|Skin disorders are common in patients with HIV and may be manifestations of the infection or related to treatment. It is important to be aware of the possible conditions to accurately diagnose and manage them.
Alopecia, granuloma annulare, HAART therapy, HIV, ichthyosis, photosensitivity, pruritus, vasculitis, xerosis
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Up to 90% of HIV patients may develop a skin disorder. Since the introduction of highly active antiretroviral therapy (HAART), infectious skin diseases are now outnumbered by inflammatory, autoimmune and malignant skin conditions. Some of these have a particular association with HIV in terms of being more frequent or more severe.
There is in general an inverse relationship between CD4 count and the development of skin disorders,1 but they may occur at higher CD4 counts.
A diffuse non-scarring alopecia can develop in HIV infection, with chronic telogen effluvium being the main pathogenic mechanism. This occurs mainly in the late stages of infection, with a lower CD4 count.
The protease inhibitor indinavir can also cause a telogen effluvium up to some months after initiating therapy, which is unrelated to drug dosage or CD4 count.2
Erythroderma is an exfoliative erythematous dermatitis involving at least 90% of the skin surface. It has been documented in the context of HIV infection and may be the initial presentation.3 Causes are numerous, including atopic dermatitis, seborrhoeic dermatitis, psoriasis, cutaneous lymphoma, pityriasis rubra pilaris and drug reactions.4
Granuloma annulare (GA) is a chronic granulomatous dermal eruption of unknown aetiology. It can be associated with diabetes mellitus, thyroid disease, hepatitis B or C, malignancies or HIV-1 infection.
GA may be a manifestation of immune dysregulation. In HIV infection, it may present with unusual clinical features, such as oral lesions or perforating variants, and the generalised form is more common than the localised form.
It can present with skin-coloured, erythematous or violaceous dermal papules, plaques or nodules, which are either asymptomatic or associated with mild pruritus.5 The localised form may resemble Kaposi’s sarcoma, while the generalised form may look similar to pruritic papular eruption (PPE), illustrating the importance of skin biopsy in diagnosis.6
Treatment may not be required for asymptomatic localised lesions, but if they are symptomatic or generalised, topical or oral steroids may be considered.
Acquired ichthyosis can occur in association with concomitant HIV-1 and HTLV-II retrovirus infections. It may occur after profound T cell depletion, in association with increasing age.
Ichthyosis may develop in patients infected only with HIV-1, but occurs more frequently in those infected with both HIV-1 and HTLV-II.7
Lupus and dermatomyositis
HIV infection can rarely cause or present with a variety of autoimmune conditions, including systemic lupus erythematosus (SLE), sicca or Sjögren’s syndrome, Reiter’s syndrome, polymyositis and dermatomyositis.8-10
ANA can be significantly raised and may cause a dilemma about treatment. Autoimmune disease may also appear or temporarily flare up after initiation of HAART.
In addition, however, a paradoxical effect exists whereby some patients with autoimmune disease may be able to produce HIV-1 neutralising antibodies more readily than those without autoimmune disease. Antibodies to retroviral proteins have been demonstrated in primary Sjögren’s syndrome,11 and one patient with SLE has been shown to be able to produce HIV-1 neutralising antibodies, which enabled her to control her viral load without HAART.12
Cutaneous non-AIDS defining cancers, particularly basal cell carcinoma (BCC), are now much more frequent than AIDS-defining cancers, such as Kaposi’s sarcoma.
BCC: incidence higher in HIV patients despite HAART (Image: Dr Sara Ritchie)
A number of studies have shown that patients with HIV have an increased risk of developing non-melanoma skin cancers, and may develop these at a younger age than the general population, despite HAART.13
Incidence rates are not as high as in solid-organ transplant recipients, who disproportionately develop squamous cell carcinoma (SCC).
In HIV infection, BCCs outnumber SCCs, which parallels the general population, but incidence rates in HIV infection are higher, at up to 6%.14
Recurrence rates are also higher than the general population, despite HAART.15 Melanoma incidence may also be increased, despite the rising background incidence, again possibly despite HAART.16
HIV infection is known to be strongly associated with a higher prevalence and persistence of HPV infection, which can cause genital intraepithelial neoplasia. HAART was not found to decrease anal cancer risk,17 and data on incidence of anal cancer shows a higher incidence in the HAART era than the pre-HAART era.
Bowen's disease: early form of skin cancer (Image: Dr Sara Ritchie)
Photosensitivity in HIV infection can have increased prevalence and severity. Although it is usually a manifestation of advanced disease, it may also be an initial presentation.18
It may have a heterogeneous clinical presentation, with lichenoid, hyperpigmented or eczematous forms, including chronic actinic dermatitis, which may present at a younger age than normal.19,20
It occurs in sun-exposed areas, but may spread to sites not exposed to the sun and is more common in patients with black skin. Although photosensitivity can be due to HIV infection itself, using HAART can further increase its prevalence.21
Pityriasis rubra pilaris
Pityriasis rubra pilaris may be associated with HIV infection, and can occasionally be the first manifestation. It can present with unusual clinical features, such as lichen spinulosus lesions. The condition can improve with HAART, although typically has a poorer prognosis.22
PPE and eosinophilic folliculitis
PPE is characterised by multiple, discrete, intensely itchy skin-coloured papules, which are typically symmetrical and often excoriated. The face, trunk and arms are common sites.
