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Common Superficial Fungal Infections in Patients with AIDS Raza Aly and Timothy Berger

From the Department of Dermatology, University of California San Francisco, San Francisco, California

Superficial mycotic infections such as seborrheic dermatitis, tinea pedis, tinea corporis, and onychomycosis are common in patients infected with human immunodeficiency virus (HIV). In communities where HIV infections are frequent, some of these clinical presentations serve as markers of the stage of HIV infection. The diagnosis of superficial fungal infection in HIV-positive patients may be difficult because of atypical clinical manifestations. Therefore, to ensure a correct diagnosis, skin scrapings should be collected for potassium hydroxide preparations and cultures. Most forms of dermatophytosis in HIV-positive patients respond well to many topical antifungal agents, such as azoles, terbinafine, and ciclopirox olamine. If the disease is chronic and extensive, then ketoconazole, fluconazole, and itraconazole are each effective.

Various skin conditions are associated with HIV infection. Epidemiologic studies have shown that almost all persons with HIV infection will have skin disorders at some point during their disease [1]. Dermatophytic infections are common in HIV-infected patients; however, these skin diseases may not occur any more frequently in HIV-positive patients than in comparable groups. Studies have been few and their results contrary. In one survey, for example, the prevalence of dermatophytosis was not significantly higher in a group of HIV-infected patients (37%) than in a paired population of HIV-negative homosexual males (32%). These investigators noted that the superficial infections were more common in both groups of homosexual males than in the general population [2]. In another study, however, the prevalence of dermatophytosis was four times higher among HIV-infected persons [3]. While cutaneous fungal infections in most patients with HIV infection follow a normal pattern, atypical forms are common in patients with AIDS. Most HIV-infected patients will have some form of oral candidiasis at some point during their disease [4]. Although oral candidiasis can occur at any stage of HIV infection, it is most common in patients with low CD4 cell counts.

Common Superficial Dermatomycoses (Infections Due to Nondermatophytes) Seborrheic dermatitis (SD) is the most common skin disorder in HIV-positive patients. The role of Malassezia furfur in causing SD is controversial and is based on the observation that this skin condition responds well to antifungal therapy. However,

Reprints or correspondence: Dr. Raza Aly, Department of Dennatology, Dennatology Research, AC-34, Box 0517, University of California San Francisco, San Francisco, California 94143-0517. Clinical Infectious Diseases

1996;22(SuppI2):S128-32

© 1996 by The University of Chicago. All rights reserved. 1058--4838/96/2205-0008$02.00

according to some investigators, M. furfur may be one of the causes of SD [5]. A summary of the etiologic status and treatment of various fungal infections is shown in table 1 [6, 7]. The efficacy of antifungal therapy is paralleled by a reduction in the number of M. furfur organisms [8]. SD is often observed in patients in the early stage of HIV infection. SD is one of the earliest clinical markers of HIV infection; its prevalence is up to 80% among patients with AIDS [5]. A correlation seems to exist between the appearance of certain diseases and the CD4 cell count (table 2). In patients with HIV infection, SD is often more explosive, inflammatory, and severe than that usually seen in otherwise healthy patients [9]. The onset of SD in patients with HIV infection may often be rapid, and the rash can be extensive [10]. Involvement of the groin is frequently noted in these patients. Ketoconazole shampoo and antifungal creams are used. Oral ketoconazole (250 mg/d for 7-14 days) is effective in controlling most refractory cases [11]. The use of topical steroids and then ketoconazole cream and antibacterial soaps is also beneficial [12].

Pityriasis Versicolor and Malassezia (Pityrosporum) Folliculitis These diseases arise from overgrowth of M. furfur. Although pityriasis versicolor has been seen in patients with HIV infection, it is not particularly common. The clinical features do not differ from those seen in cases involving non-HIV-infected patients. Pityriasis versicolor can be treated effectively with ketoconazole taken orally (400 mg as a single dose for 1-3 days, and then repeated monthly) or with topical selenium sulfide or ketoconazole shampoo. M furfur can also induce folliculitis in HIV-positive patients. Malassezia folliculitis responds to treatment with ketoconazole (200 mg/d for 10-14 days). Ketoconozole may interact with other drugs, such as rifampin and phenytoin, that often are used in the treatment of other diseases associated with AIDS.

eID 1996;22 (Suppl 2)

Table 1.

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Superficial Fungal Infection and AIDS

Etiologic status and treatment of superficial fungal skin infections. Therapy

Fungal etiology

Disease Pityriasis versicolor

Definite

Malassezia folliculitis Seborrheic dermatitis

Definite Controversial

Onychomycosis Dermatophytosis

Definite Definite

Cutaneous and oral candidiasis

Definite

Eosinophilic folliculitis

Unknown

Oral ketoconazole, topical selenium sulfide, or ketoconazole shampoo Oral ketoconazole Topical antifungal creams, ketoconazole shampoo, oral ketoconazole Fluconazole, itraconazole Topical antifungal creams (imidazoles or allylamine), oral griseofulvin, and oral imidazoles Nystatin tablet and oral suspension, clotrimazole troches, oral imidazoles Ultraviolet phototherapy, itraconazole, topical steroids

NOTE. Because HIV-positive patients are often achlorhydric, ingestion of cranberry juice or cola beverages is suggested to increase gastric acidity for better absorption of itraconazole and ketoconazole [6, 7].

