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InternalMed_Harrison. Lichenification: A distinctive thickening of the skin that is characterized by accentuated skin-fold markings. Scale: Excessive accumulation of stratum corneum. Crust: Dried exudate of body fluids that may be either yellow (i.e., serous crust) or red (i.e., hemorrhagic crust). Erosion: Loss of epidermis without an associated loss of dermis. Ulcer: Loss of epidermis and at least a portion of the underlying dermis. Excoriation: Linear, angular erosions that may be covered by crust and are caused by scratching. Atrophy: An acquired loss of substance. In the skin, this may appear as a depression with intact epidermis (i.e., loss of dermal or subcutaneous tissue) or as sites of shiny, delicate, wrinkled lesions (i.e., epidermal atrophy). Scar: A change in the skin secondary to trauma or inflammation. Sites may be erythematous, hypopigmented, or hyperpigmented depending on their age or character. Sites on hair-bearing areas may be characterized by destruction of hair follicles.


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InternalMed_Harrison. Alopecia: Hair loss, partial or complete. Annular: Ring-shaped. Cyst: A soft, raised, encapsulated lesion filled with semisolid or liquid contents. Herpetiform: In a grouped configuration. Lichenoid eruption: Violaceous to purple, polygonal lesions that resemble those seen in lichen planus. Milia: Small, firm, white papules filled with keratin. Morbilliform rash: Generalized, small erythematous macules and/or papules that resemble lesions seen in measles. Nummular: Coin-shaped. Poikiloderma: Skin that displays variegated pigmentation, atrophy, and telangiectases. Polycyclic lesions: A configuration of skin lesions formed from coalescing rings or incomplete rings.


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InternalMed_Harrison. Poikiloderma: Skin that displays variegated pigmentation, atrophy, and telangiectases. Polycyclic lesions: A configuration of skin lesions formed from coalescing rings or incomplete rings. Pruritus: A sensation that elicits the desire to scratch. Pruritus is often the predominant symptom of inflammatory skin diseases (e.g., atopic dermatitis, allergic contact dermatitis); it is also commonly associated with xerosis and aged skin. Systemic conditions that can be associated with pruritus include chronic renal disease, cholestasis, pregnancy, malignancy, thyroid disease, polycythemia vera, and delusions of parasitosis. PART 2 Cardinal Manifestations and Presentation of Diseases APPROACH TO THE PATIENT:


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InternalMed_Harrison. In examining the skin it is usually advisable to assess the patient before taking an extensive history. This approach ensures that the entire cutaneous surface will be evaluated, and objective findings can be integrated with relevant historical data. Four basic features of a skin lesion must be noted and considered during a physical examination: the distribution of the eruption, the types of primary and secondary lesions, the shape of individual lesions, and the arrangement of the lesions. An ideal skin examination includes evaluation of the skin, hair, and nails as well as the mucous membranes of the mouth, eyes, nose, nasopharynx, and anogenital region. In the initial examination, it is important that the patient be disrobed as completely as possible to minimize chances of missing important individual skin lesions and permit accurate assessment of the distribution of the eruption. The patient should first be viewed from a distance of about 1.5–2 m (4–6 ft) so that the general


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InternalMed_Harrison. important individual skin lesions and permit accurate assessment of the distribution of the eruption. The patient should first be viewed from a distance of about 1.5–2 m (4–6 ft) so that the general character of the skin and the distribution of lesions can be evaluated. Indeed, the distribution of lesions often correlates highly with diagnosis (Fig. 70-6). For example, a hospitalized patient with a generalized erythematous exanthem is more likely to have a drug eruption than is a patient with a similar rash limited to the sun-exposed portions of the face. Once the distribution of the lesions has been established, the nature of the primary lesion


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InternalMed_Harrison. FIguRE 70-3 A schematic representation of several common primary skin lesions (see Table 70-1).


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InternalMed_Harrison. must be determined. Thus, when lesions are distributed on elbows, knees, and scalp, the most likely possibility based solely on distribution is psoriasis or dermatitis herpetiformis (Figs. 70-7 and 70-8, respectively). The primary lesion in psoriasis is a scaly papule that soon forms erythematous plaques covered with a white scale, whereas that of dermatitis herpetiformis is an urticarial papule that quickly becomes a small vesicle. In this manner, identification of the primary lesion directs the examiner toward the proper diagnosis. Secondary changes in skin can also be quite helpful. For example, scale represents excessive epidermis, while crust is the result of a discontinuous epithelial cell layer. Palpation of skin lesions can yield insight into the character of an eruption. Thus, red papules on the lower extremities that blanch with pressure can be a manifestation of many different diseases, but hemorrhagic red papules that do not blanch with pressure indicate palpable purpura


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InternalMed_Harrison. papules on the lower extremities that blanch with pressure can be a manifestation of many different diseases, but hemorrhagic red papules that do not blanch with pressure indicate palpable purpura characteristic of necrotizing vasculitis (Fig. 70-4).


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InternalMed_Harrison. The shape of lesions is also an important feature. Flat, round, erythematous papules and plaques are common in many cutaneous diseases. However, target-shaped lesions that consist in part of erythematous plaques are specific for erythema multiforme (Fig. 70-9). Likewise, the arrangement of individual lesions is important. Erythematous papules and vesicles can occur in many conditions, but their arrangement in a specific linear array suggests an external etiology such as allergic contact dermatitis (Fig. 70-10) or primary irritant dermatitis. In contrast, lesions with a generalized arrangement are common and suggest a systemic etiology. As in other branches of medicine, a complete history should be obtained to emphasize the following features: 1. Evolution of lesions a. Site of onset b. Manner in which the eruption progressed or spread c. d. Periods of resolution or improvement in chronic eruptions 2. Symptoms associated with the eruption a. Itching, burning, pain, numbness b.


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InternalMed_Harrison. Manner in which the eruption progressed or spread c. d. Periods of resolution or improvement in chronic eruptions 2. Symptoms associated with the eruption a. Itching, burning, pain, numbness b. What, if anything, has relieved symptoms c. Time of day when symptoms are most severe 3. Current or recent medications (prescribed as well as over-thecounter) 4. Associated systemic symptoms (e.g., malaise, fever, arthralgias) 5. 6. History of allergies 7. Presence of photosensitivity 8. Review of systems 9. Family history (particularly relevant for patients with melanoma, atopy, psoriasis, or acne) 10. Social, sexual, or travel history Many skin diseases can be diagnosed on the basis of gross clinical appearance, but sometimes relatively simple diagnostic procedures can yield valuable information. In most instances, they can be performed at the bedside with a minimum of equipment.


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InternalMed_Harrison. Skin Biopsy A skin biopsy is a straightforward minor surgical procedure; however, it is important to biopsy a lesion that is most likely to yield diagnostic findings. This decision may require expertise in skin diseases and knowledge of superficial anatomic structures in selected areas of the body. In this procedure, a small area of skin is anesthetized with 1% lidocaine with or without epinephrine. The skin lesion in question can be excised or saucerized with a scalpel or removed by punch biopsy. In the latter technique, a punch is pressed against the surface of the skin and rotated with downward pressure until it penetrates to the subcutaneous tissue. The circular biopsy is then lifted with forceps, and the bottom is cut with iris scissors. Biopsy sites may or may not need suture closure, depending on size and location.


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InternalMed_Harrison. KOH Preparation A potassium hydroxide (KOH) preparation is per-hyphae in dermatophyte infections, pseudohyphae and budding formed on scaling skin lesions where a fungal infection is suspected. yeasts in Candida infections, and “spaghetti and meatballs” yeast The edge of such a lesion is scraped gently with a no. 15 scalpel forms in tinea versicolor. The same sampling technique can be used blade. The removed scale is collected on a glass microscope slide to obtain scale for culture of selected pathogenic organisms. and then treated with 1 or 2 drops of a solution of 10–20% KOH. KOH dissolves keratin and allows easier visualization of fungal ele-Tzanck Smear A Tzanck smear is a cytologic technique most often ments. Brief heating of the slide accelerates dissolution of keratin. used in the diagnosis of herpesvirus infections (herpes simplex When the preparation is viewed under the microscope, the refractile virus [HSV] or varicella zoster virus [VZV]) (see Figs. 217-1 hyphae are seen


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InternalMed_Harrison. diagnosis of herpesvirus infections (herpes simplex When the preparation is viewed under the microscope, the refractile virus [HSV] or varicella zoster virus [VZV]) (see Figs. 217-1 hyphae are seen more easily when the light intensity is reduced and and 217-3). An early vesicle, not a pustule or crusted lesion, is the condenser is lowered. This technique can be used to identify unroofed, and the base of the lesion is scraped gently with a scalpel


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InternalMed_Harrison. PART 2 Cardinal Manifestations and Presentation of Diseases FIguRE 70-4 Necrotizing vasculitis. Palpable purpuric papules on the lower legs are seen in this patient with cutaneous small-vessel vasculitis. (Courtesy of Robert Swerlick, MD; with permission.) blade. The material is placed on a glass slide, air-dried, and stained with Giemsa or Wright’s stain. Multinucleated epithelial giant cells suggest the presence of HSV or VZV; culture, immunofluorescence microscopy, or genetic testing must be performed to identify the specific virus. FIguRE 70-5 Meningococcemia. An example of fulminant meningococcemia with extensive angular purpuric patches. (Courtesy of Stephen E. Gellis, MD; with permission.)


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InternalMed_Harrison. FIguRE 70-5 Meningococcemia. An example of fulminant meningococcemia with extensive angular purpuric patches. (Courtesy of Stephen E. Gellis, MD; with permission.) Diascopy Diascopy is designed to assess whether a skin lesion will blanch with pressure as, for example, in determining whether a red lesion is hemorrhagic or simply blood-filled. Urticaria (Fig. 70-11) will blanch with pressure, whereas a purpuric lesion caused by necrotizing vasculitis (Fig. 70-4) will not. Diascopy is performed by pressing a microscope slide or magnifying lens against a lesion and noting the amount of blanching that occurs. Granulomas often have an opaque to transparent, brown-pink “apple jelly” appearance on diascopy. Wood’s Light A Wood’s lamp generates 360-nm ultraviolet (“black”) light that can be used to aid the evaluation of certain skin disorders. FIguRE 70-6 Distribution of some common dermatologic diseases and lesions.


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InternalMed_Harrison. FIguRE 70-6 Distribution of some common dermatologic diseases and lesions. FIguRE 70-7 Psoriasis. This papulosquamous skin disease is charac-terized by small and large erythematous papules and plaques with overlying adherent silvery scale. FIguRE 70-10 Allergic contact dermatitis (ACD). A. An example of ACD in its acute phase, with sharply demarcated, weeping, eczema-tous plaques in a perioral distribution. B. ACD in its chronic phase, with an erythematous, lichenified, weeping plaque on skin chronically exposed to nickel in a metal snap. (B, Courtesy of Robert Swerlick, MD; with permission.) CHAPTER 70 Approach to the Patient with a Skin Disorder FIguRE 70-8 Dermatitis herpetiformis. This disorder typically displays pruritic, grouped papulovesicles on elbows, knees, buttocks, and posterior scalp. Vesicles are often excoriated due to associated pruritus.


