Bullous impetigo is most common in hot, humid weather, presenting as very superficial blisters or erosions, most commonly seen in the groin or axilla. Because the blisters are flaccid, they are short-lived; often only erosions or yellow crusts are present. These lesions closely mimic cutaneous candidiasis.(7)

Ecthyma is an eroded or superficially ulcerated lesion with an adherent crust. Under this crust is often a plane of purulent material teeming with staphylococci. Removal of this crust is necessary to treat the lesion topically.

Folliculitis due to S. aureus occurs most commonly in the hairy areas of the trunk, groin, axilla, or face, especially in men who shave. Follicular pustules are the primary lesion. Gram's stain and culture confirm the diagnosis and allow selection of appropriate antibiotic therapy, such as dicloxacillin (500 mg 4 times daily). Often the follicular lesions of the trunk are intensely pruritic and may be mistaken for other pruritic dermatoses, such as scabies.(7) About 50% of HIV-infected persons with scabies have coexistent S. aureus folliculitis. Occasionally, follicular lesions extend more deeply, forming abscesses. Rarely, all follicles across several square centimeters are infected, forming a large, violaceous, hidradenitis-like plaque. The plaque may be studded with pustules and have deep tracts connecting infected follicles. These plaques may mimic KS, but overlying pustules are quite unusual in KS (Figure 1). Rarely, abscess of the muscle (pyomyositis) may occur.(6-10)

The depth of the infection determines the treatment of cutaneous staphylococcal infections. Very superficial lesions, like bullous impetigo, often respond to a 7- to 10-day regimen of an appropriate antistaphylococcal antibiotic, such as dicloxacillin (500 mg given orally 4 times daily). Deeper lesions often require courses of treatment lasting for months. In addition, combinations of antibiotics, especially a penicillinase-resistant penicillin or first-generation cephalosporin plus rifampin (600 mg once daily), are often necessary to clear the infection.

Adjunctive topical therapy is helpful in beginning treatment and reducing recurrences. Washing the infected area once daily or every other day with an antibacterial agent (Hibiclens, Betadine, or benzoyl peroxide wash) helps remove crusts, dries lesions, and decreases surface bacterial concentration. Topical antibiotics (clindamycin 1% or erythromycin 2% solutions) applied twice daily may be used in chronically infected areas.(11)

Loculated abscesses must be incised and drained when fluctuant if antibiotics are to be effective. When cellulitis of any significance or symptoms of bacteremia are present, hospital admission for treatment with intravenous antibiotics is appropriate. Intranasal mupirocin may reduce carriage rate and prevent relapses. Chronic oral antibiotics may be required in some patients.(5)

Bacillary angiomatosis, a treatable opportunistic infection, was initially reported as atypical subcutaneous infection in patients with advanced HIV disease(12) and as epithelioid angiomatosis.(13) The agents causing this infection, initially designated as Rochalimaea, have been reclassified as Bartonella. The term bacillary angiomatosis is being replaced by Bartonella infection because the infectious agents causing this condition have been identified as two species of Bartonella - B. henselae and B. quintana.(1,2,14) These bacteria, closely related to rickettsiae, are extremely difficult to culture. As proposed initially by Le Boit, Koehler, and others at the University of California, San Francisco, one of the agents causing bacillary angiomatosis, B. henselae, is associated with most cases of cat scratch disease. One epidemiologic study has demonstrated cat exposure and cat scratches as risk factors for acquiring bacillary angiomatosis.(15)

Bacillary angiomatosis initially was considered primarily a disorder of the skin, but systemic involvement is common. Visceral disease may include osseous lesions,(16) hepatic and splenic involvement,(17) lymph node disease, pulmonary lesions,(3) brain lesions,(18) and widespread fatal systemic involvement.

The most characteristic cutaneous lesions of bacillary angiomatosis resemble pyogenic granulomas -- fleshy, friable, protuberant papules-to-nodules that tend to bleed very easily (Figure 2). In addition, deep cellulitic plaques and subcutaneous nodules may occur. Lesions number from a few to hundreds. Clinically, the skin lesions are frequently misdiagnosed as vascular tumors, especially KS. A prominent vascular proliferation that forms an elevated papule histologically characterizes the lesions (Figure 3). Neutrophilic leukocytes are prominent in the interstitium. Basophilic aggregates are found adjacent to the vascular lumina, representing collections of the bacterium. Diagnosis is confirmed by identifying the causative organism in affected tissue using silver stains or electron microscopy.

