroids. B. Benzoyl peroxide lotion. C. Tretinoin (trans-retinoic acid) D. Topical antibiotics. E. Systemic antibiotics. VI. Which of the following is the most frequent cause of drug eruption? A. Morphine. B. Packed red blood cells. C. Aminophylline. D. Digoxin. E. Aspirin. Answers are listed at the end of the article.

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is Chief of the Dermatology Section, Boston Veterans Administration Hospital, and Professor of Dermatology and Medicine, Boston University School of Medicine. He was chief of the infectious disease section at Beth Israel Hospital, Boston, before beginning his present career in dermatology. Dr. Feingold received his M.D. from Harvard Medical School and trained in internal medicine, infectious diseases and microbiology.

is Instructor of Dermatology at Boston University Medical School; Assistant in Dermatology at the Evans Memorial Department of Clinical Research and the Department of Dermatology, Boston University Medical Center; Consultant Dermatologist at the Boston Veterans Administration Hospital; and Consultant to the Gillette Corporation. She received her M.D. from Boston University School of Medicine and did her postgraduate studies at Cambridge Hospital and Boston University Medical Center. Dr. Bachta's interests have focused on contact and industrial dermatitis.

S K I N D I S E A S E S t h a t c a n be i m p r o v e d , o f t e n d r a m a t i c a l l y , b y t h e r a p y w i t h little or no u n d e s i r a b l e side effects afflict m o s t A m e r i c a n s a t s o m e time. P r o b l e m s affecting 1 - 8 % of t h e p o p u l a t i o n include one of the t y p e s of e c z e m a , f u n g a l infections, psoriasis, a c n e a n d s k i n t u m o r s . M a n y of t h e s e p r o b l e m s a n d t h e o t h e r s discussed in t h i s m o n o g r a p h c a n be

managed by a concerned general physician. It seems to us that too often physicians ignore dermatologic problems, refer patients immediately to dermatologists or embark reflexly on a trial of topical steroids. In this presentation we have attempted to: 1. Identify some of the most common skin problems with which patients present to physicians. 2. Outline diagnostic criteria and differential diagnoses of these conditions. 3. Discuss some of the simple diagnostic procedures that, after brief training in dermatology, physicians can perform before asking for specialty consultation. 4. Suggest rational therapy for the conditions. Several excellent textbooks of dermatology are available for reference. We have listed some of these in the References. The Manual of Dermatologic Therapeutics by Kenneth A. Arndt 1 deserves special mention, since it is designed as a work to help physicians with diagnosis and therapy of common skin problems. A review of the normal anatomy of the skin and the descriptive terminology of skin disease will facilitate reading the rest of this monograph. The epidermis is the most superficial layer of the skin, a constantly regenerating tissue several cell layers thick. The epidermis functions principally as a barrier, holding fluids and electrolytes in and keeping microorganisms out. The dermis supports the epidermis; it consists principally of collagen. Hair growth occurs in special hair-bearing epidermal structures called follicles, and most of the skin's oil-secreting glands (sebaceous glands) empty into these follicles and subsequently onto the skin surface. Sebum, the product of sebaceous gland secretion, has no attributable function on human skin. The ~'pilosebaceous apparatus" consists of a follicle and the attached sebaceous gland. Eccrine sweat glands are separate from the follicles and maintain thermal homeostasis. A macule is a flat spot or lesion, recognized therefore as a change in coloration. A papule is an elevation of the skin 5 mm or less in diameter. A plaque is a disk-shaped lesion. A vesicle is a blister 5 mm or less in diameter; a bulla is a blister greater than 5 mm in diameter. An erosion is a partial

loss of the e p i d e r m i s - f o r example, t h e a r e a u n d e r a rupt u r e d vesicle. The t e r m '~ulcer" implies a deeper process w i t h loss of d e r m a l tissue as well as epidermis. A p u s t u l e is a vesicle c o n t a i n i n g pus. Scales are d r y w h i t e flakes t h a t r e s u l t from visible s h e d d i n g of the m o s t superficial l a y e r of the epidermis, the h o r n y l a y e r or the s t r a t u m c o r n e u m . Collections of dried s e r u m or blood on t h e skin surface a r e r e f e r r e d to as crusts. A w h e a l (hive) is a red, e d e m a t o u s p l a q u e w i t h s h a r p l y defined, b u t s o m e t i m e s serpiginous, borders. '~Eczem a " or its s y n o n y m , d e r m a t i t i s , is a descriptive t e r m t h a t will be explained s u b s e q u e n t l y . Topical corticosteroids are t h e m o s t effective local antii n f l a m m a t o r y a g e n t s for several conditions. U n f o r t u n a t e l y , t h e y f r e q u e n t l y are used suboptimally. T h e y are simple to use in principle, b u t t h e m u l t i t u d e of p r o d u c t s a v a i l a b l e s o m e t i m e s creates confusion in t h e selection o f a specific t h e r a p y , and the v a r i a b l e s t h a t dictate t h e tactics of t r e a t m e n t often are not appreciated. T h e s e a g e n t s v a r y c o n s i d e r a b l y in potency, as c a n be seen in T a b l e 1. Some i n f l a m m a t o r y conditions are v e r y responTABLE 1.-SOME TOPICAL CORTICOSTEROID PREPARATIONS IN ORDER OF POTENCY* Most potent 1

4 5 Least potent 6

Fluocinonide cream, ointment, gel 0.05% (Lidex cream and ointment, Topsyn gel) Halcinonide cream, ointment 0.1% (Halog) Betamethasone dipropionate cream, ointment 0.05% (Diprosone) Betamethasone 17-valerate ointment 0.1% (Valisone) Triamcinolone acetonide cream 0.5% (Aristocort) Fluocinolone acetonide cream (HP) 0.2%, ointment 0.025% (Synalar) Triamcinolone acetonide ointment 0.1% (Aristocort; Kenalog) Betamethasone 17-valerate cream 0.1% (Valisone) Fluocinolone acetonide cream 0.025% (Synalar) Triamcinolone acetonide cream 0.1% (Kenalog) Desonide cream 0.05% (Tridesilon)

Preparations containing hydrocortisone *Modified from Arndt. ~

sive to the least potent agents. For example, seborrheic dermatitis usually responds to 1% hydrocortisone cream. Some other inflammatory conditions, such as vesicular dermatitis of the hands and/or feet, often respond only to the most potent topical corticosteroids. Since the side effects of a corticosteroid correlate with potency, the least potent agent that can control an eruption is advised, especially for chronic conditions. Continual use of these potent topical agents can lead to local side effects of folliculitis Csteroid acne"), telangiectasia and atrophy. These can occur with only a few weeks of treatment. When potent corticosteroids are used over extensive areas, especially with occlusive therapy (see below), adrenal suppression and/or cushingoid symptoms may occur. Hydration-of the skin prior t o use, such as soaking the part in water for a few minutes, can improve strikingly the efficacy of the steroid. Excellent and prolonged hydration occurs under occlusion with airtight, pliable plastic wraps such as Saran Wrap. Occlusion with topical steroids is indicated for m a n y recalcitrant inflammatory problems, but it must be weighed against the increased systemic absorption and local problems related to transient overgrowth of microorganisms, follicular plugging and inhibited heat exchange. Topical corticosteroids are available as lotions, creams, ointments and gels. Lotions and gels often are more acceptable when used on the scalp. Steroid ointments tend to have greater biologic activity than corticosteroids in creamy vehicles. However, ointments m a y be unacceptable to some patients because of their greasy feel. They m a y also create undesirable maceration in acute, weeping dermatitides. Occasionally tachyphylaxis is seen with the use of these agents. Discontinuation of the steroid for several days or occasionally changing preparations will restore efficacy.

