eMedicine Specialties > Dermatology > Viral Infections
Cutaneous Manifestations of HIV Disease
Updated: Aug 12, 2009
Introduction
Background
Human immunodeficiency virus (HIV) infection continues to represent a major challenge and health problem worldwide. Two types of HIV have been identified. HIV-1 is the main cause of HIV infection throughout the world. HIV-2 is a prevalent cause of HIV infection in West Africa and is increasingly being identified in other areas. HIV-2 is less virulent than HIV-1.
Cutaneous manifestations, which may be the initial signs of virus-related immunosuppression, frequently occur in patients who are infected with HIV. Recognizing HIV-related skin changes may lead to the diagnosis of HIV infection in the early stages, which allows initiation of appropriate antiretroviral therapy.
Pathophysiology
HIV produces cellular immune deficiency characterized by the depletion of helper T lymphocytes (CD4+ cells). Most infections and neoplastic processes in the skin of a patient who is infected with HIV are altered or facilitated by the loss of CD4+ cells of the immune system.
Animal models show that Langerhans cells are the first cellular targets of the virus, which fuse with CD4+ lymphocytes and spread into deeper tissues. In studies with human subjects, glycoprotein 120, the viral-envelope protein, binds to the CD4+ molecule; however, the entrance of glycoprotein 120 into the cell requires a coreceptor, CCR5, which is a surface chemokine receptor. A rapid occurrence of plasma viremia with widespread dissemination of the virus is observed after the virus inoculation.
In humans, this viremia appears 4-11 days after mucosal entrance of the virus. The replication rate of the virus decreases with the virus-specific immune response in the host mediated by the cytotoxic lymphocytes that are specially targeted against the virus. Some soluble factors secreted by CD8+ cells may contribute to the reduction of the viral load. After this event, a viral set point is developed.
Frequency
United States
In 2001, approximately 5 million new HIV infections were reported, and 3 million deaths occurred due to HIV/AIDS. The risk of HIV infection within 3 high-risk groups, including young men who have multiple male sexual partners, persons who use drugs via injection, and persons who use crack cocaine, has increased as much as 4-5% per year.
International
Worldwide, more than 30 million persons are estimated to be infected with HIV-1, with 16,000 new cases daily.
Mortality/Morbidity
Cutaneous manifestations are frequently observed in patients with HIV infection. An autopsy analysis of HIV-seropositive patients revealed that 72% had opportunistic viral infections. Most patients were infected with cytomegalovirus (CMV) and herpes simplex virus (HSV).
The prevalence of clinically apparent molluscum contagiosum (MC) infection varies from 5-18% in different study series.
Cutaneous manifestations of HIV disease may be less responsive to usual treatment modalities. Patients with HIV have been found to have increased rates of cutaneous colonization by Staphylococcus aureus, and, in patients with advanced disease, sepsis and deep tissue infection can be common. In patients with bacteremia, S aureus has been isolated as much as 25% of the time. In one series of 646 patients with HIV, S aureus sepsis developed in 14 patients, and 10 of them later died. Risk factors for sepsis include intravenous catheter use, intravenous drug use, and trauma. AIDS-related neoplastic diseases also contribute to morbidity and mortality.
Race
In the United States, persons of color, including African Americans and Hispanics, are disproportionately infected.
Sex
HIV-1 infection frequently occurs in homosexual men. However, the spectrum of prevalence of dermatologic disease in women who are infected with HIV versus men who are infected with HIV differs only in a higher frequency of Kaposi sarcoma (KS) and oral hairy leukoplakia in men; men possibly have a higher frequency of onychomycosis. Women are at an increased risk for gynecologic infections, including recurrent candidiasis and human papillomavirus (HPV). Women most commonly acquire HIV infection through sexual intercourse.
Age
HIV infection commonly occurs in young adults. The virus may infect children by transplacental transmission or by breastfeeding. Some rare cases of children infected after sexual abuse by adults with HIV-1 have also been reported.
Clinical
History
The cutaneous manifestations occurring in HIV infection are mostly due to the alterations in the immune system.
- Acute primary HIV infection may lead to a transient, generalized, morbilliform eruption on the trunk and the arms.
- In the early asymptomatic stage of HIV disease, no signs of infection other than lymphadenopathy are present. This stage may last for 10 years or longer.