Systemic findings such as fever, night sweats, weight loss, and anemia are common in patients with bacillary angiomatosis. Reports describe mucosal lesions of the conjunctiva and upper respiratory tract.(3) Visceral lesions may be as or more common than cutaneous lesions. Involvement of the liver and spleen with or without skin lesions is the most commonly diagnosed form of visceral disease.(17) These patients present with abdominal pain, fevers, elevated levels on liver function tests, and hepatosplenomegaly. Liver and spleen biopsies may show large ectatic vascular spaces, a pattern called peliosis. Abundant bacilli are adjacent to these vascular spaces. Osseous lesions manifest as bone pain and may precede the appearance of skin lesions.(16) Routine radiographs reveal a lytic lesion at the site of pain. Bone scans rarely reveal additional asymptomatic lesions. Isolated lymph node enlargement is another presentation. The diagnosis of visceral disease is made on the basis of biopsy of the affected organ and examination with silver stains or electron microscopy. In the untreated patient, fatal widespread visceral disease may occur.(17)

Treating affected patients with erythromycin in full doses (500 mg orally 4 times daily) resolves the lesions, as does treatment with doxycycline (100 mg orally twice daily). Cutaneous lesions usually resolve in 3 to 4 weeks, but therapy should continue for at least 8 weeks. Patients with documented visceral disease should receive at least 4 months of therapy. Relapses can occur if treatment is not continued appropriately.(18) In vitro sensitivities as currently performed do not correlate well with clinical response. Unlike KS, bacillary angiomatosis lesions do not respond to radiation therapy.(19)

Early in the HIV epidemic, chronic persistent infection with herpes simplex virus (HSV) was recognized in patients with advanced HIV disease.(23) Today, this syndrome is a Centers for Disease Control (CDC)-defined index infection in establishing an AIDS diagnosis.(24)

As long as the host immune system is still reasonably intact, the course of genital and orofacial HSV recurrences may be similar to the course in non-HIV-infected patients. Clinicians should consider HSV in evaluating all ulcerative lesions, particularly perirectal ulcers and nonhealing ulcers anywhere on the body.

Lesions may appear as grouped blisters that rupture, crust, and heal in 7 to 10 days. More commonly, ulceration is the finding with no prior history of blisters. Once severely immunosuppressed, HIV-infected persons often experience chronic lesions that continue to expand and form large, crusted erosions 2 to 10 cm or larger in diameter (Figure 4). Lesions may be quite painful, especially if located perianally or periorally. Periungual infection is another characteristic manifestation of HSV-2 infection in the HIV-infected patient; all paronychial lesions should be cultured for HSV.(25)

A Tzanck smear taken from the edge of the ulcer, stained with Giemsa or methylene blue, when positive for multinucleated epithelial giant cells gives rapid diagnosis. Alternatively, fluorescent antibody testing or viral culture are diagnostic. If these are negative and clinical suspicion of HSV is high, clinicians should perform a biopsy of skin from the edge of the ulcer. A portion of the tissue should be cultured for viruses, which may be positive even when swab cultures are negative. In addition to routine histologic examination, clinicians should perform special stains and cultures for other possible infecting organisms, including spirochetes.

Oral acyclovir is extremely useful in managing HSV infections in HIV-infected patients. In the immunocompetent HIV-infected patient, either intermittent or chronic suppressive therapy may be used. The immunosuppressed patient with chronic ulcerative lesions should receive acyclovir (200 to 400 mg orally 5 times daily) until the ulcers heal, which may take several weeks. Then, chronic suppressive therapy should be instituted with acyclovir (400 mg orally twice daily) to reduce recurrences. The newer acyclovir analog antiviral agents are available with better absorption and higher bioavailability. Famciclovir (250 mg 3 times daily) and valaciclovir (100 mg twice daily) are alternatives.

Untreated HSV lesions tend to enlarge slowly. New lesions at distant sites may appear, probably due to cross-contamination rather than to hematogenous spread. It is unusual for HSV infections to disseminate, even in severely immunosuppressed HIV-infected individuals.

HSV may rarely cause a necrotizing folliculitis that appears as 0.2- to 1.0-cm papules with firm central crusts. A biopsy is usually required to establish the diagnosis, because the site of infection is the epithelium along the hair shaft in the dermis.

