Dermatology in HIV

Meet the patient

A 28-year-old man presents with shingles across two dermatomes, oral thrush that will not clear, and a severe, greasy seborrhoeic dermatitis covering his chest. None of these is rare in isolation — but all three together, in a young adult, is the skin shouting the diagnosis.[1]

The two questions that organise everything below: what is the CD4 count? and is the patient on effective ART? The skin is a near-direct readout of immune competence, so once you can place a patient on the CD4 ladder you can predict the eruption, the organism, and the treatment.[1][2]

Why the skin declares the diagnosis first

Over 90 percent of untreated people living with HIV develop at least one dermatological condition, and in roughly a third a skin complaint is the presenting symptom. A severe, atypical, or treatment-resistant eruption is often the event that triggers HIV testing.[1]

The skin is frequently the first organ system to declare the diagnosis because mucocutaneous Langerhans cells are themselves targets of HIV, and the character of the eruption is a near-direct readout of the degree of immune compromise. As the CD4 count falls, common dermatoses become more severe and atypical, opportunistic infections emerge, oncogenic viruses find permissive tissue, and inflammatory pathways become dysregulated.[1][2]

Combination antiretroviral therapy (ART) has transformed the landscape. Many classic HIV dermatoses are now seen only in late presenters, in those with untreated or resistant virus, or as paradoxical immune phenomena — the immune reconstitution inflammatory syndrome (IRIS) — in the first weeks of treatment.[1][5]

[1]

The CD4-stratified spine — the organising principle

Learn the CD4 ladder and you can predict the eruption before you examine the patient. An examiner may ask either "what are the cutaneous neoplasms of HIV?" or "what skin diseases occur at a CD4 of 300?" — the ladder answers both.[1]

[1] [2]

Etymology for viva gold: the word syndrome is Greek for "running together" — and no disease makes signs run together quite like HIV. The same patient may carry candidiasis, molluscum, KS and a chronic herpetic ulcer at one examination.[1]

Two axes of classification

HIV skin disease is classified along two intersecting axes — aetiology and immune stage. Both must be mastered.[1]

[1]

AIDS-defining cutaneous conditions

By CDC criteria, these skin presentations in an HIV-positive patient are themselves AIDS-defining: Kaposi sarcoma, chronic (over 1 month) or disseminated HSV or VZV ulcers, and certain disseminated fungal infections (extrapulmonary histoplasmosis, coccidioidomycosis, disseminated cryptococcosis).[3][14]

Epidemiology & Risk Factors

Several epidemiological truths make HIV skin disease exam-worthy and clinically central.[1]

Skin disease is the rule, not the exception. Before ART, more than 90 percent of HIV-infected individuals developed cutaneous manifestations, and multiple simultaneous dermatoses are typical at low CD4 counts — candidiasis, seborrhoeic dermatitis, molluscum and KS all at once.[1]

ART has changed everything. Effective therapy dramatically reduces the incidence and severity of most HIV-associated dermatoses by restoring CD4 counts. Conditions that were once near-universal in advanced disease — eosinophilic folliculitis, oral hairy leukoplakia, disseminated molluscum, chronic herpetic ulcers — are now comparatively rare in well-treated populations.[2]

Two countervailing trends have emerged: an increase in drug eruptions (more patients on ART, cotrimoxazole prophylaxis, and antibiotics) and the appearance of IRIS as a new clinical entity.[5]

The strongest risk factor for any given HIV dermatosis is the CD4 count. Other risk factors include untreated high viral load, ART non-adherence or virological failure, concomitant STIs (HSV-2, syphilis), chronic immunosuppression, and tropical residence.[1]

[1]

Pathophysiology — three convergent mechanisms

HIV produces skin disease through three convergent mechanisms, and each predicts which condition will appear at which stage.[1]

1. Quantitative immune deficiency (CD4 depletion). HIV binds CD4 and the CCR5 or CXCR4 co-receptor on T-helper cells and mucocutaneous Langerhans cells, destroying the CD4 pool through direct cytopathic effects, syncytium formation, apoptosis, pyroptosis and cytotoxic-T-cell killing. As the absolute CD4 count falls, cell-mediated immunity is progressively lost — the principal defence against intracellular pathogens (mycobacteria, fungi, herpesviruses) and the surveillance mechanism that holds oncogenic viruses in check. The lower the CD4, the more unusual and severe the pathogen.[1][2]

2. Qualitative immune dysregulation (the Th1-to-Th2 shift). Even before profound CD4 depletion, HIV produces a skew from Th1 (cell-mediated) toward Th2 (humoral and eosinophilic) immunity. This shift, with polyclonal B-cell activation, is the engine behind the "idiopathic" HIV dermatoses — most notably eosinophilic folliculitis and the pruritic papular eruption of HIV (PPE), both intensely pruritic and driven by eosinophilic infiltration.[12]