- With the onset of immunosuppression, nonspecific skin changes occur such as common disorders with atypical clinical features, including recurrent varicella zoster, numerous hyperkeratotic warts, treatment-resistant seborrheic dermatitis, and oral hairy leukoplakia.
- In the later stages of HIV disease, chronic HSV, MC, and CMV appear.
- Mycobacterial infections and mucocutaneous candidiasis occur.
- KS can occur prior to the onset of immunosuppression.
- According to Smith et al1 (who examined 912 patients infected with HIV-1) condylomata acuminata and verrucae are observed early, without an increase in occurrence as the disease progresses; whereas the incidence of HSV infections, MC, and oral hairy leukoplakia increases as the disease advances.
- Verrucous herpes infection, leprosy, condylomalike molluscum contagiosum, and AIDS-associated pigmented or nonpigmented erythroderma may be seen.2,3,4,5 Leishmaniasis and miliary tuberculosis are also concerns.6,7
Physical
Cutaneous manifestations of HIV disease can present as neoplastic, infectious, and noninfectious diseases.
- Kaposi sarcoma
- KS was the first reported malignancy associated with HIV infection.
- The worldwide prevalence of KS in patients with AIDS may approach 34%. In the United States, the prevalence of KS is less than 5% in patients with HIV. Most of the patients are homosexual men, with some increase in patients who acquire HIV infection through sexual contact.
- KS is an abnormally vascularized tumorlike lesion affecting skin, lymph nodes, and viscera. It is believed to be a proliferation of endothelial cells induced by human herpesvirus type 8. KS is promoted by various angiogenic and proinflammatory factors including HIV-Tat. In addition, the latency-associated nuclear antigen type 1 (LANA-1) protein is highly expressed in spindle cells, which is considered important in the maintenance of human herpesvirus type 8–associated malignancies.
- KS begins as pink macules that become disseminated and palpable. Purplish or brown macules and plaques may become nodular. Mucosal involvement is common.
- The clinical progression of KS in patients infected with HIV is more aggressive than the other clinical types of KS.
Man who has HIV infection and Kaposi sarcoma.
Man who has HIV infection and Kaposi sarcoma (same patient as in Media File 2).
- Other HIV-associated malignancies
- AIDS-related B-cell non-Hodgkin lymphomas may lead to skin nodules.
- Anal carcinoma and cervical intraepithelial neoplasia are papillomavirus-associated tumors associated with HIV disease. These tumors tend to be more progressive and aggressive.
- An increase in squamous cell carcinoma of the anal mucosa has been reported, especially in young homosexual men with HIV infection.
- Intraoral or multiple squamous cell carcinoma, Bowen disease, and metastatic basal cell carcinoma have occasionally been reported in patients infected with HIV.
- Malignant melanoma in patients with HIV appears to be more aggressive than in individuals without HIV. One study reported shorter disease-free and overall survival rates in patients with melanoma and HIV compared with patients with melanoma who did not have HIV.
- Children with AIDS have a higher risk of developing leiomyosarcoma, although the incidence is still low in this population.
- Since the advent of highly active antiretroviral therapy (HAART), the incidence of non – AIDS-defining cutaneous cancers—in particular basal cell carcinoma—among HIV-infected persons has exceeded that of AIDS-defining cutaneous cancers such as KS. In a prospective study, Crum-Cianflone et al found that 6% of HIV-infected persons developed a cutaneous malignancy over a mean follow-up period of 7.5 years. The development of cutaneous non–AIDS-defining cancers in this cohort proved to be associated with the traditional risk factors of increasing age and lighter skin color, rather than with CD4 lymphocyte counts, HIV RNA levels, or receipt of HAART.8
- Viral infections
- In patients infected with HIV, several viruses of the Herpesviridae family may lead to cutaneous disease, including chronic perianal and perioral herpetic ulcers caused by HSV, recurrent typical dermatomal zoster caused by herpes zoster virus (HZV), and disseminated CMV infection. Recurrent oral and anogenital HSV is common in patients infected with HIV, and it may lead to chronic ulcerations. In pediatric patients, herpes simplex stomatitis is more common than varicella zoster virus (VZV) and may become chronic and ulcerative. Patients with VZV may develop chronic ecthymatous VZV.
