DRESS syndrome
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"DRESS syndrome" drug reaction eosinophilia systemic symptoms
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DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)
Also termed Drug-Induced Hypersensitivity Syndrome (DIHS), DRESS is one of the most severe cutaneous adverse drug reactions (SCARs), carrying a mortality of up to 10%.
Definition
DRESS is a severe, immune-mediated adverse drug reaction characterized by the triad of:
- Fever + extensive skin rash
- Hematologic abnormalities (eosinophilia, