Herpes Simplex Virus Infection

Herpes simplex virus (HSV) infection causes substantial morbidity in patients with HIV. HSV can serve as a cofactor in the progression of HIV. This is suggested by simultaneous isolation of HSV and HIV from the same lesion, reduction of HIV shedding in coinfected individuals undertaking antiherpetic treatment, and data suggesting that HSV infection may adversely affect the progression of immunodeficiency in HIV-infected persons. Herpes labialis caused by HSV type 1 (HSV-1) is common in HIV. In the setting of HIV, it tends to be more aggressive and lesions tend to last longer ( Fig. 1 ). Herpes genitalis caused by HSV type 2 (HSV-2) is the most frequent genital ulcer disease among HIV seropositive patients. Herpes genitalis presents as vesicles, erosions, and ulcers on the genitalia. In patients with AIDS, the severity and duration of recurrent genital herpes may be more severe than that seen in normal hosts.

Herpes labialis is an HIV-infected patient.

Molluscum Contagiosum

Molluscum contagiosum caused by a poxvirus is common in HIV. Lesions are skin-colored, dome-shaped papules or nodules with central umbilication.

In the setting of HIV, molluscum contagiosum tends to be atypical and extensive ( Fig. 2 ). Atypical lesions may resemble other conditions, such as basal cell carcinoma, keratoacanthomas, and cryptococcosis. Although it is a clinical diagnosis, biopsy may be necessary to confirm the diagnosis. Histopathology shows intracytoplasmic inclusion bodies, called molluscum bodies or Henderson-Paterson bodies.

Disseminated molluscum contagiosum.

Treatment of molluscum contagiosum in HIV patients includes restoration of immune competence by highly active antiretroviral therapy.

In some patients, lesions may respond to immunomodulators, such as imiquimod 5% cream. Resistant lesions may be treated with cryotherapy, which involves application of liquid nitrogen onto the lesions for cold-induced cell destruction; however, this may not be possible in patients with extensive disease. Complications of cryotherapy are hypopigmentation, hyperpigmentation, and scarring.

Herpes Zoster

Herpes zoster is also common in HIV setting and tends to be multidermatomal ( Fig. 3 ). HIV patients often get recurrent episodes. It presents as painful blisters after a dermatome. The pain may be severe in some patients and they are more likely to require medical attention.

Herpes zoster on maxillary and mandibular divisions of trigerminal nerve.

Treatment of herpes zoster is aimed at speedy healing of skin lesions, limiting disease progression, pain reduction, and prevention of complications, such as postherpetic neuralgia.

Systemic antivirals, such as oral acyclovir (800 mg 5 times a day for 7–10 days) or valacyclovir (1000 mg 3 times a day for 7 days), are helpful. A combination of analgesics and antiinflammatories should be given for pain.

A common complication of herpes zoster is postherpetic neuralgia, in which the pain of herpes zoster remains long after the skin disease has healed. Management of postherpetic neuralgia includes analgesics, antiinflammatories, and a tricyclic antidepressant, such as amitriptyline. Antiepileptics, such as carbamazepine, can also be used instead of amitriptyline.

Viral Warts

Human papillomavirus warts are also common in HIV patients. They tend to be multiple in these patients. They can present in the form of verruca vulgaris or verruca plana. HIV patients with viral warts must be on antiretroviral therapy to boost the immune system.

Topical therapies, such as trichloroacetic acid and podophyllin resin in a compound tincture of benzoin, applied on to the lesions may help. Podophyllin acts by way of antimitotic activity. Immunomodulators, such as imiquimod 5% cream, may also be helpful.

Ablative therapies, such as cryotherapy and curettage, can also help in patients with fewer lesions. Long-pulsed Nd:YAG laser has also been used successfully in some patients.

Staphylococcus aureus Infection

Staphylococcus aureus is the most common bacterial pathogen in HIV. It causes folliculitis, impetigo, ecthyma, and skin abscesses. Treatment of staphylococcal skin disease includes the use of systemic antibiotics, such as cloxacillin, and application of topical antibiotics, such as mupirocin or fucidin. The use of antiseptic solutions in bath water may prevent recurrent episodes.