Large chronic perianal, perioral, or periungual ulcers that fail to heal with acyclovir treatment are often due to thymidine-kinase-negative, acyclovir-resistant HSV-2.(26-32) Treatment with foscarnet(29-32) and continuous-infusion acyclovir(33) is beneficial. Unfortunately, recurrences may also be resistant to acyclovir and, rarely, foscarnet.(27) The correct management of acyclovir- and foscarnet-resistant HSV is difficult, but trifluridine ophthalmic solution may be tried.(34)

Varicella zoster virus (VZV) infection is commonly seen early in the course of HIV infection, particularly in healthy-appearing individuals, before the onset of other symptoms.(35-39)

Because most HIV-infected persons have had varicella previously, the initial manifestation of VZV infection is usually herpes zoster. During the course of HIV disease, herpes zoster often precedes thrush and oral hairy leukoplakia by about 1 year,(37) making it an important early finding and raising suspicion of HIV infection in persons at risk.

Unlike zoster in individuals without HIV infection, this dermatomal eruption may be particularly bullous, hemorrhagic, necrotic, and painful in HIV-infected persons. The duration of blisters and crusts is usually 2 or 3 weeks. The approximate duration of significant pain is also 2 or 3 weeks. Necrotic lesions may last for up to 6 weeks and heal with severe scarring. This dermatomal scarring is characteristic of HIV-infected patients and should be sought when evaluating at-risk individuals. In severe cases, and occasionally in severe cases in non-HIV-infected persons, excruciating and disabling pain may last for many months.

Recurrences have been reported in up to 25% of African HIV-infected persons with herpes zoster.(38) This number is about 5% higher than that seen in San Francisco.(40) As immune suppression advances, recurrent episodes may increase in severity.

Dissemination of VZV in HIV infection is fortunately uncommon.(41) VZV does disseminate more commonly in HIV-infected persons than does HSV, however, so all disseminated herpetiform eruptions should be considered VZV until proven otherwise, and high-dose acyclovir should be given. The clinical manifestations of disseminated VZV infection include typical widespread Tzanck-positive blisters with or without an associated dermatomal eruption. In addition, chronic disseminated VZV may present as widespread ecthymatous ulcers or hyperkeratotic verrucous lesions.(42-44) This verrucous pattern often appears with prolonged infection that has been treated with acyclovir.(45) VZV strains cultured from verrucous lesions in patients failing acyclovir therapy are often acyclovir-resistant, thymidine-kinase-negative mutants of VZV.(42-44)

A less common manifestation of VZV infection in HIV infection is persistent, chronic, localized herpes zoster. Patients may develop typical herpes zoster that either fails to clear with acyclovir therapy or immediately recurs after therapy. Although dissemination does not occur, lesions fail to resolve with increasing doses of acyclovir, and patients eventually develop chronic localized zosteriform thymidine-kinase-negative VZV infection. Children with HIV infection may frequently develop primary, recurrent and persistent VZV infection.(46)

The use of corticosteroids in therapy for VZV infection in HIV-infected patients is somewhat controversial. Elderly patients without HIV infection are often given relatively high doses of oral corticosteroids for several weeks to prevent post-zoster neuralgia, although the efficacy of this treatment is debated. Systemic steroid therapy for VZV infection usually is not recommended for HIV-infected patients because of a theoretic risk of additional immunosuppression.

Because acyclovir reduces the initial pain, speeds healing, and reduces the risk of VZV dissemination, all VZV-infected patients with HIV disease should receive acyclovir treatment and their therapy should be initiated as soon as possible. The patient's immune status and pattern of zoster determines the method of administration.

Oral Acyclovir

If the patient has a reasonably intact immune system and does not have clinical features of disseminated or visceral infection, and if lesions are not near the eye (trigeminal nerve), then oral acyclovir is probably adequate and beneficial. Recommended doses for treating VZV are much higher than those for HSV because of the relative insensitivity of VZV to this medication. A dosage of 800 mg orally 5 times daily for 5 days is recommended. Therapy should continue at least 5 days beyond the last day of blister formation. Some authors believe that intravenous administration is more effective than oral.(47) Fortunately, side effects from this drug are rare, even at these high doses. Famciclovir (500 mg) and valaciclovir (1000 mg) may be given only three times daily but must be dose adjusted in the setting of renal impairment.

