What is the diagnosis and treatment for a patient with a 3-week history of prolonged fever, headache, and rash, who now presents with a localized rash on one leg, suggestive of acute Human Immunodeficiency Virus (HIV) infection?

Localized Rash 3 Weeks After Fever Resolution: Likely Drug Reaction, Not Acute HIV

This localized unilateral leg rash appearing 3 weeks after fever resolution is most consistent with a delayed drug hypersensitivity reaction, most likely to naproxen or another medication, rather than acute HIV seroconversion illness. 1

Why This is NOT Acute HIV Infection

Timeline Mismatch

• Acute HIV seroconversion rash occurs during the acute febrile illness, not 3 weeks after fever resolution 2, 3, 4
• The typical acute HIV syndrome presents with fever, rash, pharyngitis, and lymphadenopathy occurring simultaneously within the first few weeks after infection 2, 5, 6
• Acute HIV rash appears within 2-4 weeks of infection exposure and resolves as the acute illness resolves 3, 4

Distribution Pattern is Wrong

• Acute HIV rash is characteristically generalized, affecting the trunk, face, and extremities symmetrically 3, 5
• Your unilateral leg-only distribution is atypical for acute HIV and strongly suggests a localized drug reaction or contact dermatitis 1

Temporal Sequence Excludes Acute HIV

• If you had acute HIV infection, the rash would have appeared with the fever 3+ weeks ago, not appearing fresh now after fever resolution 2, 3, 4

Most Likely Diagnosis: Delayed Drug Hypersensitivity

The most probable cause is a delayed cutaneous drug reaction, particularly if you started naproxen or any other medication during or after your febrile illness. 1

Key Features Supporting Drug Reaction

• Delayed drug reactions can occur days to weeks after medication initiation 2, 1
• Localized presentation is consistent with fixed drug eruption or localized hypersensitivity 1
• The timing (3 weeks post-fever) suggests you may have started a medication during your illness that is now causing a reaction 1

Immediate Actions Required

Stop the Offending Agent

• Discontinue naproxen or any NSAIDs immediately and permanently if you have been taking them 1
• Review ALL medications started in the past 4-6 weeks and discontinue the most likely culprit 2, 1

Assess for Severe Reactions (Urgent Evaluation Needed If Present)

• Check for mucosal involvement (mouth, eyes, genitals), blistering, or skin peeling—these indicate Stevens-Johnson syndrome requiring immediate hospitalization 2, 1
• Measure temperature—fever >39°C with rash indicates severe hypersensitivity requiring emergency care 1
• Look for systemic symptoms: new lymph node swelling, jaundice, or organ dysfunction suggesting DRESS syndrome 2, 1

Initial Management for Mild Localized Rash

• Apply moderate-potency topical corticosteroids (triamcinolone 0.1% cream) twice daily to affected areas 1
• Take oral antihistamines (cetirizine 10 mg daily or diphenhydramine 25-50 mg every 6 hours) for itch relief 1
• Use emollients liberally to maintain skin barrier 1

When to Worry About HIV Instead

You should reconsider acute HIV infection ONLY if:

• You had unprotected sexual exposure or needle exposure within 2-6 weeks before your original fever 2
• Your original febrile illness included multiple symptoms: severe sore throat, generalized lymphadenopathy, oral ulcers, generalized rash (not just leg), severe headache 3, 4, 5
• You have ongoing risk factors and the fever-rash syndrome occurred together 3 weeks ago 2, 3

If HIV Testing is Warranted

• Request HIV RNA viral load or HIV DNA PCR—standard antibody tests may still be negative in early infection 2, 6
• Standard rapid HIV antibody tests are often negative during acute infection 2, 6
• Testing should include both HIV antigen/antibody combination test AND HIV RNA if acute infection is suspected 2

Critical Pitfalls to Avoid

• Never use prophylactic corticosteroids or antihistamines when restarting suspected medications—this increases rash incidence and masks severe reactions 2, 1
• Never rechallenge with the suspected drug if it caused a significant rash 2, 1
• Do not ignore fever with rash—this combination requires urgent evaluation for severe drug reactions or systemic illness 1
• Do not assume HIV is ruled out by negative rapid tests if acute infection is suspected—viral load testing is required 2, 6

Follow-Up Plan

• Monitor weekly until rash completely resolves 1
• Seek immediate medical attention if you develop fever, mucosal lesions, blistering, or systemic symptoms 2, 1
• If no improvement after 2 weeks of treatment, obtain dermatology referral for biopsy and definitive diagnosis 1
• Consider complete blood count and liver function tests to rule out systemic involvement if rash persists or worsens 1