Cutaneous Manifestations of HIV Infection

Mary Ruth Buchness

Overview

The first organ that may be affected in human immunodeficiency virus (HIV) infection is the skin. Before the advent of highly active antiretroviral therapy (HAART), the inevitable decrease in CD4 cells with disease progression was accompanied by a variety of HIV-associated skin diseases. HIV infection was often suspected initially based on the occurrence of cutaneous diseases, such as Kaposi’s sarcoma (KS) or severe molluscum contagiosum, or in a patient with particularly severe or recalcitrant manifestations of a common skin disease, such as psoriasis.
With the use of HAART, the number and frequency of cutaneous manifestations have plummeted in the United States and other countries. Furthermore, in patients with advanced HIV infection, the cutaneous manifestations often remit spontaneously when HAART is started. Nonetheless, some patients have viral resistance to these drugs or personal or economic reasons for not taking HIV medications, and in this group, the severe cutaneous manifestations of advanced HIV infection may still be seen.
Acute HIV infection is characterized by a morbilliform rash resembling measles, and fever, lymphadenopathy, sore throat, and malaise may accompany the eruption.
As the number of CD4 cells decreases to fewer than 200/mm³ during the course of infection, signaling the onset of acquired immunodeficiency syndrome (AIDS), skin manifestations become more severe and increase in number.

Hiv-Associated Herpes Simplex
Hiv-Associated Herpes Zoster
Hiv-Associated Molluscum Contagiosum
Hiv-Associated Condyloma Acuminatum
Hiv-Associated (Epidemic) Kaposi’s Sarcoma
Hiv-Associated Bacillary Angiomatosis
Hiv-Associated Syphilis
Hiv-Associated Norwegian Scabies
Hiv-Associated Eosinophilic Folliculitis
Hiv-Associated Oral Hairy Leukoplakia
Hiv-Associated Oral Candidiasis
Hiv-Associated Aphthous Ulcers
Hiv-Associated Drug Eruptions
Hiv-Associated Pruritus
Hiv-Associated Seborrheic Dermatitis
Hiv-Associated Psoriasis
Hiv-Associated Lipoatrophy

HIV-Associated Herpes Simplex

24.1 Herpes simplex. Shown here is HIV-associated chronic ulcerated herpes simplex that is resistant to acyclovir. This patient is receiving intravenous foscarnet.

24.2 Herpes simplex. Mucosal papules are present in this patient with AIDS.

Basics

In the immunocompromised host, the clinical manifestations and course of herpes simplex virus (HSV) infection differ in patients with defective cell-mediated immunity, as seen in HIV infection. (See Chapter 6, “Superficial Viral Infections,” and Chapter 19, “Sexually Transmitted Diseases,” for a full discussion of HSV infections in immunocompetent hosts.)
Recurrent lesions may affect mucous membranes and possibly become chronic, centrifugally expanding ulcerations. These ulcerations last 1 month or more in an HIV-positive patient and are an AIDS-defining diagnosis.
Lesions may become resistant to acyclovir, or they may develop into chronic keratotic papules. Because acyclovir resistance is associated with prior treatment of suboptimal doses, it is important not to undertreat HIV-positive patients who also have HSV infections.

Description of Lesions

Initially, there are the typical grouped vesicles on an erythematous base, which evolve into pustules, erosions, and crusts.
Ultimately, the following lesions may occur:
- Chronic digital ulcerations (Fig. 24.1)
- Mucosal erosions or papules (Fig. 24.2)
- Centrifugally expanding ulcerations with scalloped borders
- Keratotic or wartlike papules or plaques (Fig. 24.3)

24.3 Herpes simplex. Crusted, wartlike papules are noted.

Distribution of Lesions

Intraoral areas, including the tongue, buccal mucosa, palate, and gingivae may be involved.
Chronic ulcerative lesions may appear in perianal areas. These lesions can extend into the intergluteal cleft (Fig. 24.4).
Keratotic lesions may occur in any location.

Clinical Manifestations

Lesions may be more severe and more extensive than in immunocompetent hosts.
Severe or chronic erosions, ulcerations, or keratotic lesions should alert the clinician to the presence of advanced immunosuppression.

Diagnosis

See Chapter 6, “Superficial Viral Infections,” and Chapter 19, “Sexually Transmitted Diseases,” for more detailed discussions.

24.4 Herpes simplex. Chronic ulcerated lesions and scattered intact vesicles are present in a patient with AIDS.

Differential Diagnosis

Herpes Zoster

Lesions of herpes zoster may involve only part of a dermatome and may be clinically indistinguishable from HSV lesions.
When in doubt, sufficient doses of antiviral medications are recommended for herpes zoster infection. Underdosing must be avoided.

Decubitus Ulcer

These lesions affect bony prominences in debilitated patients and do not extend to the intergluteal cleft.

Cutaneous Cytomegalovirus Infection

In cytomegalovirus infection, perianal ulcers develop as an extension of gastrointestinal involvement. Skin biopsy shows characteristic viral inclusion bodies.
In the keratotic type of cytomegalovirus infection, disseminated infection is associated with retinal findings, so an ophthalmologic examination is essential.

Disseminated Mycobacterium avium-intracellulare Complex

Patients may have oral ulcerations.
This infection is associated with severe systemic disease and fever in HIV-infected patients.

