What syndrome does the immunocompromised patient with hairy cell leukemia who developed a diffuse rash and low‑grade fever after starting ciprofloxacin have?

DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)

This immunocompromised patient with hairy cell leukemia who developed a diffuse rash and low-grade fever after starting ciprofloxacin most likely has DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms).

Clinical Reasoning

The presentation of diffuse rash with fever in an immunocompromised patient following ciprofloxacin initiation is highly consistent with DRESS syndrome. This diagnosis is supported by:

• Temporal relationship: DRESS typically begins within the first 2 months after drug initiation 1
• Clinical features: The combination of fever, diffuse rash, and the patient's immunocompromised state from hairy cell leukemia creates the classic triad 2
• Known association: Ciprofloxacin is a documented cause of DRESS syndrome, though fluoroquinolones cause delayed maculopapular exanthems in 2-3% of patients 3

Key Diagnostic Features of DRESS

DRESS syndrome presents with characteristic findings that distinguish it from simple drug hypersensitivity 1:

• Acute onset within first 2 months of drug exposure
• Fever (as seen in this patient)
• Severe skin disease with infiltrated papules and facial edema or exfoliative dermatitis
• Lymphadenopathy
• Hematologic abnormalities: hypereosinophilia and atypical lymphocytes
• Organ involvement: hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis
• Mortality rate: approximately 10% 1

Critical Pitfalls in Immunocompromised Patients

The immunocompromised state from hairy cell leukemia creates a diagnostic trap 4. In these patients:

• Classic clinical and histopathological features may be obscured by the impaired immune milieu
• The presentation can mimic tropical fever or other infectious processes 2
• There is profound immune dysfunction predisposing to opportunistic infections, which can confound the clinical picture 4
• Atypical infections must be ruled out before attributing symptoms solely to drug reaction 4

Immediate Management Algorithm

1. Discontinue ciprofloxacin immediately 5, 2
2. Assess for organ involvement: Check liver enzymes, renal function, complete blood count with differential (looking for eosinophilia and atypical lymphocytes)
3. Initiate corticosteroids if organ involvement is present - this provides dramatic improvement 1
4. Rule out concurrent infection: Given hairy cell leukemia, maintain high suspicion for opportunistic infections including non-tuberculous mycobacteria 4

Prognosis and Follow-up

• Complete improvement is usual after drug withdrawal 1
• Relapses may occur even after stopping the offending agent 1, 6
• The signs and symptoms may be indolent and persistent, requiring close observation 6
• When organ involvement exists, corticosteroids are often necessary with dramatic improvement expected 1

Alternative Considerations

While DRESS is most likely, the differential in this immunocompromised patient must include:

• Simple maculopapular exanthem from ciprofloxacin (more common, generally benign and self-limited) 3
• Opportunistic infections given the profound immunosuppression from hairy cell leukemia 4
• Drug-induced hemophagocytic lymphohistiocytosis (rare but reported with antibiotics in hairy cell leukemia patients) 7

The presence of fever with rash rather than rash alone, combined with the immunocompromised state, elevates concern for DRESS over simple drug hypersensitivity.