Dermatophytosis (Infection Due to Dermatophytes) Tinea corporis, tinea cruris, tinea pedis, and onychomycosis all occur in patients with HIV infection. Tinea pedis, the most common type of dermatophytosis in patients with symptomatic HIV disease, is usually manifested by typical interdigital maceration with scaling and diffuse hyperkeratosis of the sole. Different forms of tinea pedis and their etiologic agents are shown in table 3. Tinea pedis involving the dorsal surface of the foot is shown in figure 1. For uncomplicated tinea pedis, treatment with topical broadspectrum imidazole, allylamine cream, or ciclopirox olamine will help control the fungal infection and may prevent secondary bacterial infections. Oral therapy is required for severe disease and chronic types of involvement. Tinea cruris (often with truncal involvement) follows tinea pedis and onychomycosis in frequency; it presents as an expanding scaling plaque of the upper thighs and groin, with central clearing and a red elevated border (figure 2). Scrapings are mandatory in analysis of groin rashes since SD of the groin is common and may mimic tinea. Tinea corporis in the setting of HIV disease virtually always is tinea curis that has extended beyond the groin into the trunk. This extensive form of tinea occurs in hot, humid climates and may be seen at all levels of

immunosuppression. In severely immunosuppressed patients with AIDS, lesions may have little inflammation and often lack the elevated border and central clearing typical of tinea (anergic tinea). They are recognized as sharply marginated areas of hyperkeratosis resembling dry skin. The penis and scrotum may also be involved; this is not noted in non-HIV-infected patients. Tinea capitis in the adult and tinea faciei are other, less common patterns of dermatophytosis associated with HIV infection. Although not common, Majocchi's granuloma (fungal folliculitis and perifolliculitis) is observed in HIV-infected patients. These conditions respond to systemic antifungal therapy with imidazoles or triazoles. Onychomycosis. Toenail infection in HIV-positive patients is common. In the HIV-uninfected population the distal subungual pattern is the most common and occurs when fungus invades the nail bed in the distal hyponychial area. As the disease progresses, the offending organism advances proxially, growing into the nail bed and eventually invading the undersurface ofthe nail plate. Proximal white subungual onychomycosis is the rarest form of onychomycosis in the general population. This form has been associated with AIDS [13] and is considered an early clinical marker of HIV infection. Here, the fungus spreads under the proximal nail fold, establishes itself in the epithelium of the nail fold and nail bed, ventrally invades the nail plate, and then grows distally [14]. The clinical picture is

Correlation between occurrence of dermatomycosis and level of immunity in patients infected with HIV.

Table 2.

Table 3.

Skin condition(s) Seborrheic dermatitis, onychomycosis Candidiasis, pruritus ani Eosinophilic folliculitis NOTE.

Table is modified from (12].

Level of immunosuppression: stage of HIV infection (CD4 cells/mm 3) Early stages (>400) Symptomatic stages (200-400) AIDS «200)

Tinea pedis: clinical forms and common etiologic agents.

Clinical form

Prevalence

Interdigital

Common

Vesicular Moccasin

Occasional Frequent

Common agents Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton jloccosum Trichophyton mentagrophytes Trichophyton rubrum

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Figure 1. A patient with tinea pedis. Spreading infection can be seen on the dorsal surface of the foot.

a white hue under the proximal nail plate in the region of the lunula (figure 3). The nail plate is either smooth and intact or very friable, with a consistency of plaster [15]. The mycologic findings of one study of HIV-positive patients are summarized in table 4. Trichophyton rubrum was the most common dermatophyte (58%). M. furfur was the only etiologic agent isolated from the infected nails of two patients. Because onychomycosis requires long-term therapy and not all patients with dystrophic nails have fungal infection, it is necessary to make a correct diagnosis. Direct microscopy of potassium hydroxide preparations and fungal cultures of the nail are sufficient to establish diagnosis [16]. Fluconazole and itraconazole have proven to be effective in the treatment of onychomycosis. Therapy with pulsed itraconazole (200 mg twice daily for the first 7 days of each month for 4 months) has been utilized by Conant [12] and by us with success. Cutaneous Candidiasis

Most HIV-infected persons have some form of candidal infection during their illness [17]. Candida albicans is the etiologic agent. The most common yeast infections in HIV-positive patients are oral candidiasis and esophageal candidiasis. There are three typical manifestations of oral candidiasis: pseudomembranous, erythematous, and angular cheilitis [18]. Intertriginous infections can involve the groin, axilla, or inframam-

mary areas. The hallmark of candidal intertrigo is the presence of satellite pustules. Recurrent episodes of oral candidiasis usually occur in patients whose CD4 cell counts are