THE ECZEMAS Eczema (dermatitis) is not a specific diagnosis but a microscopic and macroscopic pattern of reaction seen in a

number of clinically distinct inflammatory skin diseases. Eczema can result from many types of epidermal injury, either exogenous or endogenous. The prototype is contact dermatitis, such as poison ivy dermatitis. Acutely, the eruption is red, blistering, erosive a n d weeping. As healing evolves, the skin becomes dry, red and scaly. At this point, the skin m a y heal completely, but if persistent rubbing and scratching occur, lichenification m a y result. Lichenified skin is thickened (indurated), occasionally hyperpigmented and the skin markings are accentuated. In some patients, especially blacks, lichenification takes the form ofhyperpigmented aggregates of papules. Some common types of eczema and suggested therapies will be described. CONTACT DERMATITIS

Contact dermatitis m a y be either a delayed hypersensitivity reaction to a topically applied allergen or a reaction to an agent that directly damages skin tissue. In allergic contact dermatitis, the patients must have been exposed previously to allergens for a period of time; after a subsequent exposure, the sensitized lymphocytes initiate the eczematous reaction. Therefore, patients may develop contact dermatitis to agents they have used uneventfully in the past, at times for years. Irritant reactions occur when mild chemicals have frequent or prolonged contact with the skin (soaps, solvents) or when strong chemicals have brief contact (acids or alkalis). The former type of reaction is more common; frequently it occurs as an occupational problem. Contact dermatitis always must b e considered in the differential diagnosis of a localized eczematous eruption, and the localization often is a clue to the etiologic agent. The presence of linear lesions suggests that an external contactant, such as a plant allergen, is the problem. Facial dermatitis may be caused by soaps, cosmetics, hair sprays and dyes. Dermatitis of hands may be caused by soaps, detergents, solvents and a multitude of other chemicals used in the workshop or hobby shop. Dermatitis of the feet, especially the dorsa, m a y be caused by an allergy to chemicals used in processing shoe leather.

To effect cure, the specific allergen or irritant must be identified and removed. The reader is referred to Alexander Fisher's classic work C o n t a c t D e r m a t i t i s 4 for more detailed discussions of the patterns of distribution of contact dermatitis and the descriptions of the common and less common offending allergens, as well as cross reactions. If a suspected contact dermatitis is not resolved after 1 - 2 months by removal of the offending agent and symptomatic therapy, referral to a dermatologist is appropriate. Other diagnoses must be considered; atopic dermatitis, fungal infections and drug reactions sometimes m a y be eczematous. The dermatologist m a y also be more skilled in ferreting out the cause of contact dermatitis, and usually is prepared to do patch testing, which may be helpful in detecting an elusive allergen. ATOPIC DERMATITIS Some physicians consider eczema synonymouswith atopic dermatitis. However, atopic dermatitis has some specific features that distinguish it from other forms of eczematous dermatitis. The etiology and pathophysiology of atopic dermatitis remain a puzzle. In the adult it is an extremely pruritic, principally flexural eczema that occurs in families with an atopic diathesis (atopic dermatitis, asthma, hay fever or familial urticaria). The eruption frequently starts in infancy (around 3 months of age), usually as facial chapping, redness and occasionallyblistering. This often is the most acute stage of the disorder. Atopic babies may have more difficulty than others with diaper rashes. In early childhood, the rash is more often found in the flexural areas, although any part of the skin m a y be involved. Atopic dermatitis frequently remits at adolescence, but some afflicted individuals continue to have problems with dry, ~'sensitive" skin and, at times, dermatitis of the hands. Unfortunate individuals may have widespread atopic dermatitis that persists throughout adulthood; this form of adult atopic dermatitis frequently is called generalized neurodermatitis. Bacterial superinfection is a common complication. Other infectious complica10

tions of atopic dermatitis include generalized vaccinia and widespread cutaneous herpes simplex, both potentially lethal. SEBORRHEIC DERMATITIS This is a chronic intermittent condition that involves areas with active and large numbers of sebaceous glands; it is characterized by redness and fine scaling, especially of the scalp, eyebrows and nasolabial folds. Simple dandruff can present with similar scaling in the scalp but erythema is not present. In more extensive cases, involvement of the midchest, mid-back, axillae and groin may occur, and a resemblance to psoriasis becomes obvious. Hydrocortisone, 1% cream, or sulfur preparations (e.g., Sulfacet) and shampoos with sulfur and salicylic acid (e.g., Sebulex) or selenium sulfide (e.g., Selsun) usually control this eruption. VESICULAR DERMATITIS OF THE HANDS AND FEET Synonyms for this condition include pompholyx and dyshidrotic eczema. It is a chronic, recurrent, pruritic, vesicular ( in its acute stages) eruption of the palms and soles primarily. It frequently starts with vesicles on the lateral aspects of the fingers. Most often, it is idiopathic in nature. Fungal infections and contact dermatitis are among the commonly recognized causes of dermatitis of the hands and/or feet. Fungal infection must be ruled out by microscopic examination of the scales and culture. Contact dermatitis often is difficult to rule out, but the distribution, history and patch testing m a y be helpful. Unfortunately, this eczem a may be difficult to treat, especially when exposure to irritants continues. STASIS DERMATITIS

When valves in the perforating veins between the deep and superficial venous systems of the legs are incompetent, the high pressure of the deep veins is transmitted to the superficial veins. This results in edema, leakage of erythro11

cytes and an inflammatory process. The greatest degree of involvement, including ulceration, occurs medially over the location of the perforating veins. Ulceration frequently is complicated by cellulitis. Chronic stasis dermatitis results in hyper- and hypopigmentation as well as edema and dystrophic skin changes. In stasis dermatitis, the general therapies for eczema are of secondary importance. The dermatitis will lessen or even resolve if venous return is improved. This m a y be accomplished by elevation of the legs or with a semirigid dressing (Unna's paste boot). Elastic stockings made to measure for the individual patient can be very helpful. Unfortunately, patients inevitably complain about using the support stockings because they take considerable effort to put on (especially for a frail, elderly or obese patient) and they are hot and itchy in warm weather. However, once the patient makes the adjustment and regularly uses the support provided, stasis eczema often improves. MISCELLANEOUS ECZEMAS Nummular eczema is a common, chronic, intermittent eruption consisting of coin-shaped patches of erythema and small vesicles that evolve into discrete erythematous, crusting and scaly plaques. These plaques may measure up to several centimeters in diameter. Nummular eczema is said to be more frequent in individuals exposed to irritants (as in housewives, mechanics, etc.). During the course of atopic dermatitis, atopic patients m a y appear to have patches of nummular eczema, lending some support to the notion that n u m m u l a r dermatitis is a subtype of atopic dermatitis. Circumscribed neurodermatitis (lichen simplex chronicus) is a chronic pruritic disorder resulting from the t r a u m a of repeated rubbing and scratching. The lesions are lichenifled and occasionally psoriasiform in appearance. They often occur over bony prominences or on the back of the neck. The lesions occur in atopic patients frequently. At times, a discrete inciting stimulus such as an insect bite or trauma can be elicited. 12

COMPLICATIONS AND TREATMENT OF ECZEMATOUS DERMATITIS

The most common complication of any eczema is bacterial superinfection, characterized by copious exudate, purulent exudate, pustules or heavy serous crusting. Usually Staphylococcus aureus or Streptococcus pyogenes is the pathogen. Ideally, a culture should be taken. Initial therapy for suspected superinfection may be a penicillinase-resistant penicillin such as dicloxacillin. There is considerable debate as to whether topical antibiotics are effective in treating established skin infections. Given their doubtful efficacy, their tendency to macerate in ointment form and their potential for sensitization (especially neomycin), topical antibiotics should be considered second choices to the use of systemic agents. Topical corticosteroids are useful in hastening the involution of the eczema and probably do not aggravate the infectious component, as long as specific antibacterial therapy is given. The principles of treatment are the same for most forms of eczema. In the exudative phase, soaks should be applied for 1 5 - 20 minutes 3 - 6 times daily. The purpose of the soaks is to remove the crusts and exudate. For soaks, one m a y use tap water, isotonic salt solution, a l u m i n u m acetate (1 Domeboro tablet in a quart of water) or silver n i t r a t e (1 teaspoonful of 50% stock solution to 1 quart of water). After the soak, a light application of a corticosteroid cream should be applied. Soaks m a y be stopped when exudation stops and corticosteroid creams used until the eruption clears. Dry, chronic eczemas are best treated with a corticosteroid ointm e n t and greases such as hydrophilic petrolatum or Eucerin. The use of the ointment as a vehicle prevents evaporation of water from the epidermis and therefore reduces drying. Severe, acute, eczematous reactions m a y alternatively be treated with a brief course of systemic steroids (e.g., 40 mg prednisone daily, tapering to zero over a 2-week period). Intralesional corticosteroids (dermal injection at the site of the lesion are helpful in treating recalcitrant, localized processes. Antihistamines (e.g., chlorpheniramine maleate, 4 - 8 mg orally 4 - 6 times per day) should be offered to any eczema patient troubled with itching. 13