Intravenous Acyclovir

Intravenous acyclovir (10 mg/kg 3 times daily) is indicated when the patient's immunosuppression is significant (CD4 < 200 plus additional immune repression, e.g., lymphoma), when disseminated or visceral lesions are present, and when VZV affects the ophthalmic branch of the trigeminal nerve (eyelid or tip of the nose especially). The possible increased risk for herpetic keratitis, retinal vasculitis, and uveitis supports intravenous treatment of persons with such VZV infections.(48) Only intravenous acyclovir is guaranteed to reach plasma levels adequate to inhibit all VZV strains. Treatment should continue until the lesions are well crusted (usually about 7 days), after which full doses of oral acyclovir may complete the therapy. Treatment should continue for 10 to 14 days. Early and vigorous treatment may prevent the severe necrotic forms of zoster and help relieve the terrible pain that can occur. Acyclovir treatment does not appear to reduce the risk of postherpetic neuralgia. Other treatments for VZV consist mostly of analgesics and topical care of skin lesions. In mild cases, soap and water are adequate for bathing skin lesions, but in severe cases, compresses (2 or 3 times daily) help remove necrotic debris. Use of an antibiotic ointment after such treatment, such as silver sulfadiazine (Silvadene; Marion Merrell Dow, Kansas City, MO) or bacitracin, keeps the scabs soft, helps prevent them from sticking to dressings, and may also prevent secondary infection. Capsaicin cream (Zostrix; Genderm, Lincolnshire, IL), a substance P depletor,(49) may reduce both acute and chronic zoster pain. It may be applied to the lesions 5 times daily until the pain is controlled; rebound pain may occur when Zostrix use is discontinued.

On initial exposure to VZV, a disseminated blistering eruption called varicella (chickenpox) usually occurs. This presentation is followed by lifelong immunity, but dormant virus can later reactivate dermatomally, causing herpes zoster. Not surprisingly, varicella occurs in HIV-infected persons. HIV-infected persons with no prior history of varicella may on exposure develop typical chickenpox. In HIV-infected children and adults, however, varicella may be severe, cause visceral disease, and be fatal.(50,51)The predisposition for visceral disease seems greater in children than in adults with HIV disease. Prior VZV infection and the presence of anti-VZV antibodies do not protect the HIV-infected person from developing clinical lesions of varicella. Recurrences or persistence of varicella can occur despite acyclovir therapy. One possible explanation is the difficulty in achieving adequate blood levels of acyclovir during oral therapy.(43)

The number of reported HIV-infected persons with varicella is small, so it is unclear which are the best treatment strategies. Clinicians should probably give acyclovir to all HIV-infected persons with varicella. Adults who are feeling well, have normal chest radiographic findings, and have no evidence of visceral disease may be treated with oral acyclovir (800 mg 5 times daily for 10 to 14 days). For pediatric use, oral doses from 1,000 to 3,000 mg/m² may be used in HIV-infected children with uncomplicated varicella. This therapeutic approach must be used with extreme caution, and intravenous acyclovir must be instituted if healing is not prompt. Oral therapy with acyclovir may predispose patients to subsequent chronic cutaneous VZV infection due to suboptimal blood levels of the drug.(43) HIV-infected persons with varicella who are not given oral acyclovir should receive intravenous acyclovir (10 mg/kg every 8 hours). The clinical status of the patient determines the length of therapy. Acyclovir therapy should continue at least until the lesions are completely healed.

Molluscum contagiosum is a superficial cutaneous viral infection manifested as 2- to 3-mm flesh-colored hemispheric papules. Characteristically, a faint whitish core is at the center of each papule, some of which may be slightly umbilicated. This eruption is seen commonly in immunocompetent young children (ages 3 to 8 years), whose lesions are scattered widely over the face, arms, and trunk. In adults, this mild infection is usually sexually transmitted and occurs in the pubic area. In the nonimmunosuppressed child, lesions tend to last 6 to 12 months and then spontaneously resolve when the host develops resistance to the virus. Genital molluscum in the non-HIV-infected adult may be chronic.

