Diffuse Erythematous Skin Lesions in HIV

Clinical Approach: Key Diagnostic Anchors

1. Acute HIV Seroconversion Exanthem

• Morphology: Diffuse, non-pruritic maculopapular erythematous eruption on face, trunk, palms, and soles
• Associations: Fever, pharyngitis, lymphadenopathy, myalgias/arthralgias, mucosal ulcers (oral/genital)
• Differential: Drug eruption, secondary syphilis, EBV/CMV exanthem
• Diagnosis: HIV RNA viral load (very high), p24 antigen; antibody tests may still be negative
• Harrison's 22E, p. 445

2. Morbiliform (Measles-like) Maculopapular Rash — Differential by Morphology

• Acute retroviral syndrome (most common)
• Drug reaction (especially abacavir, nevirapine, NNRTIs)
• Secondary syphilis — always keep in differential for diffuse erythematous rash

3. Drug Hypersensitivity Reactions

• Abacavir (NRTI): Hypersensitivity in ~5% of patients; fever + rash + GI upset. Life-threatening on re-challenge. Associated with HLA-B*57:01 — screen before prescribing. - Lippincott Pharmacology
• Nevirapine, efavirenz: Maculopapular rash in 15–30%; can progress to SJS/TEN
• Sulfonamides (e.g., TMP-SMX for PCP prophylaxis): Rash in up to 60% of HIV patients
• Rash may be morbiliform or erythrodermic (>90% body surface area involvement)

4. Seborrheic Dermatitis

• Morphology: Erythematous, scaly/greasy patches on face (nasolabial folds, eyebrows, scalp), upper chest
• In advanced HIV: diffuse involvement across the trunk and extremities
• Pathogenesis: Malassezia spp. overgrowth in setting of immune dysregulation
• Treatment: Topical antifungals (ketoconazole shampoo/cream), low-potency topical steroids, calcineurin inhibitors; treat underlying HIV
• Fitzpatrick's Dermatology, p. 3151

5. Psoriasis

• Most common variant in HIV: plaque psoriasis (erythematous, well-demarcated plaques with silvery scale on extensors)
• HIV-specific variants: erythrodermic psoriasis (particularly in sub-Saharan Africa), rupioid psoriasis, palmoplantar involvement (keratoderma blennorrhagica)
• Paradoxically worsens despite CD4 depletion; may flare with IRIS
• Treatment: Topical (mild) → phototherapy (moderate) → acitretin → ART (first-line for moderate-severe); biologics used very cautiously due to immunosuppression risk
• Fitzpatrick's Dermatology

6. Eosinophilic Folliculitis (EF)

• CD4 typically < 250–300 cells/mm³
• Morphology: Intensely pruritic, follicle-centered erythematous papules/pustules on the midline — face, scalp, neck, upper trunk
• Distinct from bacterial folliculitis; biopsy shows eosinophilic infiltration
• Treatment: ART is first-line; symptomatic relief with antihistamines, topical steroids, phototherapy (UVB), itraconazole

7. Papular Pruritic Eruption (PPE)

• More common in tropical/subtropical HIV populations; CD4 < 200
• Morphology: Pruritic, symmetric erythematous papules — predominantly on distal extremities (unlike EF)
• Likely represents hypersensitivity to insect bites in the setting of immune dysregulation
• Treatment: ART; topical steroids, antihistamines, UVA/UVB phototherapy

8. Secondary Syphilis

• Polymorphic rash: macules, papules, targetoid lesions on trunk, palms, soles
• May be atypical and more florid in HIV — shown in the image below
• Diagnose with RPR/VDRL + confirmatory FTA-ABS or TPPA
• Treatment: Benzathine penicillin G

9. Norwegian (Crusted) Scabies

• Occurs with severe immunosuppression
• Morphology: Erythroderma (diffuse erythema + hyperkeratotic scale), especially hands, feet, scalp, face; highly contagious
• Differs from classic scabies by massive mite burden (millions vs. 10–15)
• Treatment: Ivermectin + topical permethrin; isolation

10. Kaposi Sarcoma (KS)

• AIDS-defining; caused by HHV-8 (KSHV); CD4 typically < 200
• Morphology: Red-to-violaceous/brown macules, papules, and plaques — may be widespread and erythematous in early stages
• Favors face, lower extremities, mucosal surfaces
• Diagnosis: Skin biopsy (spindle cells, slit-like vascular spaces)
• Treatment: ART (lesions may regress); chemotherapy (liposomal doxorubicin) for extensive disease

11. Immune Reconstitution Inflammatory Syndrome (IRIS)

• Occurs in up to 20% of patients starting ART, typically within the first 2–3 months
• Previously subclinical infections or dermatoses "unmask" or paradoxically worsen
• Cutaneous manifestations: eosinophilic folliculitis flares, molluscum, herpes, KS, psoriasis
• Management: Continue ART; prednisone 1 mg/kg (taper) for significant reactions; avoid steroids in KS-IRIS
• Fitzpatrick's Dermatology, p. 141

12. Other Causes by Morphology

Diagnostic Algorithm

Diffuse erythematous rash in HIV patient
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1. Check CD4 count + viral load + ART history
2. Drug history — new medication in last 1–8 weeks?
3. Morphology classification (morbiliform, follicular, erythrodermic)
4. Always obtain RPR/VDRL (syphilis)
5. Skin biopsy if diagnosis unclear
6. Culture/PCR if infectious etiology suspected