INFECTIONS AND INFESTATIONS OF THE SKIN

A variety of pathogenic microorganisms and parasites afflict the skin. Sometimes no treatment is required; however, acute disease and vexing chronic disease deserve therapy. BACTERIAL INFECTIONS (PYODERMAS) Bacterial infections of the skin (pyodermas) usually occur at sites of macroscopic or microscopic damage to the integrity of the epidermis. Group A beta-hemolytic streptococci (Streptococcus pyogenes) and/or Staphylococcus aureus are the usual offending agents. Impetigo, the most superficial infection, is characterized by oozing, crusting lesions with various degrees of erythema. Although S. aureus often is isolated in addition to S. pyogenes, the latter usually is the cause. Since glomerulonephritis complicates infection with nephritogenic streptococcal strains, therapy with benzathine penicillin or oral penicillin is indicated. Although topical antimicrobials and other local therapeutic measures often are recommended, convincing evidence of efficacy is lacking. S. pyogenes can cause rapidly spreading infections. The lymphatics are one conduit. Spread via the lymphatics (lymphangitis) can quickly result in bacteremia. Spread through the dermal lymphatics gives a characteristic clinical picture, erysipelas. These patients may be acutely ill. The characteristic morphologic picture is of a rapidly expanding, erythematous, raised, sharply defined plaque. Infection with S. pyogenes in the subcutaneous tissue (cellulitis) usually does not have the sharply defined periphery of erysipelas. Streptococcal cellulitis can be explosive, even mimicking infections caused by Clostridium perfringens, and requiring debridement, especially if myonecrosis occurs. Most streptococcal cellulitis and lymphatic infections will respond to aggressive antibiotic treatment with penicillins. Erythromycin, cephalosporins or clindamycin may be used in those individuals allergic to the penicillins. Whereas streptococcal infections tend to spread, staphylo14

coccal infections localize frequently as collections of pus. Most superficial is folliculitis, an infection usually in the bearded area. Abscesses or furuncles, often at areas of trauma, can be quite large, requiring drainage. Often drainage alone is adequate but, if lesions are multiple, penicillinaseresistant semisynthetic penicillins, cephalosporins or clindamycin are indicated in conjunction with drainage. Recurrent staphylococcal furunculosis can be a problem lasting a number of years. Rarely does the patient have a defect in his/her defenses against infections, such as polymorphonuclear leukocyte or immunoglobulin abnormalities. In the vast majority of cases the patient apparently is normal but harbors a virulent, opportunistic microorganism that is effective in causing furuncles, usually at the sites of minor trauma. Therapy for individual flare-ups is not difficult. Large furuncles must be drained and antistaphylococcal antimicrobial therapy usually will eradicate the active lesions. A program aimed at eliminating carriage of the staphylococci often is effective, using an antiseptic cleansing agent such as chlorhexidine and the application of bacitracin ointment to the nares twice daily. It is rather surprising that despite the frequency of staphylococcal skin infections, metastatic infection is rare. Usually the host is able to handle those organisms that m a y wander into the blood. When problems do occur, they usually are related to the presence of a locus minoris resistentiae such as an endocarditis-prone cardiac lesion. Rare but characteristic skin infections include anthrax, lupus vulgaris, erysipeloid, cutaneous diphtheria and atypical mycobacterial infections. In impaired hosts, unusual organisms can cause cutaneous infections. In hospitalized patients, gram-negative bacilli resistant to multiple antibiotics cause wound infections. Discussion of these infections is beyond the scope of this treatise, and, in fact, the vast majority of bacterial infections of the skin seen by the primary care physician are streptococcal and staphylococcal disease, which usually can be managed without a specialist.

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FUNGAL INFECTION There are more than 50,000 species of fungi. Only a few genera are pathogenic for man. One can classify medically important fungi into two broad groups based on the type of infection they cause: those restricted to the skin, such as the dermatophytic fungi and Malassezia furfur, and those that regularly cause deeper infections. Candida albicans may cause either superficial cutaneous or systemic infections. This discussion will be restricted to the organisms causing skin infections. Tinea versicolor (TV) is an infection caused by Malassezia furfur, a fungus that does not penetrate deeper than the horny layer and causes little inflammatory response. Five per cent of cutaneous fungal infections in the temperate zones are TV. Clinically, one observes either hypopigmented or brownish, scaling patches. Usually the infection is asymptomatic and only a cosmetic problem. As with other fungal infections of the skin, diagnosis can be made with certainty by finding hyphae and/or spores by microscopic examinations of scales treated with 10% aqueous K O H or Swartz-Medrik stain. This is a simple test to perform and one that requires no more equipment than most physicians have in t h e i r office. The presence of fungal elements on K O H examination is subtle and requires supervised practice for adequate recognition. Unfortunately, many scaling dermatoses are treated inappropriately because no KOH examination was done. Incidentally, the causative agent of TV will not grow on routine media for fungi. TV responds promptly to therapy with several agents, but griseofulvin, an oral antifungal agent (see below), is not effective. The topical antifungals we shall discuss later are effective but unnecessarily expensive for the often extensive lesions of TV. Selenium sulfide suspension (Selsun) applied for 15 minutes daily for 2 weeks o r 25% sodium thiosulfate (Tinver) applied twice daily for 2 weeks usually arrests the infection. The dermatophytic fungi are microorganisms growing only on skin, hair or nails. In the genera of clinically important dermatophytes (Trichophyton, Epidermophyton and 16

Microsporum) there are about 35 species that infect man. Although there is some specificity of certain organisms for anatomic areas, it is adequate for our purposes to l u m p them together and discuss dermatophytic infection based on the clinical type of infection. Tinea capitis, or ringworm of the scalp, no longer is the scourge of childhood it once was. When the diagnosis is made, griseofulvin therapy is effective. Tinea capitis can present as patchy hair loss either with no inflammation or with marked inflammatory swellings in response to certain fungi of animal origin. Diagnosis of some Microsporum species can be made by observing typical fluorescence of the hair under Wood's light (low-energy, long-wave ultraviolet light, i.e., UVA), by identifying the fungi microscopically in or on hair shafts or by fungal culture. Not all fungi that infect hair will fluoresce with Wood's light. Tinea corporis, or ringworm of nonhairy skin, is common, especially in humid, warm climates. When mature, the lesions often are multiple, annular and scaling, with advancing sharp margins and central healing. Tinea should be in the differential diagnosis of most scaling lesions. Errors in diagnosis can be avoided by the practice of compulsive examination of a K O H preparation on all scaling lesions suggestive of tinea corporis or of uncertain etiology. Tinea pedis is the most common fungal disease. More than half of the population is infected at one time or another. Usually the modest scaling or hyperkeratosis is insignificant. Subacute infection with blister formation m a y occur. Infections between the toe can result in maceration and a secondary, mixed bacterial infection. Of yet greater danger is spreading lymphangitis or cellulitis of the leg stemming from the damaged epidermal barrier caused by the fungal infection. Involvement of the nails (onychomycosis) is a problem of cosmetic concern to some patients. Tinea cruris (jock itch) is another common affliction. It usually is manifest as pruritic, sharply marginated, scaling brown or red patches. Lesions confused with tinea cruris are the superficial bacterial infection, erythrasma, a nonspecific '~irritant" dermatitis or C. albicans infection. C. albicans infections in the groin usually can be distin17