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InternalMed_Harrison. For example, a Wood’s lamp will cause erythrasma (a superficial, intertriginous infection caused by Corynebacterium minutissimum) to show a characteristic coral pink color, and wounds colonized by Pseudomonas will appear pale blue. Tinea capitis caused by certain dermatophytes (e.g., Microsporum canis or M. audouinii) exhibits a yellow fluorescence. Pigmented lesions of the epidermis such as freckles are accentuated, while dermal pigment such as postinflammatory hyper-pigmentation fades under a Wood’s light. Vitiligo (Fig. 70-12) appears FIguRE 70-9 Erythema multiforme. This eruption is characterized by multiple erythematous plaques with a target or iris morphology. It usually represents a hypersensitivity reaction to drugs (e.g., sulfon-amides) or infections (e.g., HSV). (Courtesy of the Yale Resident’s Slide Collection; with permission.) FIguRE 70-11 Urticaria. Discrete and confluent, edematous, erythematous papules and plaques are characteristic of this whealing eruption.


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InternalMed_Harrison. FIguRE 70-11 Urticaria. Discrete and confluent, edematous, erythematous papules and plaques are characteristic of this whealing eruption. CLiniCAL fEATuRES of AToPiC DERMATiTiS FIguRE 70-12 Vitiligo. Characteristic lesions display an acral distribu-tion and striking depigmentation as a result of loss of melanocytes. totally white under a Wood’s lamp, and previously unsuspected areas of involvement often become apparent. A Wood’s lamp may also aid in the demonstration of tinea versicolor and in recognition of ash leaf spots in patients with tuberous sclerosis.


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InternalMed_Harrison. Patch Tests Patch testing is designed to document sensitivity to a specific antigen. In this procedure, a battery of suspected allergens is applied to the patient’s back under occlusive dressings and allowed to remain in contact with the skin for 48 h. The dressings are removed, and the area is examined for evidence of delayed hypersensitivity reactions (e.g., erythema, edema, or papulovesicles). This test is best performed by physicians with special expertise in patch testing and is often helpful in the evaluation of patients with chronic dermatitis. Eczema, Psoriasis, Cutaneous infections, Acne, and other Common Skin Disorders Leslie P. Lawley, Calvin O. McCall, Thomas J. Lawley ECZEMA AND DERMATITIS 71


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InternalMed_Harrison. Eczema, Psoriasis, Cutaneous infections, Acne, and other Common Skin Disorders Leslie P. Lawley, Calvin O. McCall, Thomas J. Lawley ECZEMA AND DERMATITIS 71 Eczema is a type of dermatitis, and these terms are often used synonymously (e.g., atopic eczema or atopic dermatitis [AD]). Eczema is a reaction pattern that presents with variable clinical findings and the common histologic finding of spongiosis (intercellular edema of the epidermis). Eczema is the final common expression for a number of disorders, including those discussed in the following sections. Primary lesions may include erythematous macules, papules, and vesicles, which can coalesce to form patches and plaques. In severe eczema, secondary lesions from infection or excoriation, marked by weeping and crusting, may predominate. In chronic eczematous conditions, lichenification (cutaneous hypertrophy and accentuation of normal skin markings) may alter the characteristic appearance of eczema.


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InternalMed_Harrison. AD is the cutaneous expression of the atopic state, characterized by a family history of asthma, allergic rhinitis, or eczema. The prevalence of AD is increasing worldwide. Some of its features are shown in Table 71-1. The etiology of AD is only partially defined, but there is a clear genetic predisposition. When both parents are affected by AD, >80% of their children manifest the disease. When only one parent is affected, the prevalence drops to slightly over 50%. A characteristic defect in AD that contributes to the pathophysiology is an PART 2 Cardinal Manifestations and Presentation of Diseases 1. 2. 3. Lesions typical of eczematous dermatitis 4. Personal or family history of atopy (asthma, allergic rhinitis, food allergies, or eczema) 5. 6.


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InternalMed_Harrison. 2. 3. Lesions typical of eczematous dermatitis 4. Personal or family history of atopy (asthma, allergic rhinitis, food allergies, or eczema) 5. 6. Lichenification of skin impaired epidermal barrier. In many patients, a mutation in the gene encoding filaggrin, a structural protein in the stratum corneum, is responsible. Patients with AD may display a variety of immunoregulatory abnormalities, including increased IgE synthesis; increased serum IgE levels; and impaired, delayed-type hypersensitivity reactions.


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InternalMed_Harrison. The clinical presentation often varies with age. Half of patients with AD present within the first year of life, and 80% present by 5 years of age. About 80% ultimately coexpress allergic rhinitis or asthma. The infantile pattern is characterized by weeping inflammatory patches and crusted plaques on the face, neck, and extensor surfaces. The childhood and adolescent pattern is typified by dermatitis of flexural skin, particularly in the antecubital and popliteal fossae (Fig. 71-1). AD may resolve spontaneously, but approximately 40% of all individuals affected as children will have dermatitis in adult life. The distribution of lesions in adults may be similar to those seen in childhood; however, adults frequently have localized disease manifesting as lichen simplex chronicus or hand eczema (see below). In patients with localized disease, AD may be suspected because of a typical personal or family history or the presence of cutaneous stigmata of AD such as perioral pallor, an extra


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InternalMed_Harrison. (see below). In patients with localized disease, AD may be suspected because of a typical personal or family history or the presence of cutaneous stigmata of AD such as perioral pallor, an extra fold of skin beneath the lower eyelid (Dennie-Morgan folds), increased palmar skin markings, and an increased incidence of cutaneous infections, particularly with Staphylococcus aureus. Regardless of other manifestations, pruritus is a prominent characteristic of AD in all age groups and is exacerbated by dry skin. Many of the cutaneous findings in affected patients, such as lichenification, are secondary to rubbing and scratching.


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InternalMed_Harrison. Therapy for AD should include avoidance of cutaneous irritants, adequate moisturizing through the application of emollients, judicious use of topical anti-inflammatory agents, and prompt treatment of secondary infection. Patients should be instructed to bathe no more often than daily, using warm or cool water, and to use only mild bath soap. Immediately after bathing, while the skin is still moist, a topical anti-inflammatory agent in a cream or ointment base should be applied to areas of dermatitis, and all other skin areas should be lubricated with a moisturizer. Approximately 30 g of a topical agent is required to cover the entire body surface of an average adult. FIguRE 71-1 Atopic dermatitis. Hyperpigmentation, lichenification, and scaling in the antecubital fossae are seen in this patient with atopic dermatitis. (Courtesy of Robert Swerlick, MD; with permission.)


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InternalMed_Harrison. Lowto mid-potency topical glucocorticoids are employed in most treatment regimens for AD. Skin atrophy and the potential for systemic absorption are constant concerns, especially with more potent agents. Low-potency topical glucocorticoids or nonglucocorticoid anti-inflammatory agents should be selected for use on the face and in intertriginous areas to minimize the risk of skin atrophy. Two nonglucocorticoid anti-inflammatory agents are available: tacrolimus ointment and pimecrolimus cream. These agents are macrolide immunosuppressants that are approved by the U.S. Food and Drug Administration (FDA) for topical use in AD. Reports of broader effectiveness appear in the literature. These agents do not cause skin atrophy, nor do they suppress the hypothalamic-pituitary-adrenal axis. However, concerns have emerged regarding the potential for lymphomas in patients treated with these agents. Thus, caution should be exercised when these agents are considered. Currently, they are also more


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InternalMed_Harrison. concerns have emerged regarding the potential for lymphomas in patients treated with these agents. Thus, caution should be exercised when these agents are considered. Currently, they are also more costly than topical glucocorticoids. Barrier-repair products that attempt to restore the impaired epidermal barrier are also nonglucocorticoid agents and are gaining popularity in the treatment of AD.


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InternalMed_Harrison. Secondary infection of eczematous skin may lead to exacerbation of AD. Crusted and weeping skin lesions may be infected with S. aureus. When secondary infection is suspected, eczematous lesions should be cultured and patients treated with systemic antibiotics active against S. aureus. The initial use of penicillinase-resistant penicillins or cephalosporins is preferable. Dicloxacillin or cephalexin (250 mg qid for 7–10 days) is generally adequate for adults; however, antibiotic selection must be directed by culture results and clinical response. More than 50% of S. aureus isolates are now methicillin resistant in some communities. Current recommendations for the treatment of infection with these community-acquired methicillinresistant S. aureus (CA-MRSA) strains in adults include trimethoprimsulfamethoxazole (1 double-strength tablet bid), minocycline (100 mg bid), doxycycline (100 mg bid), or clindamycin (300–450 mg qid). Duration of therapy should be 7–10 days. Inducible resistance


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InternalMed_Harrison. (1 double-strength tablet bid), minocycline (100 mg bid), doxycycline (100 mg bid), or clindamycin (300–450 mg qid). Duration of therapy should be 7–10 days. Inducible resistance may limit clindamycin’s usefulness. Such resistance can be detected by the double-disk diffusion test, which should be ordered if the isolate is erythromycin resistant and clindamycin sensitive. As an adjunct, antibacterial washes or dilute sodium hypochlorite baths (0.005% bleach) and intermittent nasal mupirocin may be useful.


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InternalMed_Harrison. Control of pruritus is essential for treatment, because AD often represents “an itch that rashes.” Antihistamines are most often used to control pruritus. Diphenhydramine (25 mg every 4–6 h), hydroxyzine (10–25mg every 6 h), or doxepin (10–25 mg at bedtime) are useful primarily due to their sedating action. Higher doses of these agents may be required, but sedation can become bothersome. Patients need to be counseled about driving or operating heavy equipment after taking these medications. When used at bedtime, sedating antihistamines may improve the patient’s sleep. Although they are effective in urticaria, non-sedating antihistamines and selective H2 blockers are of little use in controlling the pruritus of AD.


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InternalMed_Harrison. Treatment with systemic glucocorticoids should be limited to severe exacerbations unresponsive to topical therapy. In the patient with chronic AD, therapy with systemic glucocorticoids will generally clear the skin only briefly, and cessation of the systemic therapy will invariably be accompanied by a return, if not a worsening, of the dermatitis. Patients who do not respond to conventional therapies should be considered for patch testing to rule out allergic contact dermatitis (ACD). The role of dietary allergens in AD is controversial, and there is little evidence that they play any role outside of infancy, during which a small percentage of patients with AD may be affected by food allergens.