PPE: biopsy is important in diagnosis (Image: Dr Gabriela Jimenez Diaz)
This is the most common non-infective skin disorder in HIV infection.23 Histologically in PPE, the hair follicles are normal, with a perivascular infiltrate of lymphocytes and eosinophils in the dermis.
This is histologically distinct from HIV-associated eosinophilic folliculitis, which shows a perifollicular infiltrate of eosinophils.
The differential diagnosis of itchy papules in HIV infection is wide, also including bacterial or fungal folliculitis, scabies and drug rashes, and these may be impossible to distinguish clinically. Skin biopsy from a fresh, unexcoriated lesion is important to establish the diagnosis and guide therapy.24
Both PPE and HIV-associated eosinophilic folliculitis may respond to HAART. Isotretinoin has also been demonstrated to be effective in HIV-associated eosinophilic folliculitis, at lower doses than normal of 20mg per day for six to eight weeks.25 Topical tacrolimus may also be effective and narrow-band UVB phototherapy can be helpful.26
Severe intractable idiopathic pruritus is common in some non-atopic HIV-infected patients, although this must always be a diagnosis of exclusion, and other causes, such as seborrhoeic dermatitis, eczema, psoriasis, PPE, scabies, lymphoproliferative disorders, systemic disease and medications, must be ruled out in these patients.
Idiopathic pruritus is associated with lower CD4 counts, which cause increased levels of IgE and hypereosinophilia. HAART reduces the prevalence,27 although the condition may often still be difficult to treat. One study showed that all patients taking oral therapies had more relief than those using topical steroids.28
Pruritus may be resistant to oral antihistamines. Doxepin, pentoxifylline and oral indometacin have also been tried.29 Phototherapy can be effective, although care must be taken when selecting patients in view of risks of photosensitivity and skin malignancies.
HIV infection can trigger new-onset psoriasis or exacerbate existing psoriasis.30 Human leukocyte antigen alleles in psoriasis and HIV-1 infection have structural similarity, and it appears that patients with psoriasis may be enriched for genetic variants that may help to protect against progression of HIV and contribute to antiviral immunity, which also predisposes to the development of clinical psoriasis.31
Psoriasis in HIV may become unstable, with a risk of progression to erythrodermic psoriasis. Psoriatic arthritis may also be more severe in HIV infection.
Psoriasis: HIV can trigger or exacerbate the condition (Image: Dr Sara Ritchie)
Psoriasis typically improves with HAART,32 but in HIV patients whose psoriasis remains moderate or severe, therapy can be challenging.
Conventional systemic immunosuppressant treatments may be contraindicated. Acitretin may be effective and the biologics may be promising therapeutic agents.26
Cutaneous vasculitides are a rare but important manifestation of HIV infection, and may have infective, inflammatory or immunological aetiologies.
A wide spectrum of types of vasculitides can occur, involving small, medium or large vessels, and reflecting almost every pattern and type of vasculitis.33 The hypersensitivity vasculitis Henoch-Schönlein purpura is also seen with other viruses, such as herpes and hepatitis B, although it can occur in HIV infection.34,35 An infective aetiology should always be considered, as well as a HAART-induced hypersensitivity vasculitis, but once these are excluded, the vasculitis can be classified according to the histological pattern. Inflammatory markers can be initially normal, and the gold standard for diagnosis is histopathology.
Vasculitis: a rare but important manifestation of HIV (Image: Dr Gabriela Jimenez Diaz)
Erythema elevatum diutinum is a rare, chronic form of immune-complex mediated cutaneous leukocytoclastic vasculitis, which can occur in association with HIV.36 It is characterised by violaceous papules, plaques or nodules, which may be distributed symmetrically on the extensor surfaces of acral sites. In the context of HIV, it must be distinguished from Kaposi’s sarcoma or bacillary angiomatosis. Histology is diagnostic. Treatment is with oral dapsone, as well as HAART.
Severe xerosis, or dry skin, is more common in HIV patients than in controls. Prevalence figures vary, although it may affect up to almost half of these patients.37 Xerosis is increasingly frequent in more advanced disease, and there is an association with indinavir use. There is little association with atopic disease.
Xerosis: more common in patients with HIV infection (Image: Dr Gabriela Jimenez Diaz)
Changes in cutaneous innervation in HIV infection have now been found, which may be implicated in the development of xerosis.38 Therapy consists of regular emollients.
- Dr Sara Ritchie is clinical assistant in dermatology with Communitas clinics and honorary clinical fellow emeritus in tropical dermatology at University College London Hospitals NHS Foundation Trust
Competing interests: None declared
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16. Olsen CM, Knight LL, Green AC. Risk of melanoma in people with HIV/AIDS in the pre- and post-HAART eras: a systematic review and meta-analysis of cohort studies. PLoS One 2014; 9(4): e95096.
17. D’Souza G, Wiley DJ, Li X et al. Incidence and epidemiology of anal cancer in the multicentre AIDS cohort study. J Acquir Immune Defic Syndr 2008; 48(4): 491-9.
18. Pappert A, Grossman M, DeLeo V. Photosensitivity as the presenting illness in four patients with human immunodeficiency viral infection. Arch Dermatol 1994; 130(5): 618-23.
19. Bilu D, Mamelak AJ, Nguyen RHN et al. Clinical and epidemiologic characterization of photosensitivity in HIV-positive individuals. Photodermatol Photoimmunol Photomed 2004; 20: 175-83.
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33. Guillevin L. Vasculitides in the context of HIV infection. AIDS 2008: 22: S27-33.
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