guished clinically from tinea cruris. The former usually are more inflammatory, presenting with scaling red macules and often with satellite papulopustular lesions. In males, scrotal involvement and balanitis may be present and, in females, vulvovaginitis. Other characteristic surface infections with C. albicans include paronychia, thrush and angular cheilitis (perleche). Dermatophytes can be identified with special culture media, e.g., Sabouraud's glucose agar, Mycosel or Dermatophyte Test Medium (DTM). Identification m a y take 2 - 3 weeks. C. albicans can be identified on media designed for bacterial culture, usually in 2 - 3 days. When treating fungal infections with dermatophytes and C. albicans, consider that warm, moist, occlusive conditions foster the infections and thus should be avoided. Several good topical antifungal agents are available and effective for lesions of limited extent. Tolnaftate (Tinactin) is effective against dermatophytes. Clotrimazole (Lotrimin), miconazole (Micatin) and haloprogin (Halotex) are effective for C. albicans as well as dermatophytes. Nystatin preparations are effective only against Candida. With more substantial or extensive dermatophytosis, griseofulvin often is i n d i c a t e d 500 mg griseofulvin microcrystalline orally once or twice daily with meals for 1 month. Candida infections are not sensitive to griseofulvin. Topical therapy for dermatophytic nail involvement usually is ineffective. Response of dermatophytic onychomycosis to griseofulvin is slow and the rate of relapse is high, thus it often is best to advise the patient to keep the involved nails filed short and to learn to live with fungal nails. The common macerated, interdigital, pedal lesions, although fungal in origin, frequently respond poorly to the antifungal agents, since mixed bacterial infection has supervened. Probably the most effective therapy for this condition is 20% aluminum chloride (Drysol) applied twice daily. It is drying and has a broad antimicrobial spectrum. It can be irritating and should not be used in the presence of acute inflammation. In summary, fungal infections usually are easy to diagnose and treat, once considered. Most can be handled ade18

quately by the primary care physician. The recalcitrant cases or situations in which the diagnosis is in question m i g h t best be referred to a dermatologist. VIRAL INFECTIONS The following discussion of viral skin diseases will be limited to warts, molluscum contagiosum and herpes simplex. Viral exanthems are beyond the scope of this monograph. Warts are intraepithelial skin tumors caused by the papilloma virus. Probably two-thirds of warts remit spontaneously within 2 years. The tumors can take on m a n y forms resulting in various degrees of discomfort based on location. Wart tissue itself is not intrinsically painful. The hyperkeratotic response to the wart virus on the bottom of the f o o t plantar w a r t - c a n cause intense pain on walking if the wart is located on a pressure site. Genital warts can be painful as well as disfiguring. Warts over pressure points can fissure, resulting in significant pain. Flat warts on the face, especially the bearded area of men, can number in the hundreds. Therapy will vary based on the location and the cosmetic result required. Although all of the wart virus must be destroyed to cure the lesion, destructive procedures should be very gentle on the plantar surface, since scar formation m a y cause symptoms as severe as the wart. Patients with plantar warts may be kept free from pain by frequent filing or paring of the hyperkeratotic tissue. Keratolytic agents such as 40% salicylic acid plasters or salicylic acid and lactic acid in flexible collodion (Duofilm) m a y be applied repeatedly to control and at times cure the lesions. Sharp dissection or curettage and electrodesiccation, although often effective in treating most warts, probably should not be used on plantar warts unless they are small and are not located on pressurebearing areas. Cantharidin, strong acids, liquid nitrogen and podophyllin are other modalities frequently used to t r e a t warts in different areas. Probably the internist's best approach to warts is to develop some facility with the use of the salicylic acid and lactic acid reagent in flexible collodion (Duofilm). Therapy with this agent often is effective. Fail19

ures or complicated problems then may be referred to a dermatologist. Molluscum contagiosum is another viral tumor of the skin caused by a poxvirus. The dome-shaped lesions vary from red, skin-colored to whitish with central umbilication. Although usually only a few millimeters in diameter, they can assume impressive proportions and numbers. Lesions are most common in children and frequently are clustered on the face or trunk. Genital molluscum can be bothersome, sexually transmitted lesions. The diagnosis can be confirmed by observing molluscum bodies from expressed core material stained with Wright's, Giemsa or Gram stain. Therapy is easier than for warts. A light freeze with liquid nitrogen, curettage and physical removal of the central core of keratinous material all often are adequate. Regression of the lesions usually is prompt and cosmetic results are excellent. Infections with herpes simplex virus, type 1 or 2, can recur frequently and be disabling. The lesions can occur anywhere but most commonly they are perioral (usually type 1) or on the genitals (usually type 2). Between the eruptions, the virus resides in the sensory root ganglia. Under various stimuli, the viruses propagate along the nerves and become vegetative, resulting in the characteristic vesicles grouped on an erythematous base. The clinical diagnosis can be confirmed by finding multinucleate giant cells in Wright- or Giemsa-stained scrapings from the vesicle bases. No known therapy will eliminate the virus from the ganglia. Although a multitude of topical treatments have been tried, none has been proved effective in controlled testing. Clinically, it seems that occlusive ointments prolong the period of active vesicles whereas drying agents shorten the period. Unfortunately, the best we can do now is to avoid doing harm and to watch for secondary bacterial infection. This is very little consolation for the patient with a monthly flare-up of herpes progenitalis.

20

INFESTATIONS

Scabies is a common mite infestation caused by Sarcoptes scabiei. The female burrows in the s t r a t u m corneum, laying eggs. The predominant symptom is nocturnal pruritus. Lesions occur primarily on the hands, in the intertriginous areas and on the glans penis. Characteristic burrows are diagnostic but are found rarely. E r y t h e m a t o u s nodules, excoriations and eczematous patches are more common. Secondary pyoderma also is seen commonly. Microscopic demonstration of the mite scraped from a lesion is diagnostic. G a m m a benzene hexachloride (Kwell) is a pesticide effective for t r e a t m e n t of scabies. It is applied as a cream or lotion to the total body from the neck down and left on for 24 hours. Usually the t r e a t m e n t is repeated in 1 week. All members of a household should be treated simultaneously. Clothing and linens should be washed in hot water or dry cleaned. Pediculosis is an infestation by the louse Phthirus pubis in the genital area and by Pediculosis capitis in the scalp. The organisms lay eggs on the hairs, visible as nits, and the adults may be found feeding on the skin surface. They and their products often are visible as brown-black dots. Extreme pruritus is characteristic. Fortunately, the diagnosis is not difficult if the condition is considered, and t h e r a p y with g a m m a benzene hexachloride shampoo is effective.

PSORIASIS Psoriasis is a chronic, hereditary, papulosquamous skin disease. The course is variable and m a y be complicated by arthritis. Psoriasis is seen in more t h a n 1% of the adult Caucasian population. The disease m a y be a minor cosmetic problem, but often the disease is a significant embarrassment for the patient and occasionally the ~heartbreak of psoriasis" is devastating. Psoriatic skin lesions present at any age, but usually in young adults. The lesions begin as erythematous, sharply marginated papules and scaling plaques with a characteristic silvery white scale. The elbows, knees, extensor surfaces of the extremities, the scalp, penis and lumbosacral region 21

often are affected first, but plaques can occur anywhere on the body, including the palms and soles. Usually the face is spared. Nail involvement is manifested by pitting of the nail plate, by onycholysis (separation of the nail from the nail bed), with yellowish discoloration and/or by subungual hyperkeratosis with thick, crumbly nail growth. Joint involvement, which often correlates with nail changes, can vary from arthralgias to multilating arthritis. Typically, the distal interphalangeal joints show sausage-shaped swellings. Alternatively, deformities suggestive of rheumatoid arthritis, such as ulnar digital deviation, but with negative serology are seen in psoriasis. Spondylitis with sacroiliac joint changes is another severe form of psoriatic arthritis. Less common but potentially dangerous forms of psoriasis include acral or generalized pustular psoriasis and exfoliative erythroderma. Hair changes are not seen and mucous membrane lesions, other t h a n penile lesions, are very uncommon. No other organ pathology has been reported, even with severe psoriasis. The diagnosis of psoriasis usually is not difficult. On occasion, other papulosquamous lesions such as localized eczematous processes (lichen simplex chronicus, seborrheic dermatitis), the skin lesions of Reiter's syndrome, drug reactions or plaques of mycosis fungoides m a y be confused with psoriasis. Histologically, psoriasis is characterized by marked epidermal hyperplasia with elongation of the dermal papillae. The clinical and histologic findings reflect a dramatically overactive synthetic activity in the epidermis. The usual epidermal turnover time of 28 days is decreased to less than 4 days in the involved skin. The cause of the defective control of epidermal synthesis remains elusive. The disease is more common in patients with histocompatibility antigens HLA-B17 and HLA-B13. In young people, especially those with HLA-B13 antigen, acute flare-ups of psoriasis often follow group A beta-hemolytic streptococcal infections and possibly other infectious processes. Emotional stress and skin t r a u m a (the Koebner phenomenon) also m a y precipitate new psoriatic lesions. Two theories of the pathogenesis of the disease are considered most likely. Histologically, the blood vessels of the 22