3. Epidermal barrier dysfunction. HIV-infected skin is constitutionally dry (xerosis) with altered lipid composition, microbial dysbiosis with increased Staphylococcus aureus colonisation, and impaired antimicrobial peptide production. This barrier failure explains the severity of seborrhoeic dermatitis, the frequency of staphylococcal folliculitis, and the intractable pruritus of late-stage disease.[1]

A fourth mechanism — oncogenesis — operates through the permissive effect of immunosuppression on oncogenic viruses: HHV-8 drives Kaposi sarcoma; HPV drives squamous cell carcinoma and anal intraepithelial neoplasia; EBV drives oral hairy leukoplakia and certain lymphomas.[3][13]

Clinical Presentation — the CD4 ladder in practice

Acute HIV seroconversion illness

Acute (primary) HIV produces a mononucleosis-like illness two to four weeks after acquisition, lasting one to two weeks. The cutaneous hallmark is a morbilliform (measles-like) rash on the trunk, with fever, lymphadenopathy, pharyngitis, arthralgia and mucosal ulcers.[1]

The rash is easily missed or misattributed — to glandular fever (EBV), a drug reaction, rubella, or secondary syphilis — and is one of the highest-yield exam stems because recognising it allows diagnosis at the most infectious stage. Diagnosis at seroconversion requires an HIV RNA (viral load) PCR (positive) with a negative or indeterminate antibody test (the "window period").[1]

Early disease (CD4 above 500) — common dermatoses behaving badly

The earliest cutaneous markers of HIV are common dermatoses behaving badly. Seborrhoeic dermatitis is the single most common HIV-related dermatosis and may be severe, extensive, treatment-resistant and atypical (chest, axillae, groin rather than just scalp and nasolabial folds).[1]

Recurrent orolabial and anogenital HSV, multidermatomal or early-onset herpes zoster (shingles in a young person is an HIV red flag), recurrent oral candidiasis, extensive or treatment-resistant warts, and florid acne or folliculitis should each prompt HIV testing.[2]

Moderate immunosuppression (CD4 200 to 500) — the pathognomonic dermatoses

As the CD4 crosses below 500 toward 200, the pathognomonic HIV dermatoses emerge.[1]

• Oral hairy leukoplakia (OHL): white, corrugated, non-scrapable plaques on the lateral border of the tongue; caused by EBV; pathognomonic for HIV.[13]
• Kaposi sarcoma (KS): purple-brown to dark red papules, nodules and plaques; AIDS-defining; see below.
• Eosinophilic folliculitis: intensely pruritic, urticarial, follicular papules on the face, neck and upper trunk; HIV-specific; eosinophilia common.[12]
• Molluscum contagiosum: numerous, large (over 1 cm), atypical lesions; may be giant or facial and refractory.
• Psoriasis: may be severe, erythrodermic, or first appear with HIV; may paradoxically flare on ART (IRIS).[1]
• Bacillary angiomatosis: vascular red-purple papules and nodules caused by Bartonella; mimics KS.[9]
• Immune thrombocytopenia (ITP): petechiae and ecchymoses from anti-platelet antibodies.

Severe immunosuppression (CD4 below 200) — the life-threatening entities

Below 200, all moderate-stage conditions persist and worsen, and new life-threatening entities appear.[1]

• Chronic ulcerative HSV or VZV: herpetic ulcers that are chronic, deep, non-healing and often perianal, penile or orofacial; ulceration persisting over 1 month is AIDS-defining.[14]
• Disseminated fungal infections: cryptococcosis (umbilicated papules mimicking molluscum on the face, often with meningitis); histoplasmosis (ulcerated nodules, oral ulcers, petechiae); coccidioidomycosis (nodules, verrucous plaques); Talaromyces (Penicillium) marneffei (umbilicated papules in South-East Asia).[10][15]
• Crusted (Norwegian) scabies: hyperkeratotic, scaly, heavily crusted plaques teeming with millions of mites; highly contagious; an institutional outbreak risk.[11]
• Giant molluscum contagiosum: lesions over 1 cm, confluent, facial; refractory.
• Bacillary angiomatosis: may be disseminated with bacteraemia and visceral (hepatic, splenic) peliosis.[9]

Very severe immunosuppression (CD4 below 50) — mycobacteria and CMV

At the lowest CD4 counts, the patient is prey to disseminated mycobacteria and CMV.[1]

