HIV and Skin Disorders

HIV infection and its fulminant form AIDS are associated with immune deficiency, especially of the thymus dependent system. This can lead to opportunistic infections or infections that are more rampant that normal and these infections may involve the skin. In HIV positive children, low CD counts have been associated with infectious skin eruptions, whereas high CD counts are associated with skin disease associated with hypersensitivity reactions. A knowledge of the cutaneous manifestations of HIV can thus help to indicate the patient's immune status.¹

Immune surveillance has long been postulated as a mechanism for the early detection and eradication of malignancy. There are some malignancies that are more common in this condition and some that are more aggressive.

Some cutaneous manifestations of HIV are so classical that they may lead to suspicion of the disease and early diagnosis with a greater chance of a successful outcome.² If a doctor has reason to suspect HIV and believes that a blood test is indicated, this must not be done surreptitiously but after the appropriate counselling for HIV testing.

According to the Health Protection Agency, in 2006 there were an estimated 73,000 persons of all ages living with HIV in the UK. Approximately 21,600 were unaware of their infection. The number of deaths among HIV-infected persons has fallen from 749 in 1997 to 497 in 2006. It should no longer be seen as a disease of homosexuals and drug abusers although they are at greatest risk. The fastest growing group are heterosexuals, male and female. Certain racial groups, especially West African, are at very high risk but no racial group is immune. As with alcoholism and other sexually transmitted diseases, no one should be regarded as too respectable and above suspicion.

• Acute primary HIV infection may lead to a transient, generalised, morbilliform eruption that is commonest on the upper thorax and collar area (100%), face (60%), arms (40%), scalp and thighs (20%). This appears as pink macules and papules of up to 1cm in size. Acute HIV syndrome occurs in 50 to 70% of recently infected patients and it occurs 3 to 6 weeks after exposure. There may be systemic symptoms and fever with the rash appearing 2 or 3 days later.
• 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.
• As immunosuppression occurs, nonspecific skin changes occur in which common disorders have atypical features . Recurrent shingles, numerous hyperkeratotic warts, treatment-resistant seborrhoic dermatitis and oral hairy leukoplakia are examples. The last is very highly suggestive of HIV infection and may be associated with Epstein-Barr virus.⁶
• In the later stages of HIV disease, chronic herpes simplex infection, molluscum contagiosum and cytomegalovirus appear.
• Mycobacterial infections and mucocutaneous candidiasis occur.
• Kaposi's sarcoma can occur before the onset of immunosuppression.
• Condylomata acuminata and verrucae appear early, without an increase in occurrence after the disease progresses, whereas HSV infections, molluscum contagiosum and oral hairy leukoplakia increase as the disease advances.
• Verrucous herpes infection, condyloma-like molluscum contagiosum and AIDS-associated pigmented or nonpigmented erythroderma may be seen.
• Leishmaniasis and miliary tuberculosis are also reported.

This was the first reported malignancy associated with HIV infection. Worldwide the prevalence with AIDS may approach a third but in western societies the figure is less than 5%. Most are homosexual men, with some increase in patients who acquire infection through heterosexual contact.

Kaposi's sarcoma is believed to be a proliferation of endothelial cells induced by human herpesvirus type 8.

It begins as pink macules that disseminate and become palpable. Three types have been identified - patch, plaque or nodular grade. Mucosal involvement is common.

Visceral disease is uncommon, affecting about 10% at diagnosis and investigation for such involvement is not necessary in the absence of symptoms.

The clinical progression in patients infected with HIV is more aggressive than in those who have the sarcoma without immune suppression. The advent of highly active anti-retroviral therapy (HAART) has complicated the prognostic relevance of Kaposi's sarcoma but it is considered that having KS as the first AIDS-defining illness combined with an increasing CD4 cell count improves prognosis, whereas having Kaposi's sarcoma at >50 years conveyed a poorer prognosis.

HIV increases the risk of various malignancies including primary lymphoma of the central nervous system, undifferentiated non-Hodgkin's lymphoma, squamous cell carcinoma, anorectal carcinoma and cutaneous malignancies. These malignancies are similar in incidence to those seen in other immunodeficient patients. Lymphoma, in particular, is associated with a more aggressive disease state.⁸ Some of these are associated with viruses such as Epstein-Barr virus and papillomavirus.

• B-cell non-Hodgkin lymphomas may cause skin nodules.
• Anal carcinoma and cervical intraepithelial neoplasia are associated with papillomavirus. They 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 carcinomas, Bowen's disease and metastatic basal cell carcinoma have occasionally been reported in patients with HIV. The usual dictum about BCC is that it does not metastasise.
• Malignant melanoma in patients with HIV appears to be more aggressive.
• Children with AIDS have a higher risk of developing leiomyosarcoma, but the incidence is still low.

Various herpes viruses can be a problem. There may be chronic perianal and perioral herpetic ulcers caused by HSV, recurrent typical dermatomal zoster caused by herpes zoster virus (HZV) and disseminated cytomegalovirus infection.