upper dermis in psoriasis show striking dilatation, which some believe is the primary pathologic change. Others contend that abnormal epidermal metabolism of the cyclic purine nucleotides, compounds known to regulate epidermal cell proliferation, is responsible for the epidermal hyperplasia. Definitive evidence showing which changes are primary rather than secondary has not yet been presented. Ideal therapy for psoriasis must await elucidation of the cause and the development of specific therapy to reverse the causal stimulus. Fortunately, one of the many modalities of therapy available usually can control even extensive disease at a level acceptable to the patient. Therapy aimed at eliminating the known precipitating agents such as stress and t r a u m a is in order. At times, sending the patient on vacation or admitting the patient to the hospital is surprisingly effective. Topical therapy with lubricants (e.g., petrolatum), keratolytic agents (e.g., salicylic acid), tars and/or corticosteroids often is effective. Lubricants give symptomatic relief. Keratolytic agents help remove thick scale. Tars have an antimitotic effect on epidermal synthetic activity. Unfortunately, crude coal tar, the most messy preparation, is more effective for many patients than are the purified, more cosmetically elegant tar derivatives. Topical corticosteroids are the mainstays of therapy. Most psoriatic plaques will regress on applications of potent corticosteroids twice daily. Resistant lesions often will yield if the corticosteroid is applied under thin plastic film such as Saran Wrap or Blenderm Tape. Primary care physicians should begin therapy of psoriasis with emollients and topical steroids. The occasional failure should be referred for dermatologic consultation either for more complicated combinations of topical therapy or for evaluation as a candidate for one or another of the therapeutic regimens discussed below. Ultraviolet light can be an effective addition to therapy. In the 1920s, Goeckerman at the Mayo Clinic devised a regimen consisting of daily applications of crude coal tar and daily irradiation with ultraviolet light in the 2 8 0 - 3 2 0 nm range, the sunburn spectrum or so-called UVB. Although 23

UVB probably does not provoke a phototoxic reaction to tar, as Goeckerman suggested, the benefit of this regimen has stood the test of time. Even the most difficult patients usually respond to 2 - 4 weeks of the Goeckerman regimen in the hospital or in a day-care center. There are many variations on the theme of tar and UVB. The major modification adds topical corticosteroids to the regimen. This results in a quicker response b u t there is concern that the remissions do not last as long when corticosteroids are used. Long-range ultraviolet light in the 3 2 0 - 4 0 0 nm range or so-called UVA has been used recently in the treatment of psoriasis as high-energy UVA lamps have become available. Used alone or in combination with tar, UVA has no advantage over UVB. However, when UVA has been used in conjunction with oral psoralens (phototoxic plant products with an action spectrum in the UVA range), dramatically beneficial effects on psoriasis have been observed. When used by experienced personnel, few side effects have been observed. However, since psoralens activated by UVA are powerful DNA cross-linking agents and, hence, potential carcinogens, the U. S. Food and Drug Administration is taking a cautious stance before approving this still experimental therapy for general use. Several antimetabolites topically and systemically have been tried for control of the epidermal hyperplasia in psoriasis. Methotrexate systemically is most effective. Doses of 7.5 - 30 mg orally or intramuscularly given in 3 divided doses over 24 hours once weekly are remarkably effective in controlling psoriasis. Chronic methotrexate therapy is hepatotoxic, but in the small intermittent doses used for psoriasis, liver damage is rare. It is suggested, however, that liver biopsy be performed before therapy is initiated and periodically while therapy is continued. Unfortunately, relapse on discontinuation of therapy is prompt, and usually one is committing the patient to long-term methotrexate. Hence, the initiation of methotrexate therapy should only follow careful evaluation and discussion of the benefits and risks. An added benefit of this antimetabolite is that it often is effective in stopping the progression of psoriatic arthritis; 24

and is the only such therapy available other than anti-inflammatory agents. In summary, with well-motivated patients, psoriasis usually can be controlled adequately with topical agents under the supervision of a primary care physician. The more difficult cases may be treated with more aggressive therapy involving UVB treatment, methotrexate or possibly psoralens and UVA. ACNE

Acne is characterized by comedones (blackheads and whiteheads) and inflammatory lesions (papules, pustules, nodules and cysts). The disease involves the areas with the greatest density of sebaceous glands, the face, chest and back; it begins with the escalation of sebum production in early puberty, increases in incidence through adolescence and can extend into the twenties or later. The amount of physical scarring secondary to intense inflammatory lesions and psychologic scarring caused by ache is impressive. Some of the mechanisms operative in acne have been defined. Comedones result from the plugging of pilosebaceous units with debris, which consists of horny follicular epidermal cells, sebum and its metabolites and bacteria. Sebum production often is increased in patients with acne, as frequently evidenced by large follicular openings and oily skin; it is likely that the sebaceous glands of patients with acne have greater than normal sensitivity to androgen stimulation. With obstruction of the pilosebaceous units there is an overgrowth of the normal cutaneous flora, especially the anaerobic P r o p i o n i b a c t e r i u m acnes. The inflammatory lesions result from rupture of the pilosebaceous follicle and the release of probably several inflammation-inciting substances into the dermis. These inflammatory stimuli or chemoattractants probably include the free fatty acids originating from the lipolytic activity of bacterial enzymes on triglycerides of sebum, other breakdown products of sebum and possibly the metabolic products of the proliferating P. genes.

25

T h e r a p y for a c n e is d i r e c t e d t o w a r d r e v e r s i n g o n e o r m o r e of the pathogenetic mechanisms. There are two important c o m e d o l y t i c a g e n t s to t r e a t follicular p l u g g i n g . B e n z o y l peroxide a n d t r e t i n o i n ( t r a n s - r e t i n o i c acid, R e t i n A) a r e b o t h irritants causing increased epidermal turnover. They cause p e e l i n g , e j e c t i o n o f c o m e d o n e s a n d p r e v e n t i o n of n e w c o m e do f o r m a t i o n . T r e t i n o i n is e s p e c i a l l y effective as a c o m e d o l y tic; it a p p e a r s to d e c r e a s e t h e a d h e s i v e n e s s o f t h e h o r n y foll i c u l a r e p i d e r m a l cell. B e n z o y l p e r o x i d e , i n a d d i t i o n t o its c o m e d o l y t i c a c t i o n , is q u i t e effective i n r e d u c i n g t h e d e n s i t y o f P . acnes. Its a n t i b a c t e r i a l a c t i o n p r e s u m a b l y is r e l a t e d to 9its o x i d i z i n g c a p a c i t y . A n t i b i o t i c s c a n also m a r k e d l y d e c r e a s e P. a c n e s in t h e pil o s e b a c e o u s follicles. T h u s , t h e i n f l a m m a t o r y s t i m u l i directly or i n d i r e c t l y r e l a t e d to t h e o r g a n i s m s a r e a b o l i s h e d or r e d u c e d . V a r i o u s r e g i m e n s for a n t i b i o t i c t h e r a p y a r e listed TABLE 2.-ACNE THERAPY-GUIDELINES Lesions consisting mostly of comedones