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InternalMed_Harrison. Lichen simplex chronicus may represent the end stage of a variety of pruritic and eczematous disorders, including AD. It consists of a circumscribed plaque or plaques of lichenified skin due to chronic 345 scratching or rubbing. Common areas involved include the posterior nuchal region, dorsum of the feet, and ankles. Treatment of lichen simplex chronicus centers on breaking the cycle of chronic itching and scratching. High-potency topical glucocorticoids are helpful in most cases, but, in recalcitrant cases, application of topical glucocorticoids under occlusion, or intralesional injection of glucocorticoids may be required.


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InternalMed_Harrison. Contact dermatitis is an inflammatory skin process caused by an exogenous agent or agents that directly or indirectly injure the skin. In irritant contact dermatitis (ICD), this injury is caused by an inherent characteristic of a compound—for example, a concentrated acid or base. Agents that cause ACD induce an antigen-specific immune response (e.g., poison ivy dermatitis). The clinical lesions of contact dermatitis may be acute (wet and edematous) or chronic (dry, thickened, and scaly), depending on the persistence of the insult (see Fig. 70-10).


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InternalMed_Harrison. Irritant Contact Dermatitis ICD is generally well demarcated and often localized to areas of thin skin (eyelids, intertriginous areas) or to areas where the irritant was occluded. Lesions may range from minimal skin erythema to areas of marked edema, vesicles, and ulcers. Prior exposure to the offending agent is not necessary, and the reaction develops in minutes to a few hours. Chronic low-grade irritant dermatitis is the most common type of ICD, and the most common area of involvement is the hands (see below). The most common irritants encountered are chronic wet work, soaps, and detergents. Treatment should be directed toward the avoidance of irritants and the use of protective gloves or clothing.


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InternalMed_Harrison. Allergic Contact Dermatitis ACD is a manifestation of delayed-type hypersensitivity mediated by memory T lymphocytes in the skin. Prior exposure to the offending agent is necessary to develop the hypersensitivity reaction, which may take as little as 12 h or as much as 72 h to develop. The most common cause of ACD is exposure to plants, especially to members of the family Anacardiaceae, including the genus Toxicodendron. Poison ivy, poison oak, and poison sumac are members of this genus and cause an allergic reaction marked by erythema, vesiculation, and severe pruritus. The eruption is often linear or angular, corresponding to areas where plants have touched the skin. The sensitizing antigen common to these plants is urushiol, an oleoresin containing the active ingredient pentadecylcatechol. The oleoresin may adhere to skin, clothing, tools, and pets, and contaminated articles may cause dermatitis even after prolonged storage. Blister fluid does not contain urushiol and is not


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InternalMed_Harrison. The oleoresin may adhere to skin, clothing, tools, and pets, and contaminated articles may cause dermatitis even after prolonged storage. Blister fluid does not contain urushiol and is not capable of inducing skin eruption in exposed subjects.


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InternalMed_Harrison. If contact dermatitis is suspected and an offending agent is identified and removed, the eruption will resolve. Usually, treatment with high-potency topical glucocorticoids is enough to relieve symptoms while the dermatitis runs its course. For those patients who require systemic therapy, daily oral prednisone—beginning at 1 mg/kg, but usually ≤60 mg/d—is sufficient. The dose should be tapered over 2–3 weeks, and each daily dose should be taken in the morning with food.


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InternalMed_Harrison. Identification of a contact allergen can be a difficult and time-consuming task. Allergic contact dermatitis should be suspected in patients with dermatitis unresponsive to conventional therapy or with an unusual and patterned distribution. Patients should be questioned carefully regarding occupational exposures and topical medications. Common sensitizers include preservatives in topical preparations, nickel sulfate, potassium dichromate, thimerosal, neomycin sulfate, fragrances, formaldehyde, and rubber-curing agents. Patch testing is helpful in identifying these agents but should not be attempted when patients have widespread active dermatitis or are taking systemic glucocorticoids. CHAPTER 71 Eczema, Psoriasis, Cutaneous Infections, Acne, and Other Common Skin Disorders PART 2 Cardinal Manifestations and Presentation of Diseases


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InternalMed_Harrison. CHAPTER 71 Eczema, Psoriasis, Cutaneous Infections, Acne, and Other Common Skin Disorders PART 2 Cardinal Manifestations and Presentation of Diseases FIguRE 71-2 Dyshidrotic eczema. This example is characterized by deep-seated vesicles and scaling on palms and lateral fingers, and the disease is often associated with an atopic diathesis.


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InternalMed_Harrison. Hand eczema is a very common, chronic skin disorder in which both exogenous and endogenous factors play important roles. It may be associated with other cutaneous disorders such as AD, and contact with various agents may be involved. Hand eczema represents a large proportion of cases of occupation-associated skin disease. Chronic, excessive exposure to water and detergents, harsh chemicals, or allergens may initiate or aggravate this disorder. It may present with dryness and cracking of the skin of the hands as well as with variable amounts of erythema and edema. Often, the dermatitis will begin under rings, where water and irritants are trapped. Dyshidrotic eczema, a variant of hand eczema, presents with multiple, intensely pruritic, small papules and vesicles on the thenar and hypothenar eminences and the sides of the fingers (Fig. 71-2). Lesions tend to occur in crops that slowly form crusts and then heal.


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InternalMed_Harrison. The evaluation of a patient with hand eczema should include an assessment of potential occupation-associated exposures. The history should be directed to identifying possible irritant or allergen exposures. Therapy for hand eczema is directed toward avoidance of irritants, identification of possible contact allergens, treatment of coexistent infection, and application of topical glucocorticoids. Whenever possible, the hands should be protected by gloves, preferably vinyl. The use of rubber gloves (latex) to protect dermatitic skin is sometimes associated with the development of hypersensitivity reactions to components of the gloves. Patients can be treated with cool moist compresses followed by application of a midto high-potency topical glucocorticoid in a cream or ointment base. As in AD, treatment of secondary infection is essential for good control. In addition, patients with hand eczema should be examined for dermatophyte infection by KOH preparation and culture (see below).


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InternalMed_Harrison. Nummular eczema is characterized by circular or oval “coinlike” lesions, beginning as small edematous papules that become crusted and scaly. The etiology of nummular eczema is unknown, but dry skin is a contributing factor. Common locations are the trunk or the extensor surfaces of the extremities, particularly on the pretibial areas or dorsum of the hands. Nummular eczema occurs more frequently in men and is most common in middle age. The treatment of nummular eczema is similar to that for AD.


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InternalMed_Harrison. Asteatotic eczema, also known as xerotic eczema or “winter itch,” is a mildly inflammatory dermatitis that develops in areas of extremely dry skin, especially during the dry winter months. Clinically, there may be considerable overlap with nummular eczema. This form of eczema accounts for a large number of physician visits because of the associated pruritus. Fine cracks and scale, with or without erythema, characteristically develop in areas of dry skin, especially on the anterior surfaces of the lower extremities in elderly patients. Asteatotic eczema responds well to topical moisturizers and the avoidance of cutaneous irritants. Overbathing and the use of harsh soaps exacerbate asteatotic eczema.


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InternalMed_Harrison. Stasis dermatitis develops on the lower extremities secondary to venous incompetence and chronic edema. Patients may give a history of deep venous thrombosis and may have evidence of vein removal or varicose veins. Early findings in stasis dermatitis consist of mild erythema and scaling associated with pruritus. The typical initial site of involvement is the medial aspect of the ankle, often over a distended vein (Fig. 71-3).


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InternalMed_Harrison. Stasis dermatitis may become acutely inflamed, with crusting and exudate. In this state, it is easily confused with cellulitis. Chronic stasis dermatitis is often associated with dermal fibrosis that is recognized clinically as brawny edema of the skin. As the disorder progresses, the dermatitis becomes progressively pigmented due to chronic erythrocyte extravasation leading to cutaneous hemosiderin deposition. Stasis dermatitis may be complicated by secondary infection and contact dermatitis. Severe stasis dermatitis may precede the development of stasis ulcers.


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InternalMed_Harrison. Patients with stasis dermatitis and stasis ulceration benefit greatly from leg elevation and the routine use of compression stockings with a gradient of at least 30–40 mmHg. Stockings providing less compression, such as antiembolism hose, are poor substitutes. Use of emollients and/or mid-potency topical glucocorticoids and avoidance of irritants are also helpful in treating stasis dermatitis. Protection of the legs from injury, including scratching, and control of chronic edema are essential to prevent ulcers. Diuretics may be required to adequately control chronic edema.


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InternalMed_Harrison. Stasis ulcers are difficult to treat, and resolution is slow. It is extremely important to elevate the affected limb as much as possible. The ulcer should be kept clear of necrotic material by gentle debridement and covered with a semipermeable dressing and a compression dressing or compression stocking. Glucocorticoids should not be applied to ulcers, because they may retard healing; however, they may be applied to the surrounding skin to control itching, scratching, and additional trauma. Secondarily infected lesions should be treated with appropriate oral antibiotics, but it should be noted that all ulcers will become colonized with bacteria, and the purpose of antibiotic therapy should not be to clear all bacterial growth. Care must be taken to exclude treatable causes of leg ulcers (hypercoagulation, vasculitis) before beginning the chronic management outlined above.


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InternalMed_Harrison. FIguRE 71-3 Stasis dermatitis. An example of stasis dermatitis showing erythematous, scaly, and oozing patches over the lower leg. Several stasis ulcers are also seen in this patient. FIguRE 71-4 Seborrheic dermatitis. Central facial erythema with overlying greasy, yellowish scale is seen in this patient. (Courtesy of Jean Bolognia, MD; with permission.)


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InternalMed_Harrison. FIguRE 71-4 Seborrheic dermatitis. Central facial erythema with overlying greasy, yellowish scale is seen in this patient. (Courtesy of Jean Bolognia, MD; with permission.) Seborrheic dermatitis is a common, chronic disorder characterized by greasy scales overlying erythematous patches or plaques. Induration and scale are generally less prominent than in psoriasis, but clinical overlap exists between these diseases (“sebopsoriasis”). The most common location is in the scalp, where it may be recognized as severe dandruff. On the face, seborrheic dermatitis affects the eyebrows, eyelids, glabella, and nasolabial folds (Fig. 71-4). Scaling of the external auditory canal is common in seborrheic dermatitis. In addition, the postauricular areas often become macerated and tender. Seborrheic dermatitis may also develop in the central chest, axilla, groin, submammary folds, and gluteal cleft. Rarely, it may cause widespread generalized dermatitis. Pruritus is variable.


InternalMed_Harrison

InternalMed_Harrison. Seborrheic dermatitis may be evident within the first few weeks of life, and within this context it typically occurs in the scalp (“cradle cap”), face, or groin. It is rarely seen in children beyond infancy but becomes evident again during adult life. Although it is frequently seen in patients with Parkinson’s disease, in those who have had cerebrovascular accidents, and in those with HIV infection, the overwhelming majority of individuals with seborrheic dermatitis have no underlying disorder.