Molluscum contagiosum occurs in approximately 10 to 20% of HIV-infected persons.(35) Early in the infection, the lesions are usually mild and localized to the groin or face. Once CD4 counts fall below 200, however, lesions tend to proliferate. They often number greater than 100 and may involve the face, trunk, and groin; there is a predilection for the eyelids.(52) Extensive molluscum contagiosum is a cutaneous marker of advanced HIV disease (CD4 < 50). At this stage, molluscum may extend onto mucosal surfaces of the lips or conjunctiva. Patients with advanced HIV disease are rarely cured of their molluscum. The finding of subclinical, microscopic infection in apparently normal skin may explain failure to cure patients.(53)

There are no known medical complications of molluscum contagiosum. It does not affect internal organs or even cause significant symptoms on the skin. The objective of treatment is therefore primarily cosmetic and preventive. Rarely, lesions become inflamed by rupture (simulating a secondary infection) or by the development of an associated dermatitis.

Light cryotherapy using liquid nitrogen can treat individual lesions. If this is not available, pricking the lesion with a large-gauge needle and removing the white core (molluscum body) may also be effective. Topical application of a tiny drop of cantharidin to each lesion for 3 to 6 hours will often induce sufficient inflammation to eradicate the lesions. Complete cure is difficult to achieve, and treatment is usually restricted to bothersome or distressing lesions. For refractory lesions, removal by curettage without cautery is very effective. Lesions of the lid margins should be removed by an ophthalmologist.

In HIV-infected patients, warts usually look like those seen in nonimmunosuppressed patients. Reports describe the rare occurrence of very extensive infections mimicking epidermodysplasia verruciformis in HIV-infected individuals. The warts seldom cause symptoms, except when on the soles of the feet and around the fingernails.

Treatment is primarily cosmetic; the exact same methods are used as in immunocompetent patients. In patients with symptomatic HIV disease, the results may be disappointing. Even in persons with normal immunity, relapse of warts after treatment is common. In advanced HIV disease, relapse is almost to be expected. Discomfort may limit the use of standard treatment. Liquid nitrogen cryotherapy can be applied every 1 to 4 weeks. Topical "anti-wart" medications containing salicylic and lactic acids dissolve keratin and help primarily by debulking the callous-like cap over the wart. They are applied daily under occlusion and may lead to complete disappearance of the lesions. In general, the treatment outlook for warts is poor in immunosuppressed patients. Referral to a dermatologist may be appropriate to help with these annoying lesions.

Condyloma acuminata are of special significance in persons with HIV infection. Cervical dysplasia and carcinoma are clearly associated with HPV infection.(54) Like the cervix, the anorectal area has a "transformation zone." HPV infection is very common in the genital and perianal area of homosexual men, especially those practicing receptive anal intercourse. In these men, even when visible warts are not present, cytologic dysplasia can be seen on smears.(55-57) Cervical dysplasia is also extremely common in HIV-infected women.(58) In addition, bowenoid dysplasia is seen in biopsy material of wartlike lesions (bowenoid papulosis) from the genital area of homosexual men.(59) This pattern correlates closely with the presence of potentially carcinogenic HPV type 16. In the absence of visible warts, oncogenic HPV is detectable in swabs from the anal area of patients with HIV disease.(56) Reports also describe HPV in the anorectal carcinomas of homosexual men.(60) These data strongly support the concept that anorectal cancer, like cervical carcinoma, is a consequence of sexually transmitted disease. HPV may be the inducing agent and by itself may be sufficient to produce cancer. HIV infection may be a cofactor enhancing this effect.

Unfortunately, anorectal warts in HIV-infected men are difficult to eradicate.(61) Nonetheless, an attempt should be made to eliminate all warts, especially those that are potentially premalignant lesions. The degree of cytologic atypia seen on biopsied condylomata may identify at least a portion of those harboring HPV with malignant potential.(62) The future availability of HPV typing may guide therapy. Until that time, complete eradication of all anogenital warts in HIV-infected men and women should be the goal. If this is impossible, then careful evaluation and close follow-up are clearly necessary to identify any genital neoplasms at the earliest and most treatable stage. Female HIV-infected patients must have regular gynecologic examinations and Papanicolaou (Pap) smears.(63,64)

Genital warts in HIV-infected persons are treated exactly the same way as in uninfected persons. Topical treatment with podophyllin or trichloroacetic acid may be applied weekly. At least 6 to 10 weeks of treatment is a reasonable "trial" of efficacy. Liquid nitrogen freezing has a slightly greater response rate. Persistent lesions may be surgically debrided and the bases cauterized. (For other than the most routine warts, we recommend sending the removed tissue for pathologic evaluation to rule out dysplasia.) Recurrence is almost universal.