• Disseminated Mycobacterium avium complex (MAC): skin lesions are rare but the systemic illness dominates — fever, weight loss, night sweats, diarrhoea, anaemia.
• Major aphthous ulcers: large (over 1 cm), deep, painful oral and oropharyngeal ulcers; distinguished from HSV by negative viral testing; refractory disease responds to topical or intralesional corticosteroids, thalidomide 50 to 200 mg daily, or dapsone.[2]
• Cytomegalovirus (CMV): cutaneous ulcers (perianal, peristomal, digital) usually with retinitis or colitis.
• Disseminated mycobacteria and aggressive deep fungi: non-tuberculous mycobacteria may produce scattered nodules, abscesses and ulcerations.[1]

Differential Diagnosis — the four highest-yield distinctions

The four highest-yield dermatological distinctions in HIV are each a classic exam stem.[1]

[1]

The discriminator line for the mouth: candidiasis scrapes off; hairy leukoplakia does not. The bedside gauze-wipe test settles it. For the purple papule, the discriminator is the biopsy — Warthin-Starry black bacilli means Bartonella; HHV-8 spindle cells means KS.[9]

[1]

The classic trap: disseminated cryptococcosis produces umbilicated, translucent papules on the forehead and face that can be indistinguishable from molluscum contagiosum. Biopsy with PAS/GMS stain and serum cryptococcal antigen resolve it — and the stakes are high because cutaneous cryptococcosis usually signals disseminated disease with cryptococcal meningitis.[10]

Specific Subtypes — Infections

Viral infections

Herpes simplex virus (HSV). In HIV, HSV runs an atypical course — chronic, deep, ulcerative, often perianal or penile, sometimes verrucous rather than classic grouped vesicles. The cardinal exam point: mucocutaneous HSV ulceration persisting over 1 month is an AIDS-defining illness.[14]

Diagnosis is clinical with PCR or viral culture confirmation. Treatment is oral valaciclovir 500 mg to 1 g twice daily or aciclovir 400 mg five times daily for 7 to 10 days; severe, extensive or resistant disease needs IV aciclovir 5 to 10 mg/kg every 8 hours, and resistant (thymidine-kinase-negative) strains require foscarnet.[2]

Varicella zoster virus (VZV). Herpes zoster in a young adult is an HIV red flag. In advanced HIV, zoster may be multidermatomal, disseminated, haemorrhagic or chronic, with intractable post-herpetic neuralgia. Treat with oral valaciclovir 1 g three times daily for 7 days for uncomplicated disease and IV aciclovir 10 mg/kg every 8 hours for disseminated or severe disease.[1]

Molluscum contagiosum. A poxvirus producing umbilicated pearly papules. In HIV the lesions are numerous, large (giant, over 1 cm), confluent and facial, and may be refractory to standard destructive therapy. Differential includes cryptococcosis and KS. Treatment: curettage, cryotherapy, topical podophyllotoxin, imiquimod, or cantharidin — but the definitive treatment is ART, with which lesions usually resolve as immunity recovers. Refractory disease has responded to cidofovir.[2]

Cytomegalovirus (CMV). Cutaneous CMV is a disease of very low CD4 (below 50), producing painful ulcers (perianal, peristomal, digital) usually in a patient with CMV retinitis or colitis. Diagnosis needs biopsy with owl-eye intranuclear inclusions; treatment is IV ganciclovir or foscarnet.[1]

Human papillomavirus (HPV). Extensive, refractory and atypical warts, condylomata, and HPV-driven intraepithelial neoplasia are common. High-risk HPV-16 and 18 drive anal intraepithelial neoplasia (AIN) and cervical intraepithelial neoplasia, which progress to invasive squamous carcinoma at increased rates — particularly in MSM. This is the rationale for anal Pap screening and high-resolution anoscopy in at-risk patients.[1]

Fungal infections

Oral and oesophageal candidiasis. Candidiasis (usually Candida albicans) is the most common oral manifestation of HIV. Pseudomembranous (thrush — white scrapable plaques), erythematous (red patches), angular cheilitis and atrophic forms occur. Oesophageal candidiasis is AIDS-defining. Treatment: mild disease with oral nystatin suspension or clotrimazole troches; moderate with oral fluconazole 100 to 200 mg daily for 7 to 14 days; oesophageal or refractory with fluconazole 200 to 400 mg daily or IV echinocandin.[2]

Dermatophytosis and onychomycosis. More extensive, atypical (proximal subungual onychomycosis is suggestive of HIV) and treatment-resistant.[1]

Disseminated deep mycoses — AIDS-defining and dangerous. Cryptococcus neoformans produces umbilicated, translucent, gelatinous papules on the forehead, face and neck that mimic molluscum; cutaneous cryptococcosis implies dissemination and mandates a lumbar puncture to exclude cryptococcal meningitis and serum cryptococcal antigen testing; treatment is IV liposomal amphotericin B plus flucytosine for induction then fluconazole consolidation.[10]

Histoplasma capsulatum produces ulcerated nodules, oral ulcers, a papular or acneiform eruption, petechiae and molluscum-like lesions, particularly in the Americas; cutaneous disease implies disseminated histoplasmosis and is treated with amphotericin B then itraconazole.[15]