Old herpes zoster and Kaposi sarcoma in a patient with HIV disease.
- Acute disseminated HZV infection and atypical manifestations, including hyperkeratotic papules, folliculitis, verrucous lesions, chronic ulcerations, disseminated ecthymatous lesions, and chronic VZV infection mimicking basal cell carcinoma, have also been described. According to Leibovitz et al,9,10 chronic VZV infections associated with HIV-1 infection begin as vesicles and progress into necrotic, nonhealing ulcers.
- Epstein-Barr virus (EBV) has been implicated in the pathogenesis of oral hairy leukoplakia. Oral hairy leukoplakia, which is characterized by filiform white papules localized on the sides of the tongue, may develop in patients infected with HIV. Oral hairy leukoplakia has no malignant potential, but it may be the initial sign of progressive immunosuppression. White plaques may be confused with oral candidiasis, lichen planus, and geographic tongue.
- CMV infection
- CMV is a DNA virus in the Herpesviridae family. Ulcers in the perineal region are the most common presentation for CMV infection in patients infected with HIV-1. The concurrent involvement of other infectious agents, such as HSV, in the same lesions confounds the role of CMV in cutaneous lesions. HSV is proposed to be the initiating infection leading to ulcer formation, with CMV secondarily localizing in the granulation tissue.
- Nonspecific maculopapular eruptions similar to those affecting patients with EBV or papulovesicular, nodular, purpuric, and ulcerative lesions of CMV infection are observed in patients who are immunocompromised. However, cutaneous lesions are rarely observed in patients infected with HIV.
- Bournerias et al11 reported epidermal involvement in 2 patients infected with HIV.
- CMV infection of the eccrine ducts resulting in squamous metaplasia has been described in a patient with HIV.
- Diagnosing skin CMV infection in individuals infected with HIV is important. The presence of CMV infection is considered a poor prognostic sign in HIV disease.
- Widespread or recalcitrant warts may be observed on the oral mucosa, the face, the perianal region, and the female genital tract in patients infected with HIV. The perianal and cervical lesions may be difficult to treat. Large plantar warts caused by HPV-66 and an epidermodysplasia verruciformislike eruption, which is believed to be associated with HPV infection, have also been reported in patients infected with HIV.
- The MC virus is a DNA virus in the Poxviridae family. It replicates in the cytoplasm of epidermal cells. MC lesions are small papules with central umbilication. In HIV infection, MC may be widespread and atypical. The lesions may be observed on unusual sites, such as the face, neck, and scalp, and the lesions may be of unusual morphology and size. Such unusual forms include solitary, endophytic, aggregated, inflamed, and giant MCs. MCs mimicking sebaceous nevus of Jadassohn, ecthyma, and giant condylomata acuminata have been reported.
Young man with HIV disease and molluscum contagiosum on the lateral part of the eyebrow.
Molluscum contagiosum on the penile shaft in a patient with HIV disease.
- Superficial fungal infections
- Recurrent and persistent mucocutaneous candidiasis is common in patients with HIV infection. In the United States, recurrent vaginal candidiasis is the most common presentation of HIV infection in women.
- In adults, generalized dermatophytosis, or tinea capitis, which is typically caused by Trichophyton rubrum, may suggest HIV infection.
- Pityriasis versicolor may be persistent and recurrent in patients with HIV infection.
- Deep fungal infections
- Rarely, cutaneous cryptococcosis may be observed in patients with HIV infection. Clinical manifestations include cellulitis; papules; plaques; ulcers; or translucent dome-shaped papules with central umbilication, resembling MC.
- Cutaneous histoplasmosis may lead to red papules, a cellulitislike eruption, ulcerations, acneiform papules, or molluscumlike lesions in patients infected with HIV.
- North American blastomycosis may present as a disseminated maculopapular eruption in HIV disease.
- Systemic coccidioidomycosis may disseminate to the skin, usually as hemorrhagic papules or nodules.
- Bacterial infections
- Impetigo and folliculitis may be recurrent and persistent in HIV disease, particularly in children.
- Disseminated furunculosis, gingivitis, gangrenous stomatitis, and abscess formation can occur in patients with HIV infection.
- Bacillary angiomatosis, which is caused by Bartonella henselae and rarely by Bartonella quintana, usually manifests as red papules and nodules.