InternalMed_Harrison

InternalMed_Harrison. Treatment with low-potency topical glucocorticoids in conjunction with a topical antifungal agent, such as ketoconazole cream or ciclopirox cream, is often effective. The scalp and beard areas may benefit from antidandruff shampoos, which should be left in place 3–5 min before rinsing. High-potency topical glucocorticoid solutions (betamethasone or clobetasol) are effective for control of severe scalp involvement. High-potency glucocorticoids should not be used on the face because this treatment is often associated with steroid-induced rosacea or atrophy.


InternalMed_Harrison

InternalMed_Harrison. Psoriasis is one of the most common dermatologic diseases, affecting up to 2% of the world’s population. It is an immune-mediated disease clinically characterized by erythematous, sharply demarcated papules and rounded plaques covered by silvery micaceous scale. The skin lesions of psoriasis are variably pruritic. Traumatized areas often develop lesions of psoriasis (the Koebner or isomorphic phenomenon). In addition, other external factors may exacerbate psoriasis, including infections, stress, and medications (lithium, beta blockers, and antimalarial drugs).


InternalMed_Harrison

InternalMed_Harrison. The most common variety of psoriasis is called plaque-type. Patients with plaque-type psoriasis have stable, slowly enlarging plaques, which remain basically unchanged for long periods of time. The most commonly involved areas are the elbows, knees, gluteal cleft, and scalp. Involvement tends to be symmetric. Plaque psoriasis generally develops slowly and runs an indolent course. It rarely remits spontaneously. Inverse psoriasis affects the intertriginous regions, including the axilla, groin, submammary region, and navel; it also tends to affect the scalp, palms, and soles. The individual lesions are sharply demarcated plaques (see Fig. 70-7), but they may be moist and without scale due to their locations.


InternalMed_Harrison

InternalMed_Harrison. Guttate psoriasis (eruptive psoriasis) is most common in children and young adults. It develops acutely in individuals without psoriasis or in those with chronic plaque psoriasis. Patients present with many small erythematous, scaling papules, frequently after upper respiratory tract infection with β-hemolytic streptococci. The differential diagnosis should include pityriasis rosea and secondary syphilis.


InternalMed_Harrison

InternalMed_Harrison. In pustular psoriasis, patients may have disease localized to the palms and soles, or the disease may be generalized. Regardless of the extent of disease, the skin is erythematous, with pustules and variable scale. Localized to the palms and soles, it is easily confused with eczema. When it is generalized, episodes are characterized by fever (39°–40°C [102.2°–104.0°F]) lasting several days, an accompanying generalized eruption of sterile pustules, and a background of intense erythema; patients may become erythrodermic. Episodes of fever and pustules are recurrent. Local irritants, pregnancy, medications, infections, and systemic glucocorticoid withdrawal can precipitate this form of psoriasis. Oral retinoids are the treatment of choice in nonpregnant patients. CHAPTER 71 Eczema, Psoriasis, Cutaneous Infections, Acne, and Other Common Skin Disorders


InternalMed_Harrison

InternalMed_Harrison. CHAPTER 71 Eczema, Psoriasis, Cutaneous Infections, Acne, and Other Common Skin Disorders Psoriasis Sharply demarcated, erythematous plaques with mica-like scale; predominantly on elbows, knees, and scalp; atypical forms may localize to intertriginous areas; eruptive forms may be associated with infection Lichen planus Purple polygonal papules marked by severe pruritus; lacy white markings, especially associated with mucous membrane lesions Pityriasis rosea Rash often preceded by herald patch; oval to round plaques with trailing scale; most often affects trunk; eruption lines up in skinfolds giving a “fir tree–like” appearance; generally spares palms and soles Dermatophytosis Polymorphous appearance depending on dermatophyte, body site, and host response; sharply defined to ill-demarcated scaly plaques with or without inflammation; may be associated with hair loss May be aggravated by certain drugs, infection; severe forms seen in association with HIV


InternalMed_Harrison

InternalMed_Harrison. Certain drugs may induce: thiazides, antimalarial drugs Variable pruritus; self-limited, resolving in 2–8 weeks; may be imitated by secondary syphilis KOH preparation may show branching hyphae; culture helpful Acanthosis, vascular proliferation PART 2 Cardinal Manifestations and Presentation of Diseases Fingernail involvement, appearing as punctate pitting, onycholysis, nail thickening, or subungual hyperkeratosis, may be a clue to the diagnosis of psoriasis when the clinical presentation is not classic.


InternalMed_Harrison

InternalMed_Harrison. According to the National Psoriasis Foundation, up to 30% of patients with psoriasis have psoriatic arthritis (PsA). There are five subtypes of PsA: symmetric, asymmetric, distal interphalangeal predominant (DIP), spondylitis, and arthritis mutilans. Symmetric arthritis resembles rheumatoid arthritis, but is usually milder. Asymmetric arthritis can involve any joint and may present as “sausage digits.” DIP is the classic form, but occurs in only about 5% of patients with PsA. It may involve fingers and toes. Spondylitis also occurs in about 5% of patients with PsA. Arthritis mutilans is severe and deforming. It affects primarily the small joints of the hands and feet. It accounts for fewer than 5% of PsA cases.


InternalMed_Harrison

InternalMed_Harrison. An increased risk of metabolic syndrome, including increased morbidity and mortality from cardiovascular events, has been demonstrated in psoriasis patients. Appropriate screening tests should be performed. The etiology of psoriasis is still poorly understood, but there is clearly a genetic component to the disease. In various studies, 30–50% of patients with psoriasis report a positive family history. Psoriatic lesions contain infiltrates of activated T cells that are thought to elaborate cytokines responsible for keratinocyte hyperproliferation, which results in the characteristic clinical findings. Agents inhibiting T cell activation, clonal expansion, or release of proinflammatory cytokines are often effective for the treatment of severe psoriasis (see below).


InternalMed_Harrison

InternalMed_Harrison. Treatment of psoriasis depends on the type, location, and extent of disease. All patients should be instructed to avoid excess drying or irritation of their skin and to maintain adequate cutaneous hydration. Most cases of localized, plaque-type psoriasis can be managed with mid-potency topical glucocorticoids, although their long-term use is often accompanied by loss of effectiveness (tachyphylaxis) and atrophy of the skin. A topical vitamin D analogue (calcipotriene) and a retinoid (tazarotene) are also efficacious in the treatment of limited psoriasis and have largely replaced other topical agents such as coal tar, salicylic acid, and anthralin.


InternalMed_Harrison

InternalMed_Harrison. Ultraviolet (UV) light, natural or artificial, is an effective therapy for many patients with widespread psoriasis. Ultraviolet B (UVB), narrowband UVB, and ultraviolet A (UVA) light with either oral or topical psoralens (PUVA) is used clinically. UV light’s immunosuppressive properties are thought to be responsible for its therapeutic activity in psoriasis. It is also mutagenic, potentially leading to an increased incidence of nonmelanoma and melanoma skin cancer. UV-light therapy is contraindicated in patients receiving cyclosporine and should be used with great care in all immunocompromised patients due to the increased risk of skin cancer.


InternalMed_Harrison

InternalMed_Harrison. Various systemic agents can be used for severe, widespread psoriatic disease (Table 71-3). Oral glucocorticoids should not be used for the treatment of psoriasis due to the potential for development of life-threatening pustular psoriasis when therapy is discontinued. Methotrexate is an effective agent, especially in patients with psoriatic arthritis. The synthetic retinoid acitretin is useful, especially when immunosuppression must be avoided; however, teratogenicity limits its use.


InternalMed_Harrison

InternalMed_Harrison. The evidence implicating psoriasis as a T cell–mediated disorder has directed therapeutic efforts to immunoregulation. Cyclosporine and other immunosuppressive agents can be very effective in the treatment of psoriasis, and much attention is currently directed toward the development of biologic agents with more selective immunosuppressive properties and better safety profiles (Table 71-4). Experience with these biologic agents is limited, and information regarding combination therapy and adverse events continues to emerge. Use of tumor necrosis factor (TNF-α) inhibitors may worsen congestive heart failure (CHF), and they should be used with caution in patients at risk for or known to have CHF. Further, none of the immunosuppressive agents used in the treatment of psoriasis should be initiated if the patient has a severe infection; patients on such therapy should be routinely screened for tuberculosis. There have been reports of progressive multifocal leukoencephalopathy in association


InternalMed_Harrison

InternalMed_Harrison. if the patient has a severe infection; patients on such therapy should be routinely screened for tuberculosis. There have been reports of progressive multifocal leukoencephalopathy in association with treatment with the TNF-α inhibitors. Malignancies, including a risk or history of certain malignancies, may limit the use of these systemic agents.


InternalMed_Harrison

InternalMed_Harrison. Administration Agent Mechanism of Action Indication Route Frequency Warnings Abbreviations: CHF, congestive heart failure; IL, interleukin; IM, intramuscular; Ps, psoriasis; PsA, psoriatic arthritis; SC, subcutaneous; TNF, tumor necrosis factor. FIguRE 71-5 Lichen planus. An example of lichen planus showing multiple flat-topped, violaceous papules and plaques. Nail dystrophy, as seen in this patient’s thumbnail, may also be a feature. (Courtesy of Robert Swerlick, MD; with permission.)


InternalMed_Harrison

InternalMed_Harrison. Lichen planus (LP) is a papulosquamous disorder that may affect the skin, scalp, nails, and mucous membranes. The primary cutaneous lesions are pruritic, polygonal, flat-topped, violaceous papules. Close examination of the surface of these papules often reveals a network of gray lines (Wickham’s striae). The skin lesions may occur anywhere but have a predilection for the wrists, shins, lower back, and genitalia (Fig. 71-5). Involvement of the scalp (lichen planopilaris) may lead to scarring alopecia, and nail involvement may lead to permanent deformity or loss of fingernails and toenails. LP commonly involves mucous membranes, particularly the buccal mucosa, where it can present on a spectrum ranging from a mild, white, reticulate eruption of the mucosa to a severe, erosive stomatitis. Erosive stomatitis may persist for years and may be linked to an increased risk of oral squamous cell carcinoma. Cutaneous eruptions clinically resembling LP have been observed after administration of


InternalMed_Harrison

InternalMed_Harrison. stomatitis may persist for years and may be linked to an increased risk of oral squamous cell carcinoma. Cutaneous eruptions clinically resembling LP have been observed after administration of numerous drugs, including thiazide diuretics, gold, antimalarial agents, penicillamine, and phenothiazines, and in patients with skin lesions of chronic graft-versus-host disease. In addition, LP may be associated with hepatitis C infection. The course of LP is variable, but most patients have spontaneous remissions 6 months to 2 years after the onset of disease. Topical glucocorticoids are the mainstay of therapy.