Bacterial infections

Bacillary angiomatosis (Bartonella henselae or B. quintana). A vascular proliferative disorder unique to immunocompromised hosts (chiefly advanced HIV) producing friable red to purple papules, nodules and angiomatous plaques that closely mimic Kaposi sarcoma. Disseminated disease produces hepatic and splenic peliosis with bacteraemia.[9]

The distinction from KS rests on biopsy: bacillary angiomatosis shows lobular capillary proliferations with neutrophils and a Warthin-Starry stain revealing black-staining bacilli; KS shows spindle cells and HHV-8 positivity. Treatment is oral erythromycin 500 mg four times daily or doxycycline 100 mg twice daily for at least 3 months.[9]

Syphilis. HIV alters the natural history: the rash of secondary syphilis may be atypical or florid, serology may be unreliable (the prozone phenomenon giving false-negatives), and there is accelerated progression to neurosyphilis and ocular syphilis. Because syphilis and HIV are co-transmitted, all patients with syphilis should be HIV-tested and vice versa.[16]

Treatment is standard penicillin-based therapy but with a low threshold for a lumbar puncture to exclude neurosyphilis.[16]

Staphylococcal infections (folliculitis, impetigo, ecthyma, botryomycosis) are common and severe due to high S. aureus colonisation. Mycobacteria — both TB (scrofuloderma, disseminated) and non-tuberculous — produce ulcers, nodules and scattered lesions, especially at very low CD4.[1]

Parasitic infestations

Crusted (Norwegian) scabies. Hyperinfestation with Sarcoptes scabiei producing thick, hyperkeratotic, scaly, grey crusted plaques over the hands, feet, scalp and extensor surfaces. The patient harbours millions of mites, is extraordinarily contagious, and may not complain of intense itch (the immune response that drives pruritus is blunted).[11]

It is a public-health emergency requiring isolation, topical permethrin 5 percent applied head-to-toe repeated weekly, oral ivermectin 200 micrograms/kg on days 1, 2, 8, 9, 15, and 22, and treatment of all contacts and healthcare workers.[11]

Specific Subtypes — Neoplasms

Kaposi sarcoma (KS)

Kaposi sarcoma is an AIDS-defining, HHV-8-driven vascular tumour and the single most examined neoplasm in HIV dermatology.[3]

[3]

Clinical features. Purple, brown, dark red or violaceous macules, papules, plaques and nodules, which may be oedematous (reflecting lymphatic involvement) and may coalesce. Characteristic sites are the lower extremities (classic), the hard palate (highly suggestive in HIV), the face, the genitalia and the trunk. A palatal lesion is almost pathognomonic for epidemic KS.[3]

Diagnosis. Skin biopsy is diagnostic: proliferating spindle cells forming slit-like vascular spaces, with extravasated erythrocytes, haemosiderin and a variable inflammatory infiltrate. HHV-8 immunohistochemistry is positive. Staging assesses visceral involvement (GI endoscopy, chest imaging).[3]

Treatment. For limited cutaneous disease in a treatment-naive patient, ART alone is often sufficient — immune restoration leads to regression. For localised symptomatic lesions, intralesional chemotherapy, cryotherapy or local radiotherapy. For extensive cutaneous, progressive or visceral disease, systemic chemotherapy with pegylated liposomal doxorubicin 20 mg/m2 every 3 weeks, or paclitaxel is first-line.[4]

The key management principle: optimise ART first, since untreated HIV drives KS and IRIS may flare it.[4]

Non-melanoma skin cancer, melanoma and lymphoma

Immunosuppression increases the risk of squamous cell carcinoma (SCC), which in HIV is more often HPV-driven, arises in anogenital and sun-exposed skin, and runs a more aggressive course with higher metastatic potential. Basal cell carcinoma shows a modest increase; melanoma behaves more aggressively with reduced survival. Cutaneous lymphomas (T-cell and B-cell) and CD30-positive anaplastic large cell lymphoma occur at increased rates.[1]

Anal intraepithelial neoplasia (AIN) and invasive anal SCC, driven by HPV-16, are markedly increased in HIV-positive MSM and are screened for with anal cytology.[1]

Specific Subtypes — Inflammatory Dermatoses

Seborrhoeic dermatitis is the commonest HIV dermatosis — greasy yellow scale and erythema on the scalp, nasolabial folds, eyebrows, ears, chest and groin, but in HIV severe, extensive, treatment-resistant and atypical. Treat with topical ketoconazole 2 percent shampoo/cream and a mild topical corticosteroid; recalcitrant disease responds to oral itraconazole or fluconazole and to ART.[1]

Psoriasis may be severe, pustular or erythrodermic, and may first appear with HIV or paradoxically flare on ART (IRIS). Treatment is challenging because traditional systemic immunosuppressants carry added infection risk; phototherapy (NBUVB) is effective and safe, and biologics (anti-TNF, anti-IL-17, anti-IL-23) are increasingly used with ART optimisation.[1]

Eosinophilic folliculitis is an HIV-specific, intensely pruritic eruption of urticarial follicular papules and pustules on the face, neck, upper trunk and extensor arms. Histology shows a perifollicular eosinophil-rich infiltrate; peripheral eosinophilia is common. It typically appears at CD4 of 200 to 300. Treatment: topical corticosteroids, antihistamines, phototherapy (NBUVB), topical permethrin, and in resistant cases oral isotretinoin or itraconazole — ART is the most effective long-term therapy.[12]

Pruritic papular eruption of HIV (PPE) is chronic, intensely pruritic, symmetric papules and excoriated nodules on the extremities and trunk, driven by an eosinophilic response. Distinct from scabies (no burrows, negative scrapings) and eosinophilic folliculitis (not folliculocentric). Treat with antihistamines, topical corticosteroids, phototherapy and ART.[12]

Acne and folliculitis are often severe; atopic dermatitis may flare; xerosis and acquired ichthyosis are common and contribute to intractable pruritus in late disease.[1]

Drug Eruptions — 10 to 100 times more common

Drug eruptions are dramatically more common in HIV — a 10 to 100-fold increased risk — reflecting immune dysregulation, polypharmacy, slow drug metabolism, and the specific immune-activating effects of several antiretrovirals and cotrimoxazole.[2]

Cotrimoxazole (TMP-SMX) is the single most common culprit, used for Pneumocystis prophylaxis. Morbilliform maculopapular rash with fever occurs in roughly 40 to 60 percent of HIV patients (versus around 3 percent of the general population). Most cases are mild and resolve or can be managed with desensitisation, but SJS/TEN can occur. Alternatives: dapsone, atovaquone or aerosolised pentamidine.[2]

Abacavir (an NRTI) causes a characteristic systemic hypersensitivity reaction (fever, rash, GI symptoms, malaise, respiratory symptoms) within the first 6 weeks. It is HLA-B*5701-restricted, and all patients must be screened for HLA-B*5701 before starting abacavir — if positive, abacavir is contraindicated and never rechallenged (re-exposure can cause fatal anaphylaxis).[7]

The classic trap: nevirapine carries a high risk of SJS/TEN, greatest in women with CD4 above 250 cells/microL (and men above 400) — for this reason nevirapine is avoided in these groups and a lead-in dose escalation is used.[8]

Efavirenz causes a mild maculopapular rash and characteristic neuropsychiatric symptoms (vivid dreams, insomnia, anxiety, depression) that usually settle within weeks. Tenofovir, zidovudine, lamivudine, dolutegravir and raltegravir are comparatively benign cutaneously.[2]

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS is the paradoxical worsening of an existing condition, or the unmasking of a subclinical infection, within weeks to months of starting ART — as recovering immunity mounts an exaggerated inflammatory response to antigens that were previously "quiet."[5]

Risk factors: a low baseline CD4 count (the single strongest predictor), a high CD4 rise or viral load fall after ART, a short interval between treating an opportunistic infection and starting ART, and an unrecognised opportunistic infection at ART initiation.[5]

Cutaneous IRIS produces a flare of pre-existing dermatoses or the unmasking of occult infection:[5]

• KS-IRIS: rapid enlargement, oedema and visceral progression of Kaposi sarcoma in the first weeks of ART — can be life-threatening if visceral.
• Acne or folliculitis flare (sometimes severe cystic acne).
• Worsening psoriasis or first presentation of severe psoriasis.
• Unmasking of previously subclinical infection: cryptococcosis (with meningitis), MAC, mycobacterial disease, HSV/VZV reactivation.
• Severe or refractory molluscum during immune recovery.[1]

Management of IRIS: do NOT stop ART — that is the temptation and the wrong move. Continue ART, treat the unmasked or flared condition specifically, and use systemic corticosteroids (for example oral prednisolone 1 to 2 mg/kg/day tapering) for severe or organ-threatening IRIS. In severe paradoxical reactions to mycobacterial disease, anti-TNF agents such as infliximab and thalidomide have a role.[6]

IRIS versus treatment failure — the critical distinction. Both may produce worsening disease after starting ART. IRIS shows a falling viral load and rising CD4 (the immune system is recovering); treatment failure shows a rising or unsuppressed viral load. A viral load is mandatory before attributing worsening to IRIS.[5]

Clinical & Bedside Assessment

A focused dermatological examination in suspected or known HIV is systematic and exposes the patient fully.[1]

Examine the whole skin, the mucosae and the anogenital area. Inspect the scalp and face (seborrhoeic dermatitis, molluscum, eosinophilic folliculitis, KS, acne), the oral cavity (candidiasis, hairy leukoplakia — lift the tongue to see the lateral border — aphthae, oral KS), the trunk (molluscum, KS, drug rash, syphilis), the flexures and anogenital area (HSV ulcers, condyloma, warts, AIN, crusted scabies), the nails (proximal subungual onychomycosis, periungual warts), and the palms and soles (syphilis, scabies). Palpate the lymph nodes and examine for lymphoedema (KS).[1]

Bedside tests: a KOH preparation distinguishes candidiasis (pseudohyphae) from hairy leukoplakia (negative); a Tzanck smear of a vesicle shows multinucleated giant cells in HSV/VZV; dermoscopy of a suspicious lesion distinguishes a melanocytic from a vascular lesion (KS shows a violaceous homogenous area with rainbow pattern); skin scrapings in mineral oil identify scabies mites; and the simple gauze-wipe test settles the candidiasis-versus-leukoplakia question (candidiasis scrapes off, leukoplakia does not).[1]

Investigations

Skin biopsy is central to confirming KS, bacillary angiomatosis, deep fungal infection, mycobacterial disease, lymphoma and drug eruption. The choice of stain matters: H and E for routine histology; Warthin-Starry stain for Bartonella; PAS and GMS (methenamine silver) for fungi (cryptococcus shows narrow-based budding yeasts with a mucin-positive capsule on mucicarmine); Fite-Faraco for mycobacteria; HHV-8 immunohistochemistry for KS. Culture and PCR of lesions, swabs and blood confirm HSV/VZV, Bartonella, mycobacteria and fungi. Serology (RPR/VDRL plus TPPA for syphilis; cryptococcal antigen) and flow cytometry for lymphoma complete the workup.[1][9]

Baseline HIV staging bloods in any newly-diagnosed patient: CD4 count and percentage, HIV viral load (RNA PCR), full blood count, liver and renal function, HBV and HCV serology, syphilis serology, Toxoplasma IgG, and a tuberculosis screen (IGRA or symptom screen plus chest X-ray). The CD4 count dictates the differential diagnosis and the urgency of ART.[2]

Management — Resuscitation

Most HIV skin disease is not an emergency, but four scenarios are.[1]

SJS/TEN. The defining emergency. STOP the offending drug immediately (nevirapine, cotrimoxazole, abacavir, or any newly-introduced agent), admit to ICU or burns, give intravenous fluids and electrolyte support, wound care, nutritional support, and urgent ophthalmology (ocular adhesions are the leading cause of long-term morbidity). IVIG or ciclosporin may be considered; systemic corticosteroids are controversial.[8]

Disseminated fungal infection with sepsis. Disseminated histoplasmosis, coccidioidomycosis and cryptococcosis may present with cutaneous lesions and septic shock or meningitis — start IV amphotericin B and manage the airway, circulation and meningitis.[10][15]

Crusted scabies outbreak. Isolate the patient, treat with permethrin plus ivermectin, and prophylactically treat all healthcare worker and household contacts, because a missed case can seed a ward-wide outbreak.[11]

Severe IRIS. KS-IRIS with airway compromise or extensive visceral disease, or IRIS with organ failure, needs systemic corticosteroids and specialist input; do not stop ART.[5][6]

Management — Definitive — the five pillars

The management of HIV skin disease rests on five pillars.[1][2]

1. Antiretroviral therapy (ART) — the cornerstone. Effective ART, by restoring CD4 counts and suppressing viral load, resolves the majority of HIV-associated dermatoses and prevents recurrence. The landmark START trial established that ART should be initiated in all patients regardless of CD4 count — "test and treat", with ART started on diagnosis. For a patient presenting with an AIDS-defining cutaneous illness, ART is urgent.[2]

2. Condition-specific dermatological therapy. Each dermatosis is treated in its own right, but ART is added (or optimised) in parallel. The high-yield specifics:[1]

[1]

Phototherapy and physical modalities. Narrowband UVB (NBUVB) is a workhorse in HIV dermatology because it elegantly sidesteps the systemic immunosuppression that complicates HIV. It is first-line or adjunctive for eosinophilic folliculitis, pruritic papular eruption, severe psoriasis, and severe atopic dermatitis in HIV. UVB is not contraindicated in HIV, and it avoids the additive infection risk of methotrexate or ciclosporin. Cryotherapy, curettage and electrodessication manage warts, molluscum and benign lesions.[2]

