Workup for Viral Exanthem
For suspected viral exanthem, the workup should be primarily clinical based on history and physical examination findings, with laboratory testing reserved for specific clinical scenarios where differentiation from drug hypersensitivity is critical or when specific viral identification would alter management.
Initial Clinical Assessment
The first step is determining whether the rash is truly viral versus drug-induced or bacterial:
- Look for characteristic viral features including conjunctivitis, coryza, cough, diarrhea, hoarseness, or discrete ulcerative stomatitis, which strongly suggest viral etiology over bacterial causes 1, 2
- Assess rash morphology and distribution as most viral exanthems can be distinguished by these features without requiring investigations 3
- Consider patient age as certain exanthems are more common in specific age groups 3
- Evaluate timing of symptom onset relative to any recent medication use, as viral exanthema during concurrent medication use mimics drug allergy in 10% of cases 4
When Laboratory Testing is NOT Needed
In immunocompetent patients with classic viral features and no concerning symptoms, laboratory workup is unnecessary 2, 3. The vast majority of viral exanthems are self-limited and require only symptomatic management with analgesics, antipyretics, hydration, and nutritional support 2.
When Laboratory Testing IS Indicated
Pursue targeted laboratory workup in these specific scenarios:
1. Differentiation from Drug Hypersensitivity
When a patient develops rash while taking medications (especially beta-lactams or NSAIDs) and viral versus drug etiology is unclear 4:
- Serological testing for common viral pathogens: EBV, HHV-6, CMV, and Mycoplasma pneumoniae 4
- PCR assays for viral identification, though a concomitant acute infection does not exclude drug hypersensitivity 4
- Note that skin tests and in vitro tests (basophil activation, lymphocyte transformation) have low sensitivity and specificity 4
2. Suspected Herpes Simplex Virus
If HSV is suspected as the cause 2:
- Consider viral culture or PCR from lesion
- Initiate oral antiviral therapy (acyclovir, valacyclovir, or famciclovir) 2
3. Immunocompromised Patients
Maintain a lower threshold for testing and more aggressive management 2:
- Quantitative EBV DNA PCR from whole blood, plasma, or serum 5
- Complete blood count with differential 5
- Urgent endoscopy with tissue biopsy if GI symptoms present, including EBER in situ hybridization for EBV-PTLD 5
4. Suspected Bacterial Superinfection
If patient fails to respond to supportive care or develops painful lesions, pustules, yellow crusts, or discharge 2:
- Bacterial cultures from lesions
- Administer appropriate antibiotics based on sensitivities 2
Common Pitfalls to Avoid
- Do not routinely order extensive viral panels in immunocompetent patients with classic viral features, as this is not cost-effective and rarely changes management 3, 6
- Do not assume viral exanthem excludes drug hypersensitivity when medications are involved—the distinction during acute phase is often impossible 4
- Do not use antiviral agents for EBV-related exanthems in immunocompetent patients, as they have no proven efficacy 5
- Do not confuse viral exanthem with severe cutaneous adverse reactions (SJS/TEN, DRESS, AGEP)—look for danger signs including vesicles, dusky lesions, painful/burning skin, fever, mucous membrane involvement, or skin detachment 1
Management Based on Findings
- Immunocompetent patients: Symptomatic treatment only with acetaminophen or NSAIDs for fever/pain, adequate hydration, and nutritional support 2
- Immunocompromised patients with EBV-PTLD: Reduce immunosuppression immediately and initiate rituximab 375 mg/m² weekly 5
- HSV-related exanthem: Oral antiviral therapy 2
- Bacterial superinfection: Culture-directed antibiotics 2