• Recurrent oral and anogenital HSV is common in patients with HIV and it may lead to chronic ulcerations. In children, herpes simplex stomatitis is more common than varicella zoster virus (VZV) and may become chronic and ulcerative.
• Acute disseminated varicella-zoster infection with atypical manifestations may occur. They include hyperkeratotic papules, folliculitis, verrucous lesions, chronic ulcerations, disseminated ecthymatous lesions and chronic varicella-zoster infection mimicking basal cell carcinoma. In children with HIV, the virus causes not just a more fulminant chickenpox but is more likely to produce shingles and encephalitis.⁹
• Epstein-Barr virus (EBV) has been implicated in the pathogenesis of oral hairy leukoplakia. It produces filiform white papules on the sides of the tongue. It is not pre-malignant, but it may be the initial sign of progressive immunosuppression. White plaques may be confused with oral candidiasis, lichen planus and geographic tongue.
• Cytomegalovirus produces ulcers in the perineal region. CMV infection has a poor prognosis with HIV.
• Widespread or recalcitrant warts may occur on the oral mucosa, the face, the perianal region and the female genital tract. The perianal and cervical lesions may be difficult to treat. Large plantar warts are caused by HPV-66 .
• The molluscum contagiosum virus produces small papules with central umbilication. In HIV infection, lesions may be widespread and atypical. The lesions may present 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 molluscum.

They may be superficial or deep.

• Recurrent and persistent mucocutaneous candidiasis is common with HIV infection. In the United States, recurrent vaginal candidiasis is the commonest presentation of HIV infection in women. Perhaps after excluding diabetes, HIV should be considered.
• In adults, generalised dermatophytosis, or tinea capitis, which is typically caused by Trichophyton rubrum, may suggest HIV infection.
• Pityriasis versicolor may be persistent and recurrent.
• Deep fungal infections such as coccidiomycosis, may also produce lesions on the skin.

• Impetigo and folliculitis may be recurrent and persistent , especially in children.
• Disseminated furunculosis, gingivitis, gangrenous stomatitis and abscess formation may occur.
• Tuberculosis is commoner in HIV infection. There may well be miliary tuberculosis and this can involve the skin. Mycobacterium infection is not just tuberculosis but in endemic areas leprosy may appear, probably in the lepromatous form as tuberculous leprosy infers an immunological response.
• Bacillary angiomatosis, which is caused by Bartonella henselae and rarely by B. quintana, usually produces red papules and nodules.
• Infection may occur with unusual species of mycobacterium such as Mycobacterium avium.
• Syphilis is not confined to history but occurs more frequently in patients who are either homosexual or bisexual or in those who use illicit drugs. Patients with syphilis have a high prevalence of HIV that may reflect promiscuity and life style. The ulcers of syphilis may facilitate the transmission of HIV. Patients with HIV infection with primary syphilis tend to have multiple ulcers compared with patients who are not infected with HIV.¹⁰ Rapid progression of secondary syphilis to tertiary syphilis occurs with HIV.¹¹ Seroconversion may be delayed and standard serologic tests for syphilis may be unreliable.

Atypical or Norwegian scabies is characterised by widespread hyperkeratotic, scaly maculopapular eruptions or crusted plaques. It tends to be associated with alcoholic tramps with very poor hygiene and possibly some immune inadequacy but it is also seen with HIV.

• Seborrhoeic dermatitis or eruptions like it are seen in many patients with AIDS. Seborrheic dermatitis may even be the presenting feature of HIV. The eruption has widespread inflammatory and hyperkeratotic lesions and may progress to erythroderma in some patients. The incidence may be higher in patients with AIDS related dementia or CNS disease.
• Psoriasis and Reiter's syndrome are more common. In some cases, existing psoriasis may become more severe with disseminated plaques and pustules.
• The typical skin lesions of pityriasis rosea may be seen.
• Acquired ichthyosis may begin on the lower extremities and spread in advanced disease.
• Pruritic papular eruption (PPE) is a common cutaneous manifestation with HIV. There are small, itchy, red or skin-coloured papules on the head, neck and upper part of the trunk. It is highly indicative of advanced immunosuppression.¹²
• Aphthous ulcers may be severe.
• Thrombocytopenia purpura, vitiligo, alopecia areata, sicca syndrome, pemphigoid and other autoimmune blistering diseases have been reported with HIV disease.
• Atopic disease may be reactivated. Atopic eczema can be severe in children.
• Urticaria may occur primarily or as a drug eruption . Cold urticaria has also been associated with HIV disease.
• Cutaneous vasculitis has been reported.
• Photosensitivity is more prominent. Photo-induced lichenoid drug reactions may be seen, especially on dark skin.

• Diffuse alopecia or alopecia areata may be inflammatory and permanent.
• Generalised alopecia can occur after treatment with indinavir, an anti-retroviral agent.
• Elongation of the eyelashes and softening and straightening of the scalp hair may be seen.
• Beau's lines, telogen effluvium and pallor of the nail beds may accompany any chronic illness.
• Zidovudine may produce longitudinal, transverse, or diffuse melanin pigmentation of the nails but nail pigmentation has also been observed in patients with HIV who have never received the drug.
• Proximal subungual onychomycosis is highly suggestive of HIV disease.

• Morbilliform drug eruptions occur in around two thirds of patients who are treated with co-trimoxazole. Nowadays this is rarely used in British general practice but it is the drug of choice for Pneumocystis jiroveci (carinii) pneumonia that is an opportunistic infection that is typical of AIDS. Reddish macules and papules can become permanent after the treatment is stopped.
• Toxic epidermal necrolysis has been reported with antibiotics, fluconazole, clindamycin and phenobarbitone in patients with HIV.
• Drug eruptions are the most common cause of erythroderma in patients with HIV.

Management is as for the particular skin condition plus specific treatment for the HIV. Treatment may have to be more prolonged and aggressive than normal. Immunomodulatory therapy may be very useful in the treatment of viral infections associated with HIV.¹³ Imiquod is useful for treating anogenital warts in HIV-positive patients and may help to prevent progression to anal cancer.¹⁴ In Kaposi's sarcoma, the use of antiretroviral agents is certainly beneficial but there is also a place for specific therapy against the tumour.¹⁵ Other options include local radiotherapy and chemotherapy.⁷