Bacillary Angiomatosis

Bacillary angiomatosis is a vascular proliferative disease common in HIV. It is caused by Bartonella henselae and Bartonella quintana . The proliferative vascular lesions most commonly involve the skin but may be present in many other tissues, including lymph nodes, bone, brain, respiratory and gastrointestinal tracts, cardiac valves, and bone marrow.

It has been suggested that cutaneous lesions of bacillary angiomatosis may be a marker of systemic bacillary angiomatosis infection, especially in HIV-positive patients. Cutaneous lesions of bacillary angiomatosis are angiomatous papules and nodules, which bleed easily on contact ( Fig. 4 ). Treatment of choice is erythromycin (500 mg 4 times a day for 3 months). Doxycycline, ceftriaxone, and the fluoroquinolones can be useful.

Bacillary angiomatosis. These lesions bleed easily.

Syphilis

Syphilis is common in the setting of HIV, especially in HIV-positive men who have sex with men. Syphilis and HIV are particularly suited to being acquired together because both are sexually transmitted and the risk factors for acquisition are the same. Furthermore, ulcers of primary syphilis are known to facilitate the transmission of HIV.

In addition, syphilis has been reported to have immunologic effects on HIV infection, and HIV is known to modulate both the manifestations of syphilis and the serologic response to therapy.

It has been postulated that the presentation of syphilis differs between HIV-infected patients and patients without HIV infection.

First, HIV-infected patients with primary syphilis are more likely to have multiple chancres compared with non-HIV patients. In HIV patients, these ulcers tend to be larger and deeper.

Second, HIV-infected patients with secondary syphilis frequently have simultaneous genital ulcers, thus have overlap of primary and secondary syphilis ( Fig. 5 ). It is unclear whether the overlapping of stages of syphilis in HIV patients represents slower than normal healing of primary syphilis or an accelerated progression to secondary syphilis.

Overlap of primary and secondary syphilis in an HIV patient.

Third, HIV patients with syphilis have a higher likelihood of developing neurosyphilis. In HIV patients with syphilis, atypical serologic tests and even serologically defined treatment failures have been reported.

Cutaneous Tuberculosis

Cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multidrug-resistant pulmonary tuberculosis. Skin involvement with Mycobacterium tuberculosis is divided into 3 categories: inoculation tuberculosis, a primary infection of the skin that is introduced by an exogenous source; secondary tuberculosis, either contiguous or hematogenous spread from a primary focus that leads to skin involvement; and, lastly, tuberculids, which are hypersensitivity reactions to M tuberculosis components.

Lupus vulgaris remains the most common form of cutaneous tuberculosis, and it can be due to primary infection of the skin or due to hematogenous spread. Lupus vulgaris presents as an asymptomatic enlarging plaque that later ulcerates and become verrucous, fungating, and destructive ( Fig. 6 ). The nose and center of the face is a common area but any part of the body can be affected.

Verrucous, fungating lupus vulgaris on the face.

Scrofuloderma is another common form of cutaneous tuberculosis. It represents direct extension into the skin from an underlying tuberculosis focus, most commonly a lymph node or bone.

In HIV, dissemination of M tuberculosis to extrapulmonary sites, such as the skin, is more common, resulting in disseminated miliary tuberculosis of the skin, also known as tuberculosis cutis miliaris disseminata. It is an uncommon form of tuberculosis characterized by a papulopustular eruption and hematogenous dissemination of tubercle bacilli to multiple organs, including the skin, and often has a poor prognosis.

Papulonecrotic tuberculid occurs frequently in HIV patients. It is a symmetric eruption of necrotizing papules, appearing in crops and healing with scar formation ( Fig. 7 ). It is thought to be an immunologic response to M tuberculosis components in a previously sensitized patient after hematogenous spread from a focus of infection elsewhere.

Papulonecrotic tuberculid with atrophic scars.