- Mycobacterial infections
- Mycobacterium tuberculosis; Mycobacterium avium-intracellulare complex; and, rarely, Mycobacterium kansasii may present as acneiform papules and indurated crusted plaques.
- M avium complex, a common opportunistic pathogen among patients with AIDS, usually manifests as disseminated disease involving the lungs, lymph nodes, and gastrointestinal tract. Primary cutaneous infections with M avium complex are extremely rare, and most cutaneous lesions are caused by dissemination. Cutaneous manifestations thus far reported include scaling plaques, crusted ulcers, ecthymalike lesions, verrucous ulcers, inflammatory nodules, panniculitis, pustular lesions, and draining sinuses. Localized skin involvement resembling sporotrichosis is unusual. Primary cutaneous M avium complex infection manifesting as sporotrichosislike lesions was described in a patient with AIDS.
- In patients with HIV, Mycobacterium haemophilum can also present as violaceous draining nodules and superficial ulcers on the extremities, trunk, head, and genitalia.
- Rarely, B quintana coinfection with M avium complex and CMV has been reported in AIDS patients.
- Syphilis
- Syphilis presents more frequently in patients who are either homosexual or bisexual or in those who use illicit drugs.
- A high prevalence of HIV seropositivity, as well as other sexually transmitted diseases, exists in patients with syphilis.
- Syphilitic ulcers are believed to increase HIV transmission.
- Most cases of syphilis that occur in HIV disease are clinically and serologically typical.
- Patients with HIV infection with primary syphilis tend to present more frequently with multiple ulcers compared with patients who are not infected with HIV.
- Rapid progression of secondary syphilis to tertiary syphilis and syphilis maligna has been reported in patients infected with HIV.
- Syphilis seroconversion may be delayed, and standard serologic tests that aid in diagnosing syphilis may be unreliable.
- Appropriate serologic follow-up to ensure an adequate response to treatment is important in patients infected with HIV.
- Scabies: Atypical or Norwegian scabies, which is characterized by widespread hyperkeratotic, scaly maculopapular eruptions or crusted plaques, can occur in patients with HIV infection.
- Leishmaniasis: Atypical disseminated leishmaniasis has been reported in an HIV-infected patient.
- Demodicidosis: Demodex folliculorum folliculitis may lead to a pruritic papular eruption (PPE) on the face and the upper part of the trunk in patients with HIV disease.
- Papulosquamous dermatoses of AIDS
- Generalized dry skin syndrome is frequently observed in patients with HIV infection. Xerosis may be the initial clinical manifestation of AIDS and is often a cause of pruritus.
- In the United States, pruritus has been reported in 4.5% of patients with AIDS.
- Seborrheic dermatitis
- According to Mathes et al,12 seborrheic dermatitislike eruptions are observed in 83% of patients with AIDS. Seborrheic dermatitis may be the initial cutaneous manifestation of HIV disease. The eruption, which is characterized by widespread inflammatory and hyperkeratotic lesions, may progress to erythroderma in some patients.
- Seborrheic dermatitis may be increased in patients with AIDS-associated dementia or CNS disease.
- The immune alterations caused by HIV infection may lead to psoriasis and Reiter syndrome. In some instances, preexisting psoriasis may become more severe with disseminated plaques and pustules.
- The typical skin lesions of pityriasis rosea may accompany HIV disease.
- Acquired ichthyosis may begin on the lower extremities and disseminate in advanced HIV disease. Acquired ichthyosis may be a marker of concomitant infection with HIV-1 and human lymphotropic virus II in persons who use intravenous drugs and have profound helper T-cell depletion.
- Eosinophilic folliculitis manifests as an idiopathic, highly pruritic, papulopustular eruption of sterile pustules involving the face, neck, trunk, and extremities.
- The serum immunoglobulin E (IgE) level and blood eosinophil count may be increased.
- Pruritic papular eruption
- PPE is a common cutaneous manifestation in patients infected with HIV. It manifests as small, itchy, red or skin-colored papules on the head, neck, and upper part of the trunk.
- The cause is not known. According to Boonchai et al,13 81.25% of patients with PPE have advanced immunosuppression.
Dull red, violaceous, maculopapular lesions on the upper part of the trunk in a 49-year-old man with primary HIV-1 infection.