Symptomatic and supportive therapy. Intractable pruritus — a defining misfeature of late HIV skin disease — is managed with emollients and soap avoidance for xerosis, oral antihistamines (sedating at night such as hydroxyzine 25 to 50 mg), and topical menthol/camphor or capsaicin for neuropathic itch. Thalidomide (50 to 100 mg at night) is highly effective for severe refractory aphthous ulceration but mandates strict contraception and monitoring for peripheral neuropathy.[2]

Follow-up and monitoring. A patient with HIV skin disease is followed jointly with the HIV physician. The CD4 count and viral load are the master variables — a dermatosis that fails to resolve despite specific therapy should prompt a check of virological suppression and ART adherence. Every visit is an opportunity for total-body skin examination (skin cancer surveillance), STI screening, and mental-health and adherence support.[1]

3. Drug-eruption management. Stop the offending drug and document it as an allergy. Screen for HLA-B*5701 before abacavir; avoid nevirapine in women with CD4 above 250; consider cotrimoxazole desensitisation for mild reactions where prophylaxis is essential; switch to an alternative agent guided by an HIV physician.[7][8]

4. IRIS management. Continue ART; treat the unmasked or flared condition; add systemic corticosteroids for severe or organ-threatening IRIS.[5][6]

5. Cancer screening and prevention. Regular total-body skin examination for KS, SCC, BCC and melanoma; anal Pap smear and high-resolution anoscopy for at-risk patients (AIN screening); cervical screening; sun-protection counselling; and HPV vaccination.[1]

The mantra

ART is the single most effective treatment for all HIV skin disease. Everything else is condition-specific and runs in parallel.[2]

Complications & Pitfalls

The commonest diagnostic error is to mistake disseminated cryptococcosis (umbilicated papules) for molluscum contagiosum, delaying lumbar puncture and antifungal therapy with potentially fatal consequences. A second classic error is to confuse bacillary angiomatosis with KS and treat with chemotherapy rather than antibiotics — biopsy with Warthin-Starry stain resolves it.[9][10]

The commonest management error is stopping ART during IRIS — paradoxical worsening is a sign of successful immune recovery and should be managed with corticosteroids, not drug withdrawal. Re-challenging abacavir after a hypersensitivity reaction is potentially fatal and must never be done. Failing to isolate crusted scabies seeds institutional outbreaks.[5][7][11]

Complications of the diseases themselves. Untreated KS produces lymphoedema, pain, visceral (GI bleeding, pulmonary) disease and disfigurement. Chronic herpetic ulcers may become secondarily infected and act as a portal for bacteraemia. Long-standing pruritic papular eruption and eosinophilic folliculitis produce disabling pruritus, sleep deprivation, stigmatisation and depression.[1]

Prognosis & Disposition

The prognosis of HIV skin disease is transformed by effective ART. The majority of inflammatory and infectious dermatoses — seborrhoeic dermatitis, candidiasis, molluscum, eosinophilic folliculitis, oral hairy leukoplakia, chronic herpetic ulcers — resolve or markedly improve as CD4 counts recover. Epidemic KS frequently regresses with ART alone.[2][4]

Disposition. A patient with a new AIDS-defining cutaneous illness (KS, chronic herpetic ulcer, disseminated mycosis) needs urgent HIV physician input, immediate ART initiation, and management of the specific condition. Patients on ART with mild dermatoses are managed as outpatients. Any suspicion of SJS/TEN, disseminated fungal sepsis, or crusted scabies mandates admission. A rising CD4 with paradoxical worsening is IRIS until proven otherwise.[5]

Special Populations

Children with perinatally-acquired HIV frequently present with severe, recurrent candidiasis, extensive warts, refractory molluscum, chronic paronychia and failure to thrive; drug dosing is weight-based and nevirapine-induced SJS is documented in paediatric cohorts.[8]

Pregnant women living with HIV require ART for both maternal health and prevention of mother-to-child transmission; efavirenz is now considered safe in the first trimester, but drug choice must be coordinated with the obstetric and HIV teams. Drug eruptions and IRIS may complicate pregnancy, and untreated syphilis co-infection is catastrophic for the fetus.[2]

Late presenters (CD4 below 200 at diagnosis) bear the full classic dermatological spectrum and are at highest risk of IRIS when ART is started; a period of treatment of active opportunistic infection before ART initiation may reduce IRIS risk in selected cases (for example, TB or cryptococcal meningitis).[5]

Evidence, Guidelines & Regional Differences

The START trial (2015) established that immediate ART (at CD4 above 500) reduces serious AIDS and non-AIDS events and death compared with deferred ART, cementing the "test and treat" strategy and confirming ART as the foundation of management for every HIV dermatosis.[2]

HLA-B*5701 screening before abacavir was validated in the PREDICT-1 randomised study and is now standard of care worldwide; a negative screen essentially abolishes immunologically-mediated abacavir hypersensitivity.[7]

Nevirapine CD4-based prescribing restrictions (avoid in women with CD4 above 250 and men above 400) derive from pivotal cohort data and are embedded in WHO and national guidelines.[8]

[1]

Exam Pearls

Ward-round test

A young man has white corrugated plaques on the lateral tongue that will not scrape off, plus oral thrush that does. Two diagnoses and the organism?