InternalMed_Harrison

InternalMed_Harrison. Pityriasis rosea (PR) is a papulosquamous eruption of unknown etiology occurring more commonly in the spring and fall. Its first manifestation is the development of a 2to 6-cm annular lesion (the herald patch). This is followed in a few days to a few weeks by the appearance of many smaller annular or papular lesions with a predilection to occur on the trunk (Fig. 71-6). The lesions are generally oval, with their long axis parallel to the skinfold lines. Individual lesions may range in color from red to brown and have a trailing scale. PR shares many clinical features with the eruption of secondary syphilis, but palm and sole lesions are extremely rare in PR and common in secondary syphilis. The eruption tends to be moderately pruritic and lasts 3–8 weeks. Treatment is directed at alleviating pruritus and consists of oral antihistamines; mid-potency topical glucocorticoids; and, in some cases, UVB phototherapy. IMPETIgO, ECTHYMA, AND FuRuNCuLOSIS


InternalMed_Harrison

InternalMed_Harrison. IMPETIgO, ECTHYMA, AND FuRuNCuLOSIS Impetigo is a common superficial bacterial infection of skin caused most often by S. aureus (Chap. 172) and in some cases by group A β-hemolytic streptococci (Chap. 173). The primary lesion is a superficial pustule that ruptures and forms a characteristic yellow-brown FIguRE 71-6 Pityriasis rosea. In this patient with pityriasis rosea, multiple round to oval erythematous patches with fine central scale are distributed along the skin tension lines on the trunk.


InternalMed_Harrison

InternalMed_Harrison. honey-colored crust (see Fig. 173-3). Lesions may occur on normal skin (primary infection) or in areas already affected by another skin disease (secondary infection). Lesions caused by staphylococci may be tense, clear bullae, and this less common form of the disease is called bullous impetigo. Blisters are caused by the production of exfoliative toxin by S. aureus phage type II. This is the same toxin responsible for staphylococcal scalded-skin syndrome, often resulting in dramatic loss of the superficial epidermis due to blistering. The latter syndrome is much more common in children than in adults; however, it should be considered along with toxic epidermal necrolysis and severe drug eruptions in patients with widespread blistering of the skin. Ecthyma is a deep non-bullous variant of impetigo that causes punched-out ulcerative lesions. It is more often caused by a primary or secondary infection with Streptococcus pyogenes. Ecthyma is a deeper infection than typical impetigo and


InternalMed_Harrison

InternalMed_Harrison. impetigo that causes punched-out ulcerative lesions. It is more often caused by a primary or secondary infection with Streptococcus pyogenes. Ecthyma is a deeper infection than typical impetigo and resolves with scars. Treatment of both ecthyma and impetigo involves gentle debridement of adherent crusts, which is facilitated by the use of soaks and topical antibiotics in conjunction with appropriate oral antibiotics.


InternalMed_Harrison

InternalMed_Harrison. Furunculosis is also caused by S. aureus, and this disorder has gained prominence in the last decade because of CA-MRSA. A furuncle, or boil, is a painful, erythematous nodule that can occur on any cutaneous surface. The lesions may be solitary but are most often multiple. Patients frequently believe they have been bitten by spiders or insects. Family members or close contacts may also be affected. Furuncles can rupture and drain spontaneously or may need incision and drainage, which may be adequate therapy for small solitary furuncles without cellulitis or systemic symptoms. Whenever possible, lesional material should be sent for culture. Current recommendations for methicillinsensitive infections are β-lactam antibiotics. Therapy for CA-MRSA was discussed previously (see “Atopic Dermatitis”). Warm compresses and nasal mupirocin are helpful therapeutic additions. Severe infections may require IV antibiotics. See Chap. 156.


InternalMed_Harrison

InternalMed_Harrison. See Chap. 156. Dermatophytes are fungi that infect skin, hair, and nails and include members of the genera Trichophyton, Microsporum, and Epidermophyton (Chap. 243). Tinea corporis, or infection of the relatively hairless skin of the body (glabrous skin), may have a variable appearance depending on the extent of the associated inflammatory reaction. Typical infections consist of erythematous, scaly plaques, with an annular appearance that accounts for the common name “ringworm.” Deep inflammatory nodules or granulomas occur in CHAPTER 71 Eczema, Psoriasis, Cutaneous Infections, Acne, and Other Common Skin Disorders


InternalMed_Harrison

InternalMed_Harrison. PART 2 Cardinal Manifestations and Presentation of Diseases some infections, most often those inappropriately treated with midto high-potency topical glucocorticoids. Involvement of the groin (tinea cruris) is more common in males than in females. It presents as a scaling, erythematous eruption sparing the scrotum. Infection of the foot (tinea pedis) is the most common dermatophyte infection and is often chronic; it is characterized by variable erythema, edema, scaling, pruritus, and occasionally vesiculation. The infection may be widespread or localized but generally involves the web space between the fourth and fifth toes. Infection of the nails (tinea unguium or onychomycosis) occurs in many patients with tinea pedis and is characterized by opacified, thickened nails and subungual debris. The distal-lateral variant is most common. Proximal subungual onychomycosis may be a marker for HIV infection or other immunocompromised states. Dermatophyte infection of the scalp (tinea capitis)


InternalMed_Harrison

InternalMed_Harrison. The distal-lateral variant is most common. Proximal subungual onychomycosis may be a marker for HIV infection or other immunocompromised states. Dermatophyte infection of the scalp (tinea capitis) continues to be common, particularly affecting inner-city children but also affecting adults. The predominant organism is Trichophyton tonsurans, which can produce a relatively noninflammatory infection with mild scale and hair loss that is diffuse or localized. T. tonsurans can also cause a markedly inflammatory dermatosis with edema and nodules. This latter presentation is a kerion.


InternalMed_Harrison

InternalMed_Harrison. The diagnosis of tinea can be made from skin scrapings, nail scrapings, or hair by culture or direct microscopic examination with potassium hydroxide (KOH). Nail clippings may be sent for histologic examination with periodic acid–Schiff (PAS) stain.


InternalMed_Harrison

InternalMed_Harrison. Both topical and systemic therapies may be used in dermatophyte infections. Treatment depends on the site involved and the type of infection. Topical therapy is generally effective for uncomplicated tinea corporis, tinea cruris, and limited tinea pedis. Topical agents are not effective as monotherapy for tinea capitis or onychomycosis (see below). Topical imidazoles, triazoles, and allylamines may be effective therapies for dermatophyte infections, but nystatin is not active against dermatophytes. Topicals are generally applied twice daily, and treatment should continue for 1 week beyond clinical resolution of the infection. Tinea pedis often requires longer treatment courses and frequently relapses. Oral antifungal agents may be required for recalcitrant tinea pedis or tinea corporis.


InternalMed_Harrison

InternalMed_Harrison. Oral antifungal agents are required for dermatophyte infections involving the hair and nails and for other infections unresponsive to topical therapy. A fungal etiology should be confirmed by direct microscopic examination or by culture before oral antifungal agents are prescribed. All of the oral agents may cause hepatotoxicity. They should not be used in women who are pregnant or breast-feeding.


InternalMed_Harrison

InternalMed_Harrison. Griseofulvin is approved in the United States for dermatophyte infections involving the skin, hair, or nails. When griseofulvin is used, a daily dose of 500 mg microsized or 375 mg ultramicrosized, administered with a fatty meal, is adequate for most dermatophyte infections. Higher doses are required for some cases of tinea pedis and tinea capitis. Markedly inflammatory tinea capitis may result in scarring and hair loss, and systemic or topical glucocorticoids may be helpful in preventing these sequelae. The duration of griseofulvin therapy may be 2 weeks for uncomplicated tinea corporis, 8–12 weeks for tinea capitis, or as long as 6–18 months for nail infections. Due to high relapse rates, griseofulvin is seldom used for nail infections. Common side effects of griseofulvin include gastrointestinal distress, headache, and urticaria.


InternalMed_Harrison

InternalMed_Harrison. Oral itraconazole is approved for onychomycosis. Itraconazole is given with food as either continuous daily therapy (200 mg/d) or pulses (200 mg bid for 1 week per month). Fingernails require 2 months of continuous therapy or two pulses. Toenails require 3 months of continuous therapy or three pulses. Itraconazole has the potential for serious interactions with other drugs requiring the P450 enzyme system for metabolism. Itraconazole should not be administered to patients with evidence of ventricular dysfunction or patients with known CHF. Terbinafine (250 mg/d) is also effective for onychomycosis, and the granule version is approved for treatment of tinea capitis. Therapy with terbinafine is continued for 6 weeks for fingernail and scalp infections and 12 weeks for toenail infections. Terbinafine has fewer interactions with other drugs than itraconazole, but caution should be used with patients who are on multiple medications. The risk/benefit ratio should be considered when an


InternalMed_Harrison

InternalMed_Harrison. Terbinafine has fewer interactions with other drugs than itraconazole, but caution should be used with patients who are on multiple medications. The risk/benefit ratio should be considered when an asymptomatic toenail infection is treated with systemic agents.


InternalMed_Harrison

InternalMed_Harrison. Tinea versicolor is caused by a nondermatophytic, dimorphic fungus, Malassezia furfur, a normal inhabitant of the skin. The expression of infection is promoted by heat and humidity. The typical lesions consist of oval scaly macules, papules, and patches concentrated on the chest, shoulders, and back but only rarely on the face or distal extremities. On dark skin the lesions often appear as hypopigmented areas, while on light skin they are slightly erythematous or hyperpigmented. A KOH preparation from scaling lesions will demonstrate a confluence of short hyphae and round spores (“spaghetti and meatballs”). Lotions or shampoos containing sulfur, salicylic acid, or selenium sulfide will clear the infection if used daily for 1–2 weeks and then weekly thereafter. These preparations are irritating if left on the skin for >10 min; thus, they should be washed off completely. Treatment with some oral antifungal agents is also effective, but they do not provide lasting results and are not FDA


InternalMed_Harrison

InternalMed_Harrison. if left on the skin for >10 min; thus, they should be washed off completely. Treatment with some oral antifungal agents is also effective, but they do not provide lasting results and are not FDA approved for this indication. A very short course of ketoconazole has been used, as have itraconazole and fluconazole. The patient must sweat after taking the medication if it is to be effective. Griseofulvin is not effective and terbinafine is not reliably effective for tinea versicolor.


InternalMed_Harrison

InternalMed_Harrison. Candidiasis is a fungal infection caused by a related group of yeasts whose manifestations may be localized to the skin and mucous membranes or, rarely, may be systemic and life-threatening (Chap. 240). The causative organism is usually Candida albicans. These organisms are normal saprophytic inhabitants of the gastrointestinal tract but may overgrow due to broad-spectrum antibiotic therapy, diabetes mellitus, or immunosuppression and cause disease. Candidiasis is a oral cavity is commonly involved. Lesions may occur on the tongue or very common infection in HIV-infected individuals (Chap. 226). The buccal mucosa (thrush) and appear as white plaques. Fissured, macerated lesions at the corners of the mouth (perléche) are often seen in individuals with poorly fitting dentures and may also be associated with candidal infection. In addition, candidal infections have an affinity for sites that are chronically wet and macerated, including the skin around nails (onycholysis and paronychia),


InternalMed_Harrison

InternalMed_Harrison. associated with candidal infection. In addition, candidal infections have an affinity for sites that are chronically wet and macerated, including the skin around nails (onycholysis and paronychia), and in intertriginous areas. Intertriginous lesions are characteristically edematous, erythematous, and scaly, with scattered “satellite pustules.” In males, there is often involvement of the penis and scrotum as well as the inner aspect of the thighs. In contrast to dermatophyte infections, candidal infections are frequently painful and accompanied by a marked inflammatory response. Diagnosis of candidal infection is based upon the clinical pattern and demonstration of yeast on KOH preparation or culture.