1. Tretinoin cream 0.05% every other day for 2 weeks. If there is no undue inflammation, increase to daily application. If the patient tolerates the therapy well but additional improvement is desired, 0.1% cream or solution may be used or 2. Benzoyl peroxide alcoholic gel, 5% or 10% daily or twice daily according to tolerance Lesions that include inflammatory papules and pustules

1. Any of above topical therapies, alone or in combination with antibiotics 2. Typical antibiotic regimens for acne: a. Tetracycline 500 mg twice daily, decreasing to the minimum required for the maintenance of response b. Erythromycin 250 mg twice daily c. Clindamycin 1% or 2% alcoholic solution twice daily, topically d. Tetracycline lotion (Topicycline) twice daily, topically 3. For women: estrogen-dominant oral contraceptives, e.g., Enovid-E Lesions that are severely inflammatory with nodules and cysts

1. Combination topical and antibiotic therapy, possibly with addition of the following: 2. Intralesional steroid therapy, e.g., injection of 0.05-0.2 ml triamcinolone acetanide (5 mg/ml) into the inflammatory lesion 3. Oral prednisone (30 mg/day) or dapsone is used occasionally in patients with recalcitrant, disfiguring or tender acne, or acne with systemic symptoms. They are best prescribed by a dermatologist 26

in Table 2. Decreasing sebum production is also effective therapy. In women, this can be accomplished with estrogen therapy. Inflammatory lesions can be reduced by intralesional injections of corticosteroids. Washing, scrubs and special diets probably are not substantively effective therapeutic maneuvers. When should an endocrine disorder be suspected in acne? In women who have acne and menstrual disorders or hirsutism, endocrine investigation should be considered, especially if the symptoms are progressive. Patients with severe acne resistant to usual therapy (comedolytics and antibiotics) probably should have an endocrine work-up as well. Recently, studies with sophisticated laboratory techniques suggest that many female patients with acne and normal menses m a y have somewhat elevated testosterone levels; this finding does not alter the m a n a g e m e n t of acne, except possibly to make one consider estrogen therapy sooner. Systemic agents such as iodides, corticosteroids and androgens cause an acneiform eruption, folliculitis. Isonicotinic acid hydrazide (INH), Dilantin and lithium have also been implicated. Oils and greases, topical corticosteroids, chronic t r a u m a or pressure and, at times, sunlight may induce folliculitis.

DRUG ERUPTIONS Reactions to drugs often have skin manifestations. These reactions can be of several types: (1) extension or exaggeration of the therapeutic effect of the drug, such as petechiae in patients using anticoagulants; (2) direct toxicity of the drug to the skin, such as striae in patients on corticosteroids; (3) phototoxic eruptions in areas exposed to the sun caused by light-induced formation of toxic products from agents such as tetracyclines or thiazides; and (4) hypersensitivity reactions to the drug or its metabolites. This discussion will be limited to these cutaneous hypersensitivity reactions. Immediate and accelerated allergic reactions consist of anaphylaxis, pruritus and urticaria caused by the release of histamine and other mediators from mast cells. Less well 27

understood are the much more common exanthematous or morbilliform eruptions. Typically, they are bright red, or ~drug" red, resemble viral exanthems and, at the most severe end of their spectrum, present as exfoliative erythroderma. Also seen uncommonly as cutaneous reactions to medicaments are acneiform eruptions, vesiculobullous eruptions, e r y t h e m a multiforme and vasculitis. Unfortunately, the morphology of the rash rarely helps define the inciting agent. Cutaneous hypersensitivity reactions to medications m a y appear several days to several years after medications have been instituted with an antigen to which the patient has not been exposed previously; an induction period of approximately 10 days of drug administration is required before hypersensitivity reactions occur. If induction of hypersensitivity has occurred in the past, a single dose of medication can trigger the cutaneous eruption within 24 hours. For example, an individual who has had several courses of penicillin for infections in the past may develop hives within several hours after re-exposure to penicillin. Frequently the nature of previous sensitization is obscure. A patient with a penicillin eruption appearing soon after treatment and without a history of prior treatment with penicillin m a y have been sensitized by environmental penicillin, such as the traces of penicillin that m a y be found in milk. A patient with a reaction to aminophylline on first usage may be allergic to the ethylenediamine component that he/she was exposed to when using Mycolog Cream (active ingredients include nystatin, neomycin sulfate, gramicidin and triamcinolone). The hypersensitivity to drug A, which a patient has never seen, may be from a cross sensitization to drug B. For example, sulfonamides can sensitize patients to sulfonylureas or thiazide diuretics. In cases of patients with drug rashes who are receiving several drugs, statistics provide a guide to which agents most likely are the cause. Some recent statistics on incidence are presented in Table 3. Disappearance of the rash within 2 days to 2 weeks after withdrawal of the drug supports the clinical diagnosis. Provocation of the rash by read28

TABLE 3.-DRUGS WITH REACTION RATES > 1%* DRUG

Trimethoprim-sulfamethoxazole Ampicillin Semisynthetic penicillins Whole blood Corticotropin Blood platelets Erythromycin Sulfisoxazole Penicillin G Gentamicin sulfate Cephalosporins Quinidine Plasma protein fraction *Modified from Arndt. 1

REACTION RATE (REACTIONS/1000 RECIPIENTS)

59 52 36 35 28 28 23 17 16 16 13 12 12

m i n is tr atio n of the dr ug is the most reliable diagnostic test. Provocation tests usually produce t he same reaction t h a t occurred initially. For example, if t he initial drug reaction was a morbilliform rash, a morbilliform rash is expected on readministration, not anaphylaxis. However, most physicians are r e l u c t a n t to do provocation testing, not only because of th e patient's discomfort but also for fear of provoking a more dangerous reaction. A pa r t from provocation testing t h e r e are no practical and reliable ways of supporting objectively the clinical diagnosis of dr ug eruption. Eosinophilia is not consistently present and is nonspecific. Skin biopsy is nonspecific, although increased n u m b e r s of tissue eosinophils suggest an allergic reaction. With penicillin, a special type of provocative test has been helpful. T he occurrence of a wheal-and-flare reaction on skin testing with penicilloyl polylysine and aqueous penicillin G m arks the group of patients who m a y develop immediate or accelerated reactions to penicillin. It is clear in the case of penicillin t h a t drug metabolites, breakdown products or c o n t a m i n a n t s are the cause of penicillin allergy. With most other drugs, the exact allergen has not been defined and such tests are not 29

possible. Another complexity compounding the diagnosis or prediction of drug allergies is the multiplicity of mechanisms involved. Types I, II, III and IV hypersensitivity reactions and combinations thereof have been demonstrated to be operative in cases of drug allergy. Treatment of drug rashes starts with withdrawal of the suspected offending agent. Use of epinephrine, systemic steroids, antihistamines and supportive measures depends on the type and severity of the reaction and the degree of the patient's discomfort. Epinephrine is the treatment of choice for the dangerous immediate or accelerated reactions. Systemic steroids often are very helpful in suppressing or aborting the distressing signs and symptoms of drug eruptions. Antihistamines may be helpful as a sedative or in blocking the mediator of the pruritus and vascular leakage. Topical antipruritic therapy is also an important aspect of therapy for many patients, e.g., baths, cool compresses and lotions or lubricants with 1/4% menthol and 1% phenol. If a suspected drug rash is not clearing within a week of drug withdrawal, the diagnosis must be reconsidered. One can never feel great confidence in a diagnosis made by exclusion, as frequently is the case with drug eruptions.

