Immunology · Year 2 · from Immunology
Case 3: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Patient Demographics
- Age: 55 years old
- Sex: Male
- Ethnicity: African American
Chief Complaint
Fever, rash, and facial swelling 4 weeks after starting allopurinol
History of Present Illness
A 55-year-old man presents with 5 days of fever, progressive rash, and facial swelling. He was started on allopurinol 4 weeks ago for recurrent gout attacks. Five days ago, he developed low-grade fever and a faint rash on his trunk that has progressed to involve his entire body. He reports facial puffiness, especially around his eyes, sore throat, and generalized malaise. He denies dyspnea, cough, or abdominal pain.
Past Medical History
- Gout with recurrent flares
- Hypertension
- Chronic kidney disease stage 3
- Type 2 diabetes
Medications
- Allopurinol 100mg daily (started 4 weeks ago)
- Lisinopril 10mg daily
- Metformin 1000mg twice daily
Physical Examination
- General: Ill-appearing man with prominent facial edema
- Vital Signs: T 39.1C, HR 98, RR 18, BP 135/82
- HEENT: Periorbital and facial edema; pharyngeal erythema; no oral ulcers
- Skin: Diffuse morbilliform eruption with areas of confluence; involving >80% BSA; facial edema; no mucosal involvement; no vesicles or skin sloughing; no Nikolsky sign
- Lymphatics: Cervical, axillary, and inguinal lymphadenopathy
- Abdomen: Hepatomegaly (liver edge 4cm below costal margin); mild RUQ tenderness
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 18,500/uL | 4,500-11,000/uL |
| Eosinophils | 28% (AEC 5,180/uL) | <5% (AEC <500/uL) |
| Atypical lymphocytes | Present | Absent |
| Hemoglobin | 12.8 g/dL | 14-18 g/dL |
| Platelets | 145,000/uL | 150,000-400,000/uL |
| AST | 420 U/L | 10-40 U/L |
| ALT | 510 U/L | 7-56 U/L |
| Alkaline phosphatase | 185 U/L | 44-147 U/L |
| Total bilirubin | 2.1 mg/dL | 0.1-1.2 mg/dL |
| Creatinine | 2.4 mg/dL (baseline 1.8) | 0.7-1.3 mg/dL |
| HHV-6 PCR | Positive | Negative |
Diagnosis
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome due to allopurinol
Discussion
DRESS is a severe cutaneous adverse reaction (SCAR) representing a Type IV hypersensitivity with unique features:
Pathophysiology:
- T cell-mediated drug hypersensitivity
- Delayed onset (2-8 weeks after drug initiation)
- Viral reactivation (HHV-6, EBV, CMV) plays a role in pathogenesis
- HLA associations: HLA-B*58:01 strongly associated with allopurinol-DRESS (especially in Asian populations)
RegiSCAR criteria for DRESS diagnosis:
- Hospitalization required
- Suspected drug reaction
- Fever >38C
- Enlarged lymph nodes
- At least one internal organ involvement
- Blood count abnormalities (eosinophilia and/or atypical lymphocytes)
High-risk drugs for DRESS:
- Allopurinol
- Aromatic anticonvulsants (carbamazepine, phenytoin, lamotrigine)
- Sulfonamides
- Dapsone
- Vancomycin
This patient's features supporting DRESS:
- Latency period: 4 weeks (typical 2-8 weeks)
- Morbilliform rash with facial edema
- Fever, lymphadenopathy
- Eosinophilia with atypical lymphocytes
- Hepatitis (most common internal organ involvement)
- HHV-6 reactivation
Distinguishing DRESS from other severe drug reactions:
| Feature | DRESS | SJS/TEN | AGEP |
|---|---|---|---|
| Onset | 2-8 weeks | 1-3 weeks | 1-2 days |
| Mucosal | Rare | Prominent | Rare |
| Skin | Morbilliform | Blisters, necrosis | Pustules |
| Eosinophilia | Common | Rare | Neutrophilia |
| Organ involvement | Common | Rare | Rare |
Treatment
- Immediate: Stop allopurinol (and any other potential causative drugs)
- Corticosteroids: Prednisone 1-1.5 mg/kg/day for severe disease
- Supportive care: IV fluids, monitoring hepatic and renal function
- Prolonged taper: Steroids over 8-12 weeks (rapid taper risks relapse)
- Monitor for complications:
- Autoimmune sequelae (thyroiditis) can develop weeks to months later
- Fulminant hepatitis (may require consideration of liver transplant)
- Future avoidance: Allopurinol contraindicated; consider febuxostat with caution
- Consider HLA testing: HLA-B*58:01 screening before allopurinol in high-risk populations
- Mortality: 5-10% even with treatment
Important: Resolution is slow; eosinophilia and organ involvement may persist for weeks