InternalMed_Harrison

InternalMed_Harrison. Treatment involves removal of any predisposing factors such as antibiotic therapy or chronic wetness and the use of appropriate topical or systemic antifungal agents. Effective topicals include nystatin or azoles (miconazole, clotrimazole, econazole, or ketoconazole). The associated inflammatory response accompanying candidal infection on glabrous skin can be treated with a mild glucocorticoid lotion or cream (2.5% hydrocortisone). Systemic therapy is usually reserved for immunosuppressed patients or individuals with chronic or recurrent disease who fail to respond to appropriate topical therapy. Oral agents approved for the treatment of candidiasis include itraconazole and fluconazole. Oral nystatin is effective only for candidiasis of the gastrointestinal tract. Griseofulvin and terbinafine are not effective.


InternalMed_Harrison

InternalMed_Harrison. Warts are cutaneous neoplasms caused by papillomaviruses. More than 100 different human papillomaviruses (HPVs) have been described. A typical wart, verruca vulgaris, is sessile, dome-shaped, and usually about a centimeter in diameter. Its surface is hyperkeratotic, consisting of many small filamentous projections. The HPV types that cause typical verruca vulgaris also cause typical plantar warts, flat warts (verruca plana), and filiform warts. Plantar warts are endophytic and are covered by thick keratin. Paring of the wart will generally reveal a central core of keratinized debris and punctate bleeding points. Filiform warts are most commonly seen on the face, neck, and skinfolds and present as papillomatous lesions on a narrow base. Flat warts are only slightly elevated and have a velvety, nonverrucous surface. They have a propensity for the face, arms, and legs and are often spread by shaving.


InternalMed_Harrison

InternalMed_Harrison. Genital warts begin as small papillomas that may grow to form large, fungating lesions. In women, they may involve the labia, perineum, or perianal skin. In addition, the mucosa of the vagina, urethra, and anus can be involved as well as the cervical epithelium. In men, the lesions often occur initially in the coronal sulcus but may be seen on the shaft of the penis, the scrotum, or the perianal skin or in the urethra.


InternalMed_Harrison

InternalMed_Harrison. Appreciable evidence has accumulated indicating that HPV plays a role in the development of neoplasia of the uterine cervix and anogenital skin (Chap. 117). HPV types 16 and 18 have been most intensely studied and are the major risk factors for intraepithelial neoplasia and squamous cell carcinoma of the cervix, anus, vulva, and penis. The risk is higher among patients immunosuppressed after solid organ transplantation and among those infected with HIV. Recent evidence also implicates other HPV types. Histologic examination of biopsied samples from affected sites may reveal changes associated with typical warts and/or features typical of intraepidermal carcinoma (Bowen’s disease). Squamous cell carcinomas associated with HPV infections have also been observed in extragenital skin (Chap. 105), most commonly in patients immunosuppressed after organ transplantation. Patients on long-term immunosuppression should be monitored for the development of squamous cell carcinoma and other


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InternalMed_Harrison. 105), most commonly in patients immunosuppressed after organ transplantation. Patients on long-term immunosuppression should be monitored for the development of squamous cell carcinoma and other cutaneous malignancies.


InternalMed_Harrison

InternalMed_Harrison. Treatment of warts, other than anogenital warts, should be tempered by the observation that a majority of warts in normal individuals resolve spontaneously within 1–2 years. There are many modalities available to treat warts, but no single therapy is universally effective. Factors that influence the choice of therapy include the location of the wart, the extent of disease, the age and immunologic status of the patient, and the patient’s desire for therapy. Perhaps the most useful and convenient method for treating warts in almost any location is cryotherapy with liquid nitrogen. Equally effective for nongenital warts, but requiring much more patient compliance, is the use of keratolytic agents such as salicylic acid plasters or solutions. For genital warts, in-office application of a podophyllin solution is moderately effective but may be associated with marked local reactions. Prescription preparations of dilute, purified podophyllin are available for home use. Topical imiquimod, a


InternalMed_Harrison

InternalMed_Harrison. solution is moderately effective but may be associated with marked local reactions. Prescription preparations of dilute, purified podophyllin are available for home use. Topical imiquimod, a potent inducer of local cytokine release, has been approved for treatment of genital warts. A new topical compound composed of green tea extracts (sinecatechins) is also available. Conventional and laser surgical procedures may be required for recalcitrant warts. Recurrence of warts appears to be common to all these modalities. A highly effective vaccine for selected types of HPV has been approved by the FDA, and its use appears to reduce the incidence of anogenital and cervical carcinoma.


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InternalMed_Harrison. See Chap. 216. See Chap. 217. Acne vulgaris is a self-limited disorder primarily of teenagers and young adults, although perhaps 10–20% of adults may continue to experience some form of the disorder. The permissive factor for the expression of the disease in adolescence is the increase in sebum production by sebaceous glands after puberty. Small cysts, called comedones, form in hair follicles due to blockage of the follicular orifice by retention of keratinous material and sebum. The activity of bacteria (Propionibacterium acnes) within the comedones releases free fatty acids from sebum, causes inflammation within the cyst, and results in rupture of the cyst wall. An inflammatory foreign-body reaction develops as result of extrusion of oily and keratinous debris from the cyst.


InternalMed_Harrison

InternalMed_Harrison. The clinical hallmark of acne vulgaris is the comedone, which may be closed (whitehead) or open (blackhead). Closed comedones appear as 1to 2-mm pebbly white papules, which are accentuated when the skin is stretched. They are the precursors of inflammatory lesions of acne vulgaris. The contents of closed comedones are not easily expressed. Open comedones, which rarely result in inflammatory acne lesions, have a large dilated follicular orifice and are filled with easily expressible oxidized, darkened, oily debris. Comedones are usually accompanied by inflammatory lesions: papules, pustules, or nodules.


InternalMed_Harrison

InternalMed_Harrison. The earliest lesions seen in adolescence are generally mildly inflamed or noninflammatory comedones on the forehead. Subsequently, more typical inflammatory lesions develop on the cheeks, nose, and chin (Fig. 71-7). The most common location for acne is the face, but involvement of the chest and back is common. Most disease remains mild and does not lead to scarring. A small number of patients develop large inflammatory cysts and nodules, which may drain and result in significant scarring. Regardless of the severity, acne may affect a patient’s quality of life. With adequate treatment, this effect may be transient. In the case of severe, scarring acne, the effects can be permanent and profound. Early therapeutic intervention in severe acne is essential. Exogenous and endogenous factors can alter the expression of acne vulgaris. Friction and trauma (from headbands or chin straps of athletic helmets), application of comedogenic topical agents (cosmetics


InternalMed_Harrison

InternalMed_Harrison. CHAPTER 71 Eczema, Psoriasis, Cutaneous Infections, Acne, and Other Common Skin Disorders PART 2 Cardinal Manifestations and Presentation of Diseases FIguRE 71-7 Acne vulgaris. An example of acne vulgaris with inflammatory papules, pustules, and comedones. (Courtesy of Kalman Watsky, MD; with permission.) or hair preparations), or chronic topical exposure to certain industrial compounds may elicit or aggravate acne. Glucocorticoids, topical or systemic, may also elicit acne. Other systemic medications such as oral contraceptive pills, lithium, isoniazid, androgenic steroids, halogens, phenytoin, and phenobarbital may produce acneiform eruptions or aggravate preexisting acne. Genetic factors and polycystic ovary disease may also play a role.


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InternalMed_Harrison. Treatment of acne vulgaris is directed toward elimination of comedones by normalizing follicular keratinization, decreasing sebaceous gland activity, decreasing the population of P. acnes, and decreasing inflammation. Minimal to moderate pauci-inflammatory disease may respond adequately to local therapy alone. Although areas affected with acne should be kept clean, overly vigorous scrubbing may aggravate acne due to mechanical rupture of comedones. Topical agents such as retinoic acid, benzoyl peroxide, or salicylic acid may alter the pattern of epidermal desquamation, preventing the formation of comedones and aiding in the resolution of preexisting cysts. Topical antibacterial agents (such as azelaic acid, erythromycin, clindamycin, or dapsone) are also useful adjuncts to therapy.


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InternalMed_Harrison. Patients with moderate to severe acne with a prominent inflammatory component will benefit from the addition of systemic therapy, such as tetracycline in doses of 250–500 mg bid or doxycycline in doses of 100 mg bid. Minocycline is also useful. Such antibiotics appear to have anti-inflammatory effects independent of their antibacterial effects. Female patients who do not respond to oral antibiotics may benefit from hormonal therapy. Several oral contraceptives are now approved by the FDA for use in the treatment of acne vulgaris.


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InternalMed_Harrison. Patients with severe nodulocystic acne unresponsive to the therapies discussed above may benefit from treatment with the synthetic retinoid isotretinoin. Its dose is based on the patient’s weight, and it is given once daily for 5 months. Results are excellent in appropriately selected patients. Its use is highly regulated due to its potential for severe adverse events, primarily teratogenicity and depression. In addition, patients receiving this medication develop extremely dry skin and cheilitis and must be followed for development of hypertriglyceridemia.


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InternalMed_Harrison. At present, prescribers must enroll in a program designed to prevent pregnancy and adverse events while patients are taking isotretinoin. These measures are imposed to ensure that all prescribers are familiar with the risks of isotretinoin; that all female patients have two negative pregnancy tests prior to initiation of therapy and a negative pregnancy test prior to each refill; and that all patients have been warned about the risks associated with isotretinoin. FIguRE 71-8 Acne rosacea. Prominent facial erythema, telangiecta-sia, scattered papules, and small pustules are seen in this patient with acne rosacea. (Courtesy of Robert Swerlick, MD; with permission.)


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InternalMed_Harrison. Acne rosacea, commonly referred to simply as rosacea, is an inflammatory disorder predominantly affecting the central face. Persons most often affected are Caucasians of northern European background, but rosacea also occurs in patients with dark skin. Rosacea is seen almost exclusively in adults, only rarely affecting patients <30 years old. Rosacea is more common in women, but those most severely affected are men. It is characterized by the presence of erythema, telangiectases, and superficial pustules (Fig. 71-8) but is not associated with the presence of comedones. Rosacea rarely involves the chest or back.