SKIN LESIONS-BENIGN AND MALIGNANT Everyone develops skin blemishes or lumps sooner or later. For cosmetic reasons and for fear of cancer, many patients consult their physicians for an evaluation. The common types of m a r k s and bumps presenting include those listed in Table 4. It is convenient to divide the lesions into those arising from certain specific cell types. This discussion will be aimed at trying to define those common lesions that should be treated by reassuring the patient and those that should be biopsied or referred to a dermatologist or surgeon for therapy. Unfortunately, there is no w a y to describe adequately these lesions so that an inexperienced physician will recognize them with confidence; only experience and clinical pathologic correlation will provide that. 30

TABLE 4.-SKIN LESIONS Lesions of the Keratinocyte

Seborrheic keratosis Actinic keratosis Bowen's disease Squamous cell carcinoma Basal cell carcinoma Lesions of the Melanocyte

Freckle Lentigo Nevus Malignant melanoma Vascular Lesions

Spider telangiectasis Senile hemangioma Venous lake Infectious Lesions

Verruca vulgaris Molluscum contagiosum Miscellaneous Lesions

Dermatofibroma Acrochordon Inclusion cyst LESIONS OF THE KERATINOCYTE Among the tumors of keratinocyte origin, seborrheic keratoses are the most common. They are benign intraepidermal overgrowths of basal cells and squamous cells with a b u n d a n t hyperkeratosis. Frequently they present a waxy, papillomatous surface. They have a '~stuck on" appearance and vary in color from flesh-colored to deeply pigmented. They usually are easily removed by curettage and often will fall off after a light freeze with liquid nitrogen. At times, lesions with stippled pigmentation can resemble pigmented basal cell epitheliomas (BCE). When the physician is not sure of the diagnosis, the former therapy is preferable, for microscopic examination of the specimen is possible. Seborrheic keratoses increase in number with age. Usually they can be correctly identified morphologically, and removal yields good cosmetic results. Rarely, one observes the rapid onset of a very large number of these keratoses, which itch, 31

the sign of Leser-Trelat; it is said that this m a y be one of the cutaneous signs of underlying malignancy. Other common keratinocytic lesions are malignant or have malignant potential. Actinic keratoses, or solar keratoses, are found in areas exposed to the sun, usually in fairskinned individuals. They are erythematous, scaling, often hyperkeratotic lesions, usually multiple. Only rarely do actinic keratoses progress to obvious squamous cell carcinoma (SCC); however, it m a y be impossible to distinguish actinic keratosis from early SCC morphologically. Individual actinic keratoses regress with minimal freezing by liquid nitrogen. Numerous lesions in an area are best treated with a course of topical 5-fluorouracil (5-FU). Lesions not responsive to 5-FU usually deserve biopsy. Since 5-FU causes an inflammatory, erosive dermatitis, often it is used best in combination with topical corticosteroids. Therapy with 5F U probably is guided best by someone experienced with the agent. Bowen's disease is a type of intraepidermal SCC. Lesions that have penetrated the basement membrane are obvious SCC. They both originate from keratinocytes that remain capable of differentiation. Hence, they often are scaling, hyperkeratotic lesions also. They must be destroyed. The preferred method depends on the location, size and depth of the lesions. Cryosurgery, curettage and electrodesiccation, surgical removal and radiotherapy are possibilities. It is beyond the scope of this work to spell out the indications and contraindications for each method. For certain lesions, one of the methods may be distinctly preferable because of the cure rates and/or cosmetic results. Solar radiation-induced SCCs rarely metastasize. However, lesions occurring at sites of chronic irritation, e.g., chronic infection, or on mucous membranes such as the lips are much more aggressive. BCE is the most common cancer, occurring primarily in areas exposed to the sun. Lesions metastasize very rarely but may be locally destructive. The cell type of origin shows little differentiation. However, the morphology of BCEs can vary greatly. One can see nodular, ulcerative, pigmented or morphea-like lesions. Typically, the lesions are telangiectatic nodules with pearly-appearing borders. BCEs must be 32

differentiated from dermal nevi and sebaceous gland hyperplasia, lesions t h a t m a y be treated more conservatively. The therapeutic principles discussed in relation to SCC are also applicable here. It is important to remember t h a t patients having had one BCE or SCC should be examined carefully at regular intervals to detect new lesions when they are small and more easily treated. LESIONS OF THE MELANOCYTE Pigmented or melanocytic lesions are most frightening to patients and physicians because of the well-publicized aggressive n a t u r e of m a l i g n a n t melanoma. The vast majority of brown spots are benign. Freckles are loci of increased sunstimulated melanin synthesis. The only remedy to reduce freckling in those susceptible to their development is to reduce exposure to the sun. This is a wise approach, since those most susceptible to freckling often are also most susceptible to solar damage to the skin (premature wrinkling, actinic keratoses, BCE and SCC). Lentigines (liver spots) are flat, brownish lesions t h a t increase with age, occur anywhere on the body and reflect a local increase in the number of normal melanocytes at the basal layer of the epidermis. Since melanocytes are more susceptible to cold damage t h a n are keratinocytes, treatment with liquid nitrogen can blanch a lentigo when this is desired for cosmetic reasons. The term nevus, as most commonly used, refers to a benign overgrowth of cells of melanocytic origin. The nests of melanocytes m a y be in the epidermis, in the dermis or at the junction of the two. When these cells proliferate in the dermis they m a y make no pigment. Thus, dermal nevi m a y present as colorless, dome-shaped lesions t h a t m a y be removed for cosmetic reasons by a simple shave excision. If melanin production does occur in the dermis, the lesion often has a bluish cast r a t h e r t h a n appearing brown due to the way light is scattered as it passes through tissue. Epidermal or junctional nevi usually are brown, regular and, at times, palpable. Nevi are very common. Which ones should be removed or 33

biopsied? Some guidelines have been developed based on the common morphologic characteristics of malignant melanoma. Lesions with variations in color, especially blue, red or white are suspect. Irregular lesions, especially those with nodular growth, should be biopsied. Lesions showing perceptible new growth are also suspect. Having defined these guidelines, it must be said that m a n y dermatologists will remove or biopsy most nevi that a patient questions as significant, since, unfortunately, even the most innocent-appearing lesion can be an early melanoma. Melanomas are more common in areas exposed to the sun, but they m a y occur anywhere that melanocytes occur. One cannot overemphasize the importance of doing a complete skin examination. The t r e a t m e n t for malignant melanoma is wide surgical excision. The question of lymph node dissection, immunotherapy or" chemotherapy depends on the location and the histology of the lesion. Detailed discussion of the criteria is beyond the scope of this presentation. VASCULAR LESIONS

Vascular lesions occurring in adulthood include spider and senile (cherry) angiomas. Both lesions occur more frequently on the upper half of the body. Spider angiomas are seen with changing estrogen metabolism, such as in liver disease, pregnancy or from birth control pills. At times, spider angiomas can be eradicated by electrocoagulation of the central arteriole, which feeds the superficial vascular complex. MISCELLANEOUS LESIONS

Dermatofibromas present as firm dermal nodules with normal-appearing b u t hyperpigmented epidermis. On squeezing the lesion, one often sees a characteristic dimpling. These lesions are removed surgically for cosmetic reasons or when they are suspected to be something else. Acrochordons or skin tags are flesh-colored, often pedunculated overgrowths of soft connective tissue that can easily be 34

shaved off. Epidermal inclusion cysts, occasionally the residual of old ache, m a y become repeatedly inflamed or rarely infected. This is an indication for treatment, which should include removal of the cyst lining, since reaccumulation of the keratinous cyst contents may follow simple evacuation or partial removal. Surgical extirpation should be deferred until acute inflammation subsides.