Oral hairy leukoplakia (EBV, non-scrapable, on the lateral tongue border — pathognomonic for HIV) plus oral candidiasis (Candida, scrapable). The gauze-wipe test is the bedside discriminator: thrush comes off, leukoplakia stays. Offer an HIV test. [13][2]

CD4 of 80, umbilicated pearly papules on the forehead, and a low-grade headache. Molluscum — or not?

Not necessarily. Disseminated cryptococcosis produces umbilicated translucent papules that are indistinguishable from molluscum, and the headache signals possible meningitis. Biopsy with PAS/GMS and send serum cryptococcal antigen, then do a lumbar puncture. Treat with liposomal amphotericin B plus flucytosine. Cutaneous cryptococcosis equals disseminated disease. [10]

Three weeks after starting ART, a patient's Kaposi sarcoma lesions enlarge and the leg swells. Viral load is now undetectable. What is happening?

KS-IRIS — paradoxical worsening as immunity recovers. The falling viral load confirms immune recovery, not treatment failure. Do NOT stop ART. Treat with systemic corticosteroids (prednisolone 1 to 2 mg/kg/day tapering) if organ-threatening or severe; involve the HIV team. [5][6]

A woman with CD4 of 300 is started on nevirapine and develops SJS. Why, and what is the rule?

Nevirapine carries high SJS/TEN risk that is greatest in women with CD4 above 250 (and men above 400) — so it is avoided in these groups. STOP the drug immediately, admit to ICU or burns, and never rechallenge. The lesson: check the CD4 before choosing the NNRTI. [8]

References

1. [1]Karadag AS, Elmas ÖF, Altunay İK, et al. Cutaneous manifestations associated with HIV infections: A great imitator Clin Dermatol, 2020.PMID 32513397
2. [2]Mohseni Afshar Z, Goodarzi A, Emadi SN, et al. A Comprehensive Review on HIV-Associated Dermatologic Manifestations: From Epidemiology to Clinical Management Int J Microbiol, 2023.PMID 37496761
3. [3]Cesarman E, Damania B, Krown SE, et al. Kaposi sarcoma Nat Rev Dis Primers, 2019.PMID 30705286
4. [4]Patel R, Lurain K, Yarchoan R, et al. Clinical management of Kaposi sarcoma herpesvirus-associated diseases: an update on disease manifestations and treatment strategies Expert Rev Anti Infect Ther, 2023.PMID 37578202
5. [5]Müller M, Wandel S, Colebunders R, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis Lancet Infect Dis, 2010.PMID 20334848
6. [6]Armange L, Lacroix A, Petitgas P, et al. The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review Eur J Clin Microbiol Infect Dis, 2023.PMID 36795280
7. [7]Waters LJ, Mandalia S, Gazzard B, et al. Prospective HLA-B*5701 screening and abacavir hypersensitivity: a single centre experience AIDS, 2007.PMID 18025891
8. [8]du Toit JD, Kotze K, van der Westhuizen HM, et al. Nevirapine-induced Stevens-Johnson syndrome in children living with HIV in South Africa South Afr J HIV Med, 2021.PMID 33824730
9. [9]Akram SM, Anwar MY, Thandra KC, et al. Bacillary Angiomatosis 2026.PMID 28846267
10. [10]Noguchi H, Matsumoto T, Kimura U, et al. Cutaneous Cryptococcosis Med Mycol J, 2019.PMID 31787730
11. [11]Niode NJ, Adji A, Gazpers S, et al. Crusted Scabies, a Neglected Tropical Disease: Case Series and Literature Review Infect Dis Rep, 2022.PMID 35735761
12. [12]Long H, Zhang G, Wang L, et al. Eosinophilic Skin Diseases: A Comprehensive Review Clin Rev Allergy Immunol, 2016.PMID 25876839
13. [13]Rathee M, Jain P. Hairy Leukoplakia 2026.PMID 32119478
14. [14]Sirka CS Clinical features of a large chronic ulcer on the genital and perianal region in HIV-infected patients can be a strong clinical clue for the diagnosis of herpes simplex infection Indian J Sex Transm Dis AIDS, 2020.PMID 33817593
15. [15]Lin MJ, Mazzoni D, Gin D. Disseminated cutaneous-only histoplasmosis in a patient with AIDS Australas J Dermatol, 2019.PMID 31250916
16. [16]Stefani A, Riello M, Rossini F, et al. Neurosyphilis manifesting with rapidly progressive dementia: report of three cases Neurol Sci, 2013.PMID 24062212