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InternalMed_Harrison. There is a relationship between the tendency for facial flushing and the subsequent development of acne rosacea. Often, individuals with rosacea initially demonstrate a pronounced flushing reaction. This may be in response to heat, emotional stimuli, alcohol, hot drinks, or spicy foods. As the disease progresses, the flush persists longer and longer and may eventually become permanent. Papules, pustules, and telangiectases can become superimposed on the persistent flush. Rosacea of very long standing may lead to connective tissue overgrowth, particularly of the nose (rhinophyma). Rosacea may also be complicated by various inflammatory disorders of the eye, including keratitis, blepharitis, iritis, and recurrent chalazion. These ocular problems are potentially sight-threatening and warrant ophthalmologic evaluation.


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InternalMed_Harrison. Acne rosacea can be treated topically or systemically. Mild disease often responds to topical metronidazole, sodium sulfacetamide, or azaleic acid. More severe disease requires oral tetracyclines: tetracycline, 250–500 mg bid; doxycycline, 100 mg bid; or minocycline, 50–100 mg bid. Residual telangiectasia may respond to laser therapy. Topical glucocorticoids, especially potent agents, should be avoided because chronic use of these preparations may elicit rosacea. Application of topical agents to the skin is not effective treatment for ocular disease.


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InternalMed_Harrison. Although smallpox vaccinations were discontinued several decades ago for the general population, they are still required for certain military personnel and first responders. In the absence of a bioterrorism attack and a real or potential exposure to smallpox, such vaccination is contraindicated in persons with a history of skin diseases such as AD, eczema, and psoriasis, who have a higher incidence of adverse events associated with smallpox vaccination. In the case of such exposure, the risk of smallpox infection outweighs the risk of adverse events from the vaccine (Chap. 261e).


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InternalMed_Harrison. Skin Manifestations of internal Disease Jean L. Bolognia, Irwin M. Braverman It is a generally accepted concept in medicine that the skin can develop signs of internal disease. Therefore, in textbooks of medicine, one finds a chapter describing in detail the major systemic disorders that 72 can be identified by cutaneous signs. The underlying assumption of such a chapter is that the clinician has been able to identify the specific disorder in the patient and needs only to read about it in the textbook. In reality, concise differential diagnoses and the identification of these disorders are actually difficult for the nondermatologist because he or she is not well-versed in the recognition of cutaneous lesions or their spectrum of presentations. Therefore, this chapter covers this particular topic of cutaneous medicine not by simply focusing on individual diseases, but by describing the various presenting clinical signs and symptoms that point to specific disorders. Concise differential


InternalMed_Harrison

InternalMed_Harrison. topic of cutaneous medicine not by simply focusing on individual diseases, but by describing the various presenting clinical signs and symptoms that point to specific disorders. Concise differential diagnoses will be generated in which the significant diseases will be distinguished from the more common cutaneous disorders that have minimal or no significance with regard to associated internal disease. The latter disorders are reviewed in table form and always need to be excluded when considering the former. For a detailed description of individual diseases, the reader should consult a dermatologic text.


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InternalMed_Harrison. (Table 72-1) When an eruption is characterized by elevated lesions, either papules (<1 cm) or plaques (>1 cm), in association with scale, it is referred to as papulosquamous. The most common papulosquamous diseases—tinea, psoriasis, pityriasis rosea, and lichen planus—are primary cutaneous disorders (Chap. 71). When psoriatic lesions are accompanied by arthritis, the possibility of psoriatic arthritis or reactive arthritis (formerly known as Reiter’s syndrome) should be considered. A history of oral ulcers, conjunctivitis, uveitis, and/or urethritis points to the latter diagnosis. Lithium, beta blockers, HIV or streptococcal infections, and a rapid taper of systemic glucocorticoids are known to exacerbate psoriasis. Comorbidities in patients with psoriasis include cardiovascular disease and metabolic syndrome.


InternalMed_Harrison

InternalMed_Harrison. Whenever the diagnosis of pityriasis rosea or lichen planus is made, it is important to review the patient’s medications because the eruption may resolve by simply discontinuing the offending agent. Pityriasis rosea–like drug eruptions are seen most commonly with beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and metronidazole, whereas the drugs that can produce a lichenoid eruption include thiazides, antimalarials, quinidine, beta blockers, and ACE inhibitors. In some populations, there is a higher prevalence of hepatitis C viral infection in patients with lichen planus. Lichen planus–like lesions are also observed in chronic graft-versus-host disease.


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InternalMed_Harrison. In its early stages, the mycosis fungoides (MF) form of cutaneous T cell lymphoma (CTCL) may be confused with eczema or psoriasis, but it often fails to respond to the appropriate therapy for those inflammatory diseases. MF can develop within lesions of large-plaque parapsoriasis and is suggested by an increase in the thickness of the lesions. The diagnosis of MF is established by skin biopsy in which collections of atypical T lymphocytes are found in the epidermis and dermis. As the disease progresses, cutaneous tumors and lymph node involvement may appear.


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InternalMed_Harrison. In secondary syphilis, there are scattered red-brown papules with thin scale. The eruption often involves the palms and soles and can resemble pityriasis rosea. Associated findings are helpful in making the diagnosis and include annular plaques on the face, nonscarring alopecia, condyloma lata (broad-based and moist), and mucous patches as well as lymphadenopathy, malaise, fever, headache, and myalgias. The interval between the primary chancre and the secondary stage is usually 4–8 weeks, and spontaneous resolution without appropriate therapy occurs. SELECTED CAuSES of PAPuLoSquAMouS SKin LESionS 1. Primary cutaneous disorders a. b. c. d. e. Parapsoriasis, small plaque and large plaque f. 2. 3. a. Lupus erythematosus, primarily subacute or chronic (discoid) lesionsc b. Cutaneous T cell lymphoma, in particular, mycosis fungoidesd c. d. Reactive arthritis (formerly known as Reiter's syndrome) e.


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InternalMed_Harrison. aDiscussed in detail in Chap. 71; cardiovascular disease and the metabolic syndrome are comorbidities in psoriasis; primarily in Europe, hepatitis C virus is associated with oral lichen planus. bAssociated with chronic sun exposure more often than exposure to arsenic; usually one or a few lesions. cSee also Red Lesions in “Papulonodular Skin Lesions.” dAlso cutaneous lesions of HTLV-1-associated adult T cell leukemia/lymphoma. eSee also Red-Brown Lesions in “Papulonodular Skin Lesions.” (Table 72-2) Erythroderma is the term used when the majority of the skin surface is erythematous (red in color). There may be associated scale, erosions, or pustules as well as shedding of the hair and nails. Potential systemic manifestations include fever, chills, hypothermia, reactive lymphadenopathy, peripheral edema, hypoalbuminemia, and high-output cardiac failure. The major etiologies of erythroderma are (1) cutaneous diseases such as psoriasis and dermatitis (Table 72-3); (2) drugs; (3) systemic


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InternalMed_Harrison. edema, hypoalbuminemia, and high-output cardiac failure. The major etiologies of erythroderma are (1) cutaneous diseases such as psoriasis and dermatitis (Table 72-3); (2) drugs; (3) systemic diseases, most commonly CTCL; and (4) idiopathic. In the first three groups, the location and description of the initial lesions, prior to the development of the erythroderma, aid in the diagnosis. For example, a history of red scaly plaques on the elbows and knees would point to psoriasis. It is also important to examine the skin carefully for a migration of the erythema and associated secondary changes such as pustules or erosions. Migratory waves of erythema studded with superficial pustules are seen in pustular psoriasis.


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InternalMed_Harrison. Drug-induced erythroderma (exfoliative dermatitis) may begin as an exanthematous (morbilliform) eruption (Chap. 74) or may arise as diffuse erythema. A number of drugs can produce an erythroderma, including penicillins, sulfonamides, carbamazepine, phenytoin, and allopurinol. Fever and peripheral eosinophilia often accompany the eruption, and there may also be facial swelling, hepatitis, myocarditis, thyroiditis, and allergic interstitial nephritis; this constellation is frequently referred to as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity reaction (DIHS). In addition, these reactions, especially to aromatic anticonvulsants, can lead to a pseudolymphoma syndrome (with adenopathy and CAuSES of ERyTHRoDERMA 1. Primary cutaneous disorders a. b. c. 2. 3. a. Cutaneous T cell lymphoma (Sézary syndrome, erythrodermic mycosis fungoides) b. 4. Idiopathic (usually older men) a Discussed in detail in Chap. 71.


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InternalMed_Harrison. b. c. 2. 3. a. Cutaneous T cell lymphoma (Sézary syndrome, erythrodermic mycosis fungoides) b. 4. Idiopathic (usually older men) a Discussed in detail in Chap. 71. CHAPTER 72 Skin Manifestations of Internal Disease PART 2 Cardinal Manifestations and Presentation of Diseases Abbreviations: Ab, antibody; HSV, herpes simplex virus; IL, interleukin; IM, intramuscular; IV, intravenous; MTX, methotrexate; PUVA, psoralens + ultraviolet A irradiation; SAPHO, synovitis, acne, pustulosis, hyperostosis, and osteitis (also referred to as chronic recurrent multifocal osteomyelitis); TNF, tumor necrosis factor; UV-A, ultraviolet A irradiation; UV-B, ultraviolet B irradiation. circulating atypical lymphocytes), while reactions to allopurinol may The most common causes of nonscarring alopecia include androgebe accompanied by gastrointestinal bleeding. netic alopecia, telogen effluvium, alopecia areata, tinea capitis, and the


InternalMed_Harrison

InternalMed_Harrison. The most common malignancy that is associated with erythroderma early phase of traumatic alopecia (Table 72-5). In women with androis CTCL; in some series, up to 25% of the cases of erythroderma were genetic alopecia, an elevation in circulating levels of androgens may be due to CTCL. The patient may progress from isolated plaques and seen as a result of ovarian or adrenal gland dysfunction or neoplasm. tumors, but more commonly, the erythroderma is present throughout When there are signs of virilization, such as a deepened voice and the course of the disease (Sézary syndrome). In the Sézary syndrome, enlarged clitoris, the possibility of an ovarian or adrenal gland tumor there are circulating clonal atypical T lymphocytes, pruritus, and lymph-should be considered. adenopathy. In cases of erythroderma where there is no apparent cause Exposure to various drugs can also cause diffuse hair loss, (idiopathic), longitudinal evaluation is mandatory to monitor for the usually by inducing a