The presence of external genital warts in women and perirectal warts in homosexual or bisexual men is usually associated with internal warts. Pelvic examination, Pap smear, and colposcopy are recommended in women, and anoscopy in men.

Superficial yeast and fungal infections can be broken down into the following three groups: thrush; intertriginous infections; and nail, paronychial, and foot infections.

Thrush

The most common form of yeast infection in HIV-infected persons is thrush. Angular cheilitis -- fissuring, maceration, and erythema of the corners of the mouth -- may accompany thrush. Treatment includes clotrimazole troches for oral thrush and an anticandidal agent such as nystatin (e.g., Mycolog ointment) or an imidazole cream for the affected lateral lips.

Intertriginous Infections

Either Candida or Tinea may cause intertriginous infection and may involve the groin, axillary vault, or inframammary areas. In these areas, candidiasis presents as a vivid red, slightly eroded eruption in the depths of the folds. The surface is wrinkled and a white membrane may coat the eroded surface. A hallmark of this rash is satellite pustules extending out centrifugally from the eroded areas. In males, the scrotum is often involved. Patient complaints of a burning pain may be as numerous as those related to pruritus. Tinea in the groin is usually pruritic. The scrotum is spared. The depth of the folds may be clear, and a well-demarcated, annular patch expands down the upper thigh. In more extensive cases, the lesions may extend through the pubic hair onto the lower abdomen and buttocks. Rarely, Tinea of the groin may extend to cover large areas of the body.(86) Both Candida and Tinea are diagnosed by potassium hydroxide examination of scales taken from the active border or a satellite pustule. Topical treatment is usually adequate and involves the application twice daily of an imidazole cream (clotrimazole, miconazole, or ketoconazole). Candidal lesions may be moist, so drying soaks with Burow's solution 1:20 may be initially helpful. Eroded lesions in intertriginous areas are very tender, so topical solutions may burn. Treatment should be continued for 21 to 28 days. Because relapses are common, intermittent prophylactic treatment may be required. In our experience, most HIV-infected patients referred for a refractory intertriginous eruption have seborrheic dermatitis or psoriasis of the groin. This condition presents as variably pruritic erythematous patches with a fine scale. There are no satellite pustules and no central clearing. Scrotal involvement occurs, but it is not erosive or tender, unless infected with bacteria. Rarely, Tinea causes groin rashes that persist because of using the wrong medication (e.g., nystatin), using a strong steroid with the antifungal agent (e.g., Lotrisone; Schering, Kenilworth, NJ), or trying to treat with oral ketoconazole alone. Tissue levels of oral ketoconazole may be insufficient due to poor absorption, if gastric acid production is low.(87) Addition of a topical imidazole is dramatically beneficial.

Candida Infection of the Nails

Both Candida and Tinea may infect the nails. Candida almost always affects the tissue around the fingernails, frequently presenting as a paronychia (inflammation of the tissues surrounding the nail). Findings include tenderness, erythema, and bogginess of the proximal nail fold. Pressure on the inflamed nail fold may express purulent material. Infection tends to be chronic, in which case the cuticle is lost and the nail plate may become ridged or dystrophic. Onycholysis (separation of the nail plate from the nail bed) may also occur. The nail plate itself is usually not invaded, so nail thickening, opacity, and crumbling are unusual. Chronic frequent exposure to water is a significant predisposing factor in candidal nail infection. Dishwashers, bartenders, and homemakers are at increased risk. Topical imidazole in solution or 2 to 4% thymol in chloroform twice daily is the initial therapy. The onycholytic nail must also be trimmed away so that the medication can be applied at the most proximal area of onycholysis. In refractory cases, fluconazole (100 mg daily), itraconazole (200 to 400 mg daily), or ketoconazole in doses of 200 mg to 400 mg daily for 2 to 4 weeks is helpful.