Disseminated Histoplasmosis

Patients may have oral and cutaneous ulcerations.
Disseminated histoplasmosis is associated with systemic disease.

Management

If the patient has malabsorption or if lesions do not respond to other treatment, acyclovir (5 to 10 mg/kg every 8 hours) is infused over 1 hour. The dosage interval should be increased in patients with renal failure.
Failure to respond to intravenous acyclovir indicates acyclovir resistance.
Acyclovir resistance can be prevented by avoiding undertreatment and intermittent treatment.
Foscarnet (40 mg/kg intravenously every 8 hours) is used in acyclovir-resistant patients.
Strains that recur after treatment with foscarnet are usually acyclovir sensitive.

HIV-Associated Herpes Zoster

Basics

Herpes zoster is most common in elderly patients and in immunocompromised persons, although it may occur in anyone who has a history of chickenpox.
See Chapter 6, “Superficial Viral Infections,” for a more detailed discussion.

Description of Lesions

Grouped vesicles or bullae on an erythematous base affect all or part of a dermatome.
Lesions evolve into pustules and crusts and may erode. Chronic ulcerations and crusted or verrucous lesions may occur.
Severe scarring may result (Fig. 24.5).

Distribution of Lesions

Any dermatome can be affected.
Disseminated herpes zoster virus may occur.
- Occasional dissemination may lead to 25 or more lesions outside of the primary and two contiguous dermatomes (Fig. 24.6).
- The disease usually begins with typical dermatomal herpes zoster virus that becomes widespread and chronic.
- The eruption may be indistinguishable from varicella.

Clinical Manifestations

Prodromal symptoms of pain and itching may be severe enough to lead to a suspicion of serious illness. For example, the prodromal pain of thoracic zoster has led to critical care unit admission to rule out myocardial infarction.
Regional adenopathy may occur.
Varicella pneumonia may develop.
Cutaneous lesions may become chronic in patients with AIDS.

24.5 Herpes zoster. This patient developed severe scarring from his infection.

24.6 Disseminated herpes zoster. Note the initial dermatomal involvement on the buttock. (Courtesy of Herbert A. Hochman, M.D.)

HIV-Associated Molluscum Contagiosum

24.7 Molluscum contagiosum. This patient has “giant” molluscum lesions on his arm.

24.8 Molluscum contagiosum. This HIV-positive patient has a large molluscum contagiosum lesion on the shaft of his penis as well as other scattered smaller lesions. Also note onychomycosis of his thumbnail, which is another sign of immunodeficiency.

Basics

Molluscum contagiosum is caused by a poxvirus; the condition is most commonly seen in immunocompetent children and less commonly in healthy adults.
Multiple and extensive facial lesions, as well as lesions with atypical morphology, should alert the practitioner to the possibility of HIV infection.
See Chapter 6, “Superficial Viral Infections,” for further discussion.

Description of Lesions

Papules may be dome-shaped or, more commonly, are atypical in appearance.
Size may be up to, or greater than, 1 cm (giant molluscum contagiosum).
Lesions may lack central umbilication or may have several umbilications.
Lesions on hairy areas tend to penetrate hair follicles.
Lesions may be extensive (hundreds to thousands in number) in patients with advanced AIDS.
Patients receiving HAART tend to have rare molluscum, with the more typical morphology seen in immunocompetent hosts.
The appearance of new lesions may follow a downward fluctuation in immunity caused by a concurrent infection, such as influenza.

Distribution of Lesions

All areas of the body may be affected (Fig. 24.7), but lesions are most common on the face and genitals (Fig. 24.8).
In men, possible extensive involvement of the beard area may result from shaving (see Fig. 6.18).

Clinical Manifestations

There is occasional tenderness or inflammation.
Lesions are often a great cosmetic concern to patients.

Differential Diagnosis

Disseminated Cryptococcosis

Cutaneous lesions may be clinically identical to those of molluscum contagiosum (Fig. 24.9).
Affected patients are usually systemically ill, although cutaneous involvement may be the first sign of illness.
Crush preparation with India ink shows encapsulated yeast.
When in doubt, biopsy can be used to identify the lesions.
Patients with cutaneous dissemination have neurologic involvement, and a faster diagnosis can be made by cerebrospinal fluid examination.

Disseminated Histoplasmosis

This is a less common cause of molluscum contagiosum–like lesions than cryptococcosis.
Cutaneous histoplasmosis is always indicative of systemic infection.

24.9 Disseminated cryptococcosis. Note the resemblance of these papules to those of molluscum contagiosum.

Management

Treatment is individualized for each patient. No specific treatment is universally more effective than any other.
Topical tretinoin is a useful adjunctive treatment in cases of molluscum contagiosum of the beard.
Surgical treatment is with curettage or liquid nitrogen cryosurgery.
Trichloroacetic acid 25% to 75% may be applied to individual lesions.
Podofilox (Condylox) 5% may be applied to lesions twice per day, 3 days per week.
Imiquimod 5% (Aldara) cream may be effective and should be used daily if possible.
Treatment is long term and is unlikely to eradicate all lesions unless the patient’s immunity improves. Lesions may remit spontaneously after the patient is started on HAART, and knowledge of this fact will sometimes persuade a reluctant patient to begin treatment for HIV infection.