InternalMed_Harrison

InternalMed_Harrison. erythroderma where there is no apparent cause Exposure to various drugs can also cause diffuse hair loss, (idiopathic), longitudinal evaluation is mandatory to monitor for the usually by inducing a telogen effluvium. An exception is the anagen possible development of CTCL. There have been isolated case reports effluvium observed with antimitotic agents such as daunorubicin. of erythroderma secondary to some solid tumors—lung, liver, prostate, Alopecia is a side effect of the following drugs: warfarin, heparin, thyroid, and colon—but it is primarily during a late stage of the disease. propylthiouracil, carbimazole, isotretinoin, acitretin, lithium, beta blockers, interferons, colchicine, and amphetamines. Fortunately, spontaneous regrowth usually follows discontinuation of the offend- ing agent. (Table 72-4) The two major forms of alopecia are scarring and non-Less commonly, nonscarring alopecia is associated with lupus eryscarring. Scarring alopecia is associated with fibrosis,


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InternalMed_Harrison. ing agent. (Table 72-4) The two major forms of alopecia are scarring and non-Less commonly, nonscarring alopecia is associated with lupus eryscarring. Scarring alopecia is associated with fibrosis, inflammation, thematosus and secondary syphilis. In systemic lupus there are two and loss of hair follicles. A smooth scalp with a decreased number of forms of alopecia—one is scarring secondary to discoid lesions (see follicular openings is usually observed clinically, but in some patients, below), and the other is nonscarring. The latter form coincides with the changes are seen only in biopsy specimens from affected areas. In flares of systemic disease and may involve the entire scalp or just nonscarring alopecia, the hair shafts are absent or miniaturized, but the the frontal scalp, with the appearance of multiple short hairs (“lupus hair follicles are preserved, explaining the reversible nature of nonscar-hairs”) as a sign of initial regrowth. Scattered, poorly circumscribed ring


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InternalMed_Harrison. the appearance of multiple short hairs (“lupus hair follicles are preserved, explaining the reversible nature of nonscar-hairs”) as a sign of initial regrowth. Scattered, poorly circumscribed ring alopecia. patches of alopecia with a “moth-eaten” appearance are a manifestation


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InternalMed_Harrison. CAuSES of ALoPECiA I. Nonscarring alopecia A. Primary cutaneous disorders 1. 2. 3. 4. 5. B. Drugs C. Systemic diseases 1. 2. 3. 4. 5. 6. Deficiencies of protein, biotin, zinc, and perhaps iron II. A. 1. 2. 3. 4. 5. B. Systemic diseases 1. Discoid lesions in the setting of systemic lupus erythematosusb 2. 3. a Most patients with trichotillomania, pressure-induced alopecia, or early stages of traction alopecia. b While the majority of patients with discoid lesions have only cutaneous disease, these lesions do represent one of the 11 American College of Rheumatology criteria (1982) for systemic lupus erythematosus. c Can involve underlying muscles and osseous structures. of the secondary stage of syphilis. Diffuse thinning of the hair is also 355 associated with hypothyroidism and hyperthyroidism (Table 72-4).


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InternalMed_Harrison. of the secondary stage of syphilis. Diffuse thinning of the hair is also 355 associated with hypothyroidism and hyperthyroidism (Table 72-4). Scarring alopecia is more frequently the result of a primary cutaneous disorder such as lichen planus, folliculitis decalvans, chronic cutaneous (discoid) lupus, or linear scleroderma (morphea) than it is a sign of systemic disease. Although the scarring lesions of discoid lupus can be seen in patients with systemic lupus, in the majority of patients, the disease process is limited to the skin. Less common causes of scarring alopecia include sarcoidosis (see “Papulonodular Skin Lesions,” below) and cutaneous metastases.


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InternalMed_Harrison. In the early phases of discoid lupus, lichen planus, and folliculitis decalvans, there are circumscribed areas of alopecia. Fibrosis and subsequent loss of hair follicles are observed primarily in the center of these alopecic patches, whereas the inflammatory process is most prominent at the periphery. The areas of active inflammation in discoid lupus are erythematous with scale, whereas the areas of previous inflammation are often hypopigmented with a rim of hyperpigmentation. In lichen planus, perifollicular macules at the periphery are usually violet-colored. A complete examination of the skin and oral mucosa combined with a biopsy and direct immunofluorescence microscopy of inflamed skin will aid in distinguishing these two entities. The peripheral active lesions in folliculitis decalvans are follicular pustules; these patients can develop a reactive arthritis.


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InternalMed_Harrison. (Table 72-6) In figurate eruptions, the lesions form rings and arcs that are usually erythematous but can be skin-colored to brown. Most commonly, they are due to primary cutaneous diseases such as tinea, urticaria, granuloma annulare, and erythema annulare centrifugum (Chaps. 71 and 73). An underlying systemic illness is found in a second, less common group of migratory annular erythemas. It includes erythema migrans, erythema gyratum repens, erythema marginatum, and necrolytic migratory erythema. In erythema gyratum repens, one sees numerous mobile concentric arcs and wavefronts that resemble the grain in wood. A search for an CHAPTER 72 Skin Manifestations of Internal Disease Diffuse shedding of normal hairs Follows major stress (high fever, severe infection) or change in hormone levels (postpartum) Miniaturization of hairs along the midline of the scalp Recession of the anterior scalp line in men and some women


InternalMed_Harrison

InternalMed_Harrison. Miniaturization of hairs along the midline of the scalp Recession of the anterior scalp line in men and some women Well-circumscribed, circular areas of hair loss, 2–5 cm in diameter In extensive cases, coalescence of lesions and/or involvement of other hair-bearing surfaces of the body Pitting or sandpapered appearance of the nails Varies from scaling with minimal hair loss to discrete patches with “black dots” (broken infected hairs) to boggy plaque with pustules (kerion)b Broken hairs, often of varying lengths Irregular outline Stress causes more of the asynchronous growth cycles of individual hairs to become synchronous; therefore, larger numbers of growing (anagen) hairs simultaneously enter the dying (telogen) phase Increased sensitivity of affected hairs to the effects of androgens Increased levels of circulating androgens (ovarian or adrenal source in women) The germinative zones of the hair follicles are surrounded by T lymphocytes


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InternalMed_Harrison. Increased levels of circulating androgens (ovarian or adrenal source in women) The germinative zones of the hair follicles are surrounded by T lymphocytes Occasional associated diseases: hyperthyroidism, hypothyroidism, vitiligo, Down syndrome Invasion of hairs by dermatophytes, most commonly Trichophyton tonsurans Traction with curlers, rubber bands, braiding Exposure to heat or chemicals (e.g., hair straighteners) Mechanical pulling (trichotillomania) Observation; discontinue any drugs that have alopecia as a side effect; must exclude underlying metabolic causes, e.g., hypothyroidism, hyperthyroidism If no evidence of hyperandrogenemia, then topical minoxidil; finasteridea; spironolactone (women); hair transplant Oral griseofulvin or terbinafine plus 2.5% selenium sulfide or ketoconazole shampoo; examine family members


InternalMed_Harrison

InternalMed_Harrison. Oral griseofulvin or terbinafine plus 2.5% selenium sulfide or ketoconazole shampoo; examine family members Discontinuation of offending hair style or chemical treatments; diagnosis of trichotillomania may require observation of shaved hairs (for growth) or biopsy, possibly followed by psychotherapy aTo date, Food and Drug Administration–approved for men. bScarring alopecia can occur at sites of kerions. cMay also be scarring, especially late-stage traction alopecia. CAuSES of figuRATE SKin LESionS I. Primary cutaneous disorders A. Tinea B. Urticaria (primary in ≥90% of patients) C. Granuloma annulare D. Erythema annulare centrifugum E. Psoriasis II. A. 1. Erythema migrans (CDC case definition is ≥5 cm in diameter) 2. Urticaria (≤10% of patients) 3. 4. 5. 6. B. Nonmigratory 1. 2. 3. 4. Cutaneous T cell lymphoma (especially mycosis fungoides) aMigratory erythema with erosions; favors lower extremities and girdle area.


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InternalMed_Harrison. 4. 5. 6. B. Nonmigratory 1. 2. 3. 4. Cutaneous T cell lymphoma (especially mycosis fungoides) aMigratory erythema with erosions; favors lower extremities and girdle area. Abbreviation: CDC, Centers for Disease Control and Prevention. underlying malignancy is mandatory in a patient with this eruption. Erythema migrans is the cutaneous manifestation of Lyme disease, which is caused by the spirochete Borrelia burgdorferi. In the initial stage (3–30 days after tick bite), a single annular lesion is usually seen, which can expand to ≥10 cm in diameter. Within several days, up to half of the patients develop multiple smaller erythematous lesions at sites distant from the bite. Associated symptoms include fever, headache, photophobia, myalgias, arthralgias, and malar rash. Erythema marginatum is seen in patients with rheumatic fever, primarily on the trunk. Lesions are pink-red in color, flat to minimally elevated, and transient.


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InternalMed_Harrison. There are additional cutaneous diseases that present as annular eruptions but lack an obvious migratory component. Examples include CTCL, subacute cutaneous lupus, secondary syphilis, and sarcoidosis (see “Papulonodular Skin Lesions,” below). (Table 72-7) In addition to acne vulgaris and acne rosacea, the two major forms of acne (Chap. 71), there are drugs and systemic diseases that can lead to acneiform eruptions. Patients with the carcinoid syndrome have episodes of flushing of the head, neck, and sometimes the trunk. Resultant skin changes of the face, in particular telangiectasias, may mimic the clinical appearance of acne rosacea. CAuSES of ACnEifoRM ERuPTionS I. Primary cutaneous disorders A. Acne vulgaris B. Acne rosacea II. Drugs, e.g., anabolic steroids, glucocorticoids, lithium, EGFRa inhibitors, iodides III. A. 1. Adrenal origin, e.g., Cushing’s disease, 21-hydroxylase deficiency 2. Ovarian origin, e.g., polycystic ovary syndrome, ovarian hyperthecosis


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InternalMed_Harrison. III. A. 1. Adrenal origin, e.g., Cushing’s disease, 21-hydroxylase deficiency 2. Ovarian origin, e.g., polycystic ovary syndrome, ovarian hyperthecosis B. Cryptococcosis, disseminated C. Dimorphic fungal infections D. Behçet’s disease aEGFR, epidermal growth factor receptor. PART 2 Cardinal Manifestations and Presentation of Diseases


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InternalMed_Harrison. Acneiform eruptions (see “Acne,” above) and folliculitis represent the most common pustular dermatoses. An important consideration in the evaluation of follicular pustules is a determination of the associated pathogen, e.g., normal flora, Staphylococcus aureus, Pseudomonas aeruginosa (“hot tub” folliculitis), Malassezia, dermatophytes (Majocchi’s granuloma), and Demodex spp. Noninfectious forms of folliculitis include HIVor immunosuppression-associated eosinophilic folliculitis and folliculitis secondary to drugs such as glucocorticoids, lithium, and epidermal growth factor receptor (EGFR) inhibitors. Administration of high-dose systemic glucocorticoids can result in a widespread eruption of follicular pustules on the trunk, characterized by lesions in the same stage of development. With regard to underlying systemic diseases, nonfollicular-based pustules are a characteristic component of pustular psoriasis (sterile) and can be seen in septic emboli of bacterial or fungal origin (see