What are the potential causes and treatments for itching of the hands and feet in a patient taking antiviral medications, such as oseltamivir (antiviral), ribavirin (antiviral), or acyclovir (antiviral), and how can it be managed?

Management of Itching of Hands and Feet After Antiviral Use

Immediate Assessment: Rule Out Severe Reactions First

The most critical first step is to immediately assess for severe cutaneous adverse reactions requiring drug discontinuation: check for mucosal involvement, blistering, skin exfoliation, fever >39°C, or systemic symptoms, as these mandate immediate cessation of the antiviral and urgent medical evaluation. 1, 2

Red Flags Requiring Immediate Drug Discontinuation:

• Mucosal involvement (oral, ocular, genital lesions) 1, 2
• Any blistering or epidermal detachment 1, 2
• Fever exceeding 39°C 1, 2
• Systemic symptoms including lymphadenopathy, hepatitis, or eosinophilia suggesting DRESS syndrome 2
• Intolerable pruritus despite symptomatic treatment 1

Most Likely Diagnosis: Drug-Induced Pruritus

Antivirals can cause pruritus through multiple mechanisms, either as isolated itching without rash or as part of a drug hypersensitivity reaction. 3, 4 The localization to hands and feet suggests either a localized drug reaction or neuropathic component. 5

Management Algorithm

Step 1: Determine Severity and Continue or Stop Antiviral

If no red flags are present and itching is mild to moderate without systemic symptoms, continue the antiviral with aggressive symptomatic management. 3 However, if the causative drug can be identified and safely discontinued without compromising treatment of the underlying viral infection, discontinuation is the definitive treatment. 3

Step 2: First-Line Symptomatic Treatment

• Apply emollients liberally and frequently to the affected areas - this is the cornerstone of topical management for drug-induced pruritus 6, 7, 8
• Use urea-containing or polidocanol-containing lotions specifically for pruritus relief 6
• Prescribe oral H1-antihistamines such as cetirizine, loratadine, or fexofenadine for grade 2/3 pruritus 6, 7
• Avoid hot water exposure and excessive soap use, which worsen xerosis and itching 6

Step 3: Escalate if No Response After 2 Weeks

If itching persists despite emollients and antihistamines:

• Add topical corticosteroids (prednicarbate cream 0.02% or equivalent moderate-potency steroid) to affected areas 6, 2
• Consider menthol-containing coolants for additional symptomatic relief 7, 8
• Reassess for development of any red flag symptoms 6, 1

Step 4: Consider Alternative Systemic Agents for Refractory Cases

For persistent pruritus unresponsive to standard measures:

• Gabapentin may be effective for neuropathic-type itch 6, 7
• Mirtazapine has antipruritic properties through multiple mechanisms 6, 7
• Avoid sedating antihistamines in elderly patients due to fall and cognitive impairment risk 2

Critical Pitfalls to Avoid

• Never use prophylactic corticosteroids or antihistamines when initiating or restarting antivirals - this does not prevent reactions and may increase rash incidence 6, 1, 2
• Never rechallenge with the same antiviral if it caused a severe hypersensitivity reaction 2
• Do not delay recognition of severe reactions - constitutional symptoms or mucosal involvement require immediate evaluation 1, 2
• Avoid topical antivirals for drug-induced pruritus - they are ineffective and not indicated 1

Monitoring and Follow-Up

• Monitor weekly if symptoms are moderate (Grade 2) until improvement to mild (Grade 1) 2
• Instruct patients to return immediately if fever develops, new systemic symptoms appear, or skin lesions worsen 1, 2
• Refer to dermatology urgently if no response after 2 weeks of appropriate treatment, diagnostic uncertainty exists, or rash progresses despite management 2

Context-Specific Considerations

The specific antiviral matters less than the clinical presentation. While antiretrovirals (particularly NNRTIs like nevirapine) have well-documented high rates of severe cutaneous reactions 6, common antivirals like acyclovir, valacyclovir, and oseltamivir can also cause pruritus. 3, 4 The management approach remains the same regardless of the specific agent: assess severity, provide symptomatic relief, and discontinue only if severe features develop or the drug is not essential. 3