Tinea Infection of the Nails, Feet, and Hands

Tinea infection of the nails, feet, and hands is common in HIV-infected persons, but because it is also common in the non-HIV-infected population, it is not a specific marker of HIV infection. Tinea of the nail, in contrast to Candida, involves primarily the nail plate, favors the toenails over the fingernails, and does not cause acute paronychia. Nails become opaque and thickened, and may split or crumble. An associated Tinea infection of the soles or toe webs is common, manifested by chronic maceration, scaling, blistering, and/or thickening of the skin. Occasionally, the palms are involved in a similar manner. Tinea is especially likely if two feet and one hand are affected. Occasionally, Tinea will spread to hairy areas, especially the face and lower legs, causing a chronic plaque-like folliculitis that is easily mistaken for a chronic bacterial infection. Previous use of topical steroids may induce this pattern and mask the correct diagnosis. Tinea of the palms and soles is improved with topical imidazole therapy twice daily. Fingernail infection can be treated with griseofulvin, fluconazole, or itraconazole. The exact dosing for the two imidazoles is unknown, but probably is 100 to 200 mg (fluconazole) and 200 to 400 mg (itraconazole) daily. Treatment may be restricted to 1 week per month to reduce cost. Once treated, fingernail infection has a long disease-free period. Toenail infection is common and chronic and does not require therapy unless it causes discomfort. Fluconazole and itraconazole will likely be effective, but at a high cost for this largely cosmetic condition. Toenail infection is probably more likely than fingernail infection to relapse. Because relapse is common, constant use of topical antifungals is often necessary.

Deep (Systemic) Fungal Infections

Systemic infections reported in patients with symptomatic HIV disease include: cryptococcosis, histoplasmosis, sporotrichosis, aspergillosis, candidiasis, coccidioidomycosis, actinomycosis, and phaeohyphomycosis.(87-99) Only the first four present significant dermatologic problems. Cryptococcosis Cryptococcosis is common in patients with advanced HIV disease and usually presents as meningitis. Cutaneous lesions may precede or occur simultaneously with central nervous system (CNS) disease. Approximately 6% of patients with HIV disease and cryptococcosis have skin lesions. Lesions appear anywhere on the body but are most common on the head and neck; they typically present as pearly 2- to 5-mm translucent papules that resemble molluscum contagiosum.(89,90,95,97) Diagnosis is established by skin biopsy and culture. Cryptococcosis in the skin is an indication of disseminated infection, so appropriate work-up, especially of the CNS, is mandatory. Histoplasmosis Disseminated histoplasmosis is becoming an increasingly common problem in HIV-infected patients living in histoplasma-endemic areas; it occurred in more than 5% of patients with advanced HIV disease in one series from Houston, Texas.(96) Most cases probably represent reactivation of previous histoplasmosis infection rather than dissemination of newly acquired infections. This fact explains cases seen in New York City, Los Angeles, and San Francisco -- nonendemic areas -- among individuals who previously lived in areas endemic for the disease. Skin involvement occurs in about 10% of patients with advanced HIV disease with disseminated histoplasmosis.(96,99) The cutaneous lesions are not specific and present as erythematous macules, papules, maculopapular dermatitic lesions, pustules, acneiform lesions, ulcerations, and plaques. Histologic analysis of the skin may demonstrate granulomas; organisms are easily seen with special stains (e.g., methenamine silver). Therefore, skin biopsy is a good way to establish the diagnosis of disseminated histoplasmosis. Bone marrow biopsy and culture are positive in 69% of cases, and blood culture is positive in 27% of cases.(96) About 10% of patients with disseminated histoplasmosis present with sepsis, disseminated intravascular coagulopathy, and pulmonary, CNS, and renal failure. This syndrome is usually fatal. Sporotrichosis In non-HIV-infected persons, sporotrichosis most commonly presents as a disease of the skin and draining lymphatics. Rarely, sporotrichosis may disseminate. Disseminated sporotrichosis associated with HIV infection apparently begins as an asymptomatic pulmonary infection that spreads hematogenously to the skin and joints. Skin biopsies and cultures establish the diagnosis. Multiple widespread cutaneous ulcers and subcutaneous nodules are present.(91,92) Localized or disseminated sporotrichosis may be treated with amphotericin B. To avoid the difficulties associated with amphotericin B use, itraconazole at a dose of 400 mg daily or higher may be attempted in a patient with localized or non-life-threatening disease. SSKI is not recommended for HIV-infected patients with disseminated sporotrichosis. Aspergillus Cutaneous Aspergillus can occur as primary or secondary infection. The latter is from hematogenous spread or from direct invasion of underlying structures. Primary cutaneous aspergillosis is associated with local skin injury (from tape, intravenous catheter sites) and neutropenia. Lesions can appear as erythematous indurations with overlying pustules, hemorrhagic ulcers, or molluscum contagiosum-like lesions. Treatment includes systemic antifungal therapy (amphotericin B and/or itraconazole) along with surgical debridement and removal of predisposing agents (tape and catheters).(98)