- Hair and nail disorders
- Diffuse alopecia or alopecia areata may be associated with HIV disease and may be inflammatory and permanent. The apoptotic follicular stem cell population in higher proportion may represent a hair cycle disturbance in patients with diffuse alopecia related to HIV-1 infection.
- Generalized alopecia can occur in patients with HIV who are treated with indinavir, an antiretroviral protease inhibitor.
- Elongation of the eyelashes and softening and straightening of the scalp hair may be observed in HIV disease.
- Beau lines, telogen effluvium, and pallor of the nail beds are the general effects of the chronic illness.
- Zidovudine is associated with longitudinal, transverse, or diffuse melanin pigmentation of the nails; however, nail pigmentation has also been observed in patients with HIV who have never received zidovudine.
- Proximal subungual onychomycosis is usually a sign of HIV disease.
- Drug eruptions
- Morbilliform drug eruptions can occur in as many as 65-70% of patients who are treated by trimethoprim-sulfamethoxazole (TMP-SMZ) for Pneumocystis carinii pneumonia within 7 days of starting the therapy. Reddish macules and papules may be generalized and can become permanent after the discontinuation of the therapy. Sulfonamides may cause urticaria; erythema multiforme; toxic epidermal necrolysis; and systemic reactions, including fever, leukopenia, thrombocytopenia, hepatitis, and nephritis. Toxic epidermal necrolysis has been reported with antibiotics, fluconazole, clindamycin, phenobarbital, and chlormezanone in patients with HIV.
- Fixed drug eruption has been reported in 2 patients receiving saquinavir, an HIV-1 protease inhibitor.
- Drug eruptions have been reported as the most common cause of erythroderma in patients infected with HIV.
- Aphthosis: Severe aphthous stomatitis may be associated with HIV disease.
- Autoimmunity, atopic disease, and urticaria
- Thrombocytopenic purpura, vitiligo, alopecia areata, sicca syndrome, pemphigoid, and other autoimmune blistering diseases have been reported in association with HIV disease.
- Atopic disease may be reactivated by HIV disease. Atopic eczema may be severe in children infected with HIV. Increased serum IgE levels have been found in these children; however, increased IgE levels were not correlated with atopic symptoms.
- Urticaria may occur primarily or as a drug eruption in HIV disease. Cold urticaria has also been associated with HIV disease.
- Cutaneous vasculitis
- Cutaneous vasculitis has been reported with HIV disease.
- CMV and parvovirus B19 have been discussed in the etiology of HIV-associated cutaneous vasculitis.
- Leukocytoclastic vasculitis has been reported with indinavir treatment.
- Photosensitivity has been reported in patients with advanced HIV disease. In a study by Vin-Christian et al,14 patients with HIV were sensitive to UV-B light. Vin-Christian et al14 also showed that the patients who were most severely affected were sensitive to both UV-B and UV-A light. Photo-induced lichenoid drug reactions may be seen, particularly in dark-skinned patients.
- In patients infected with HIV, drug-induced pigmentation can occur on skin exposed to light.
Causes
- HIV infection frequently occurs in men who have multiple male partners and in individuals who use illicit intravenous drugs.
- Children may be infected by transplacental transmission and rarely by sexual abuse from adults infected with HIV.
- Health care workers are another group at risk for HIV disease.
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 Overview: Cutaneous Manifestations of HIV Disease |
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Further Reading
Keywords
Kaposi sarcoma, Kaposi's sarcoma, KS, human immunodeficiency virus, HIV, HIV-associated malignancy, viral infection, herpes simplex virus, herpes zoster virus, HSV, HZV, Epstein-Barr virus, EBV, cytomegalovirus, CMV, warts, molluscum contagiosum, MC, fungal infections, candidiasis, dermatophytosis, cryptococcosis, histoplasmosis, North American blastomycosis, coccidioidomycosis, bacterial infections, impetigo, folliculitis, bacillary angiomatosis, mycobacterial infections, syphilis, scabies, papulosquamous dermatoses, seborrheic dermatitis, drug eruptions, hair and nail disorders, cutaneous vasculitis, autoimmunity, atopic disease, urticaria, aphthous stomatitis, pruritic papular eruption, PPE, eosinophilic folliculitis, EF