Dermatophytes

Both dermatophytes and deep fungal infections are common in HIV. They are a major source of morbidity and mortality. Dermatophytes infections are caused by fungi that invade the superficial dead layer of the skin as well as keratinized tissues, such as hair and nails. They occur commonly in temperate and tropical climates of Africa, and HIV-positive patients are particularly susceptible. In a study by Petmy and colleagues in Yaounde, Cameroon, 53% of HIV-positive patients were found to have at least 1 superficial fungal infection. The causative fungi are either geophilic, zoophilic, or anthropophilic, and they include Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes , Trichophyton rubrum, Trichophyton tonsurans , and Trichophyton violaceum.

Tinea corporis, tinea cruris, tinea pedis, and onychomycosis all occur commonly in patients with HIV infection. Tinea cruris presents as an expanding scaling plaque of the upper thighs and groin with central clearing and an active border ( Fig. 8 ). Tinea corporis in the setting of HIV disease virtually always is tinea cruris that has extended beyond the groin into the trunk. In severely immunosuppressed patients with AIDS, lesions may have little inflammation and often lack the elevated border and central clearing typical of tinea.

Tinea cruris. Note the active border and central clearing.

Onychomycosis is also common in HIV-positive patients. In non-HIV patients, the distal subungual pattern is the most common and occurs when the fungus invades the nail bed in the distal hyponychial area.

In HIV/AIDS patients, the proximal white subungual onychomycosis is the common type and is considered an early clinical marker of HIV infection. In HIV patients, the clinical manifestations of dermatophyte infections may be atypical, making a diagnosis difficult. To ensure a correct diagnosis, skin scrapings should be collected for potassium hydroxide preparations and cultures.

Dermatophyte infections in HIV respond well to topical antifungal agents. Systemic antifungals are reserved for extensive, chronic diseases.

Deep Fungal Infections

Deep fungal infections, such as cryptococcosis and histoplasmosis, are also common in HIV patients. Cryptococcus neoformans is a yeast with a predilection to the skin and the central nervous system. Cryptococcosis associated with HIV is common in Africa and Southeast Asia and is a frequent cause of death in patients with AIDS in these regions.

Skin lesions occur in up to 10% of all patients with disseminated cryptococcosis and include papules, ulcerated nodules, subcutaneous nodules, Kaposi sarcoma–like lesions, and molluscum contangiosum–like lesions ( Fig. 9 ). Central nervous system involvement is common and occurs in 75% of HIV-infected patients with cryptococcosis. Unfortunately, symptoms and signs may be subtle, making early diagnosis difficult. Ideally all patients with cutaneous cryptococcosis should have their cerebrospinal fluid examined because some patients may have cryptococcal meningitis with no symptoms and signs. Other areas that may be affected by cryptococcosis are the eyes, kidneys, prostate, adrenals, heart, liver, spleen, bone, muscles, and lymph nodes.

Cryptococcosis in an HIV patient with meningitis.

Histoplasma capsulatum is a dimorphic fungus that grows as an intracellular yeast in the host and as a mold in vitro. It is also a common deep fungal infection. The etiologic agent of histoplasmosis associated with AIDS is Histoplasma capsulatum var. capsulatum .

The clinical presentation includes fever, weight loss, hepatomegaly, splenomegaly, enteritis, chorioretinitis, endocarditis, meningitis, encephalitis, skin lesions, and pulmonary involvement. Cutaneous involvement occurs in 11% of patients owing to hematogenous dissemination from the pulmonary focus. Skin lesions are nonspecific and may be papules, patches, nodules, abscesses, plaques, pustules, and ulcers ( Fig. 10 ).

Ulcerative lesions of histoplasmosis in an HIV patient.

Histology of the skin lesions may be diagnostic but the small size of organisms may elude easy detection. In disseminated disease, blood cultures and bone marrow cultures have the highest yield of organisms.

In treatment of both cryptococcosis and histoplasmosis, amphotericin B is the drug of choice. The initial induction therapy is generally amphotericin B, 0.5 to 1 mg/kg/d, followed by maintenance therapy with fluconazole or intraconazole.

Treatment must be given for longer periods because recurrences are common in immunocompromised patients. Other deep fungal infections that can occur in HIV patients are coccidiomycosis, blastomycosis, paracoccidiomycosis, and sporotrichosis.