CUTANEOUS SIGNS OF SYSTEMIC DISEASES The accessibility of the skin to detailed physical examinations allows the detection of subtle abnormalities t h a t m a y indicate systemic disease. Many of these cutaneous clues to internal diseases are presented in Table 5. It will not be possible to discuss all these skin signs of internal disease, but we will mention some of the more subtle and more important ones of which physicians should be aware. Any unilateral change in a nipple must be observed carefully. If an eczematous-appearing process does not respond promptly to topical steroids, a punch biopsy and often a m a m m o g r a m are mandatory, since the process m a y be Paget's disease, extension of an intraductal m a m m a r y carcinoma. It now is recognized t h a t the skin frequently is involved in amyloidosis. Biopsy of normal-appearing skin stained with Congo red often will yield the diagnosis on microscopic examination under polarized light. When signs occur secondary to amyloid involvement of the skin there may be a rather innocuous-appearing purpura, which is referred to at times as pinch purpura. Yellowish brown macules, plaques and papules of amyloid also may be seen. Nodular fat necrosis with pancreatic disease presumably is related to the release of pancreatic lipolytic enzymes. The clinical picture can be very similar to e r y t h e m a nodosum. Biopsy is definitive. Whereas e r y t h e m a nodosum shows a panniculitis, in nodular fat necrosis there is ghost-like necrosis of the fat cells. The glucagonoma syndrome occurs with carcinoma of the alpha cells of the pancreas. Increased glucagon levels are associated with an acral periorificial eczematous eruption. It 35

TABLE 5 . - C U T A N E O U S SIGNS OF SYSTEMIC DISEASES I. Internal Malignancy A. Skin infiltration by malignancy 1. Solid tumors: Can h a v e diverse morphology; a biopsy diagnosis 2. Paget's disease: This benign-looking eczematous process of the nipple is the extension of ductal carcinoma of the breast 3. Lymphoreticular malignancy: Hodgkin's disease rarely produces skin lesions b u t reticulum cell sarcoma commonly does 4. Leukemias: Skin infiltrate rare in acute lymphocytic and chronic granulocytic leukemias B. Skin lesions t h a t are p a r t of more widespread neoplasia 1. Arsenical keratoses: Arsenic is a carcinogen t h a t can cause p r i m a r y malignancy in m a n y organs 2. Kaposi's sarcoma: The skin is regularly involved but the t u m o r can be multicentric. GI tract is next most important site C. Skin changes due to metabolic products of a malignancy 1. Amyloid in multiple myeloma: Like p r i m a r y amyloidosis. Skin involved in about 40% of the patients 2. Carcinoid syndrome: Episodic flushing is first sign 3. Nodular fat necrosis: Secondary to pancreatic disease, including carcinoma 4. Glucagonoma syndrome: Rash associated with glucagonproducing tumor of the pancreas D. Idiopathic skin changes associated with malignancy 1. Dermatomyositis: Approximately 25% of adults with this have underlying malignancy 2. Acanthosis nigricans: There are hereditary and endocrinerelated cases as well as those reflecting adenocarcinoma 3. Exfoliative dermatitis: Lymphoma is one of m a n y causes II. Gastrointestinal Disease A. Inflammatory bowel disease 1. Pyoderma gangrenosum: Etiology not known. Usually responds dramatically to removal of inflamed bowel 2. E r y t h e m a nodosum: One of m a n y causes of tender red bumps on the legs B. Hepatic disease 1. J a u n d i c e 2. Vascular changes 3. Porphyria cutanea tarda: Only patients w i t h increased iron stores and a hereditary enzyme deficiency develop this process C. Syndromes 1. Hereditary hemorrhagic telangiectasia: Telangiectasia of the skin associated with GI bleeding 2. Peutz-Jeghers syndrome: Pigmented macules and h a m a r t o m a s of the small bowel 3. Gardner's syndrome: Multiple benign skin tumors associated with potentially m a l i g n a n t polyposis of the bowel 36

TABLE 5.-Continued III. Endocrine Disease A. Diabetes 1. Necrobiosis lipoidica diabeticorum: Often presents as orangebrown plaques, which develop central atrophy. Two-thirds of patients with this lesion are diabetic 2. Neuropathic ulcer: Ulcers resulting from sensory neuropathy B. Thyroid disease 1. Pretibial myxedema: Mucin in the dermis, sharply localized 2. Myxedema: Same mucin, but widespread in skin. Nonpitting edema C. Adrenal disease 1. Addison's disease: Pigmentation may be an important diagnostic clue 2. Cushing's disease: Hirsutism, acne, striae D. Pregnancy 1. Facial hyperpigmentation (melasma): Also occurs with oral contraceptives 2. Vascular changes: Varices, telangiectasia IV. Miscellaneous Metabolic Disease A. Scurvy: Vitamin C deficiency important in the synthesis of collagen and ground substance; leads to perifollicular hemorrhage B. Xanthomas 1. Eruptive xanthoma: In patients with high triglycerides 2. Tendinous and tuberous xanthoma: In patients with elevated cholesterol levels 3. Xanthelasma: In patients with normal lipids as well as Type II hyperlipoproteinemia C. Gout: Tophi usually in relatively avascular areas V. Miscellaneous Inborn Errors

A. Fabry's disease: Subtle telangiectasias herald this lipid-storage disease B. Tuberous sclerosis: Multiple skin lesions, including adenoma sebaceum and hypopigmented macules C. Ehlers-Danlos disease: Hyperextensible skin reflecting a generalized collagen defect VI. Miscellaneous A. Sarcoidosis: Skin lesions (excluding erythema nodosum) in about one-fourth of patients B. Urticaria pigmentosa: Positive Darier's sign is d i a g n o s t i c - a wheal after stroking the violaceous, macular and papular skin lesions C. Familial Mediterranean Fever (FMF): Erysipelas-like lesions

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is of interest t h a t this rash is similar to t h a t seen with zinc deficiency related either to total parenteral nutrition or acrodermatitis enteropathica. Although the glucagonoma rash does not respond to zinc, it does improve when the tumor regresses with treatment. Scurvy occasionally is seen in certain populations, such as elderly bachelor men. Recognition of the characteristic hyperkeratosis with perifollicular hemorrhages and hemorrhagic gingivitis should lead to determinations of ascorbic acid levels. Eruptive xanthomas are important lesions to recognize. They have the characteristic yellowish color of other xanthomas, but a much more impressive inflammatory component is present. One sees grouped yellowish papules on an erythematous base, primarily on the extensor surfaces of the extremities and the buttocks. These lesions are a manifestation of usually acute and impressively high serum triglycerides. The skin lesions of Fabry's disease, angiokeratoma, are subtle. They are small ( 3 - 4 mm) telangiectasias that tend to be grouped on the thighs, buttocks or scrotum or around the umbilicus. The patient m u s t be examined completely and under good lighting. It is not generally realized t h a t skin lesions, other t h a n those of amyloid, are seen in familial Mediterranean fever (FMF). In fact, during acute attacks, 10-20% of patients have characteristic erysipelas-like lesions. The patients are toxic and febrile, as is the case with erysipelas. However, the lesions do not progress as in erysipelas, and they often are on the lower extremities rather than on the face, as in erysipelas. This view of skin signs of internal disease is meant to emphasize the importance of careful examination of the skin as part of a physical examination rather t h a n to present an exhaustive listing of such signs. The reader is referred to an excellent text entitled Skin Signs of Systemic Disease by Dr. Irwin Braverman. 2

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ACK NOWLEDGMENTS W e w i s h to t h a n k D r s . P e t e r E. P o c h i a n d I r w i n M. F r e e d b e r g for c a r e f u l r e v i e w a n d s u g g e s t i o n s r e g a r d i n g t h i s m a n uscript. REFERENCES 1. Arndt, K. A.: Manual of Dermatologic Therapeutics (Boston: Little, Brown and Company, 1978). 2. Braverman, I. M.: Skin Signs of Systemic Disease (Philadelphia: W. B. Saunders Company, 1970). 3. Demis, D. J., Dobson, R. L., and McGuire, J. (eds.): ClinicalDermatology (Hagerstown, Md.: Harper & Row, 1978). 4. Fisher, A. A.: Contact Dermatitis (Philadelphia: Lea & Febiger, 1973). 5. Fitzpatrick, T. B., Arndt, K. A., Clark, W. C., Jr., Eisen, A. Z., Van Scott, E. J., and Vaughan, J. H. (eds.): Dermatology in General Medicine (New York: McGraw-Hill Book Company, 1971). 6. Moschella, S. L., Pillsbury, D. M., and Hurley, H. J., Jr.: Dermatology (Philadelphia: W. B. Saunders Company, 1975). 7. Rook, A., Wilkinson, D. S., and Ebling, F. J. G. (eds.): Textbook of Dermatology (2d ed.; Oxford: Blackwell Scientific Publications, 1972).

ANSWERS TO SELF-ASSESSMENT I.--1. 2. 3. 4. 5. II. - 1. 2. 3. 4. 5.

B. E. A. C. D.

III.-1. 2. 3. 4. 5.

D.

IV.-E.

E. A. B. C.

V.-A. VI.-B.

QUESTIONS

C. A. B. A. D.

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