Cutaneous presentations of primary and secondary syphilis in HIV-infected persons are usually similar to those in non-HIV-infected persons. In two reported cases of patients with advanced HIV disease who had cutaneous lesions of secondary syphilis, one had a true negative treponemal (FTA-ABS) and both had negative nontreponemal (VDRL) serologies.(100,101) Skin biopsies of cutaneous lesions demonstrated spirochetes and established the diagnosis. The patients' HIV infection apparently delayed development of serologic evidence of Treponema pallidum, resulting in negative tests. Thus, in the HIV-infected person, a negative serologic test may not be adequate to rule out secondary syphilis. Another report documents palmoplantar keratoderma as a manifestation of secondary syphilis in an HIV-infected person.(102) His immune response to T. pallidum was atypical.

Syphilitic infection of the CNS may occur early, even in the primary or early secondary stage, among both non-HIV-infected and HIV-infected persons. Clinical CNS disease may be manifest as early as a few months after infection.(103) Recommended therapies may not be adequate to treat or prevent this complication in non-HIV-infected persons. Early CNS relapse (even after standard treatment regimens) may be more common in HIV-infected individuals,(103-107) possibly because of a combination of impaired cell-mediated immunity due to HIV and suboptimal CNS levels of medication. Clinicians should carefully follow HIV-infected patients who have been treated with standard therapies for early syphilis. If CNS signs or symptoms develop, clinicians should perform appropriate evaluation for early CNS relapse, including lumbar puncture and VDRL of the cerebrospinal fluid (CSF). The CDC recommends that a CSF examination precede and guide therapy in all HIV-infected patients with latent syphilis present for longer than 1 year or for unknown duration.(108)

Because of reports of early CNS relapse, the CDC has issued special guidelines for the treatment of syphilis in persons with HIV infection.(108) They recommend that patients with early syphilis be treated with 2.4 million units of benzathine penicillin given intramuscularly at a single session. We recommend weekly intramuscular injections of penicillin G benzathine (Bicillin; Wyeth-Ayerst, Philadelphia, PA) 2.4 million units for 2 or 3 weeks. Even patients with early syphilis, however, require CSF examination if there are any clinical findings suggesting CNS involvement. For penicillin-allergic patients, hospitalization, desensitization to penicillin, and treatment with penicillin are recommended. Erythromycin is not recommended.(109) Quantitative nontreponemal tests are repeated at 1, 2, and 3 months and thereafter at 3-month intervals until a satisfactory serologic response occurs. If an appropriate fall in titer does not occur (two dilutions by 3 months for primary or by 6 months in secondary), the clinician should reevaluate and perform CSF examination.

For latent syphilis of longer than 1 year or of unknown duration, CSF examination is recommended for all HIV-infected patients. Benzathine penicillin should not be used to treat asymptomatic or symptomatic neurosyphilis in HIV-infected individuals.

Patients with neurosyphilis should be treated for at least 10 days with either aqueous crystalline penicillin G (2 to 4 million units intravenously every 4 hours) or with procaine penicillin G (2.4 million units intramuscularly daily) plus probenecid (500 mg orally 4 times daily). The correct therapy for HIV-infected persons with late latent syphilis and a normal CSF examination is not known. Weekly injections of benzathine penicillin (2.4 million units for 3 consecutive weeks) is suggested. Frequent serologic reevaluation is recommended to document the adequacy of therapy. Serologic response may be slower than in patients with early syphilis.

Two reports have documented Pneumocystis carinii cutaneous infection of the external auditory canal.(110,111) In these cases, polypoid lesions obstructed and protruded from the ear canals. Histology showed a dermal nodule composed of angiocentric perivascular amphophilic foamy material identical to that seen in P. carinii lung infection. Silver stain identified organisms. Neither patient had clinical pneumonia at the time of presentation, but one later developed P. carinii pneumonia (PCP). Both patients received trimethoprim-sulfamethoxazole (TMP-SMZ) and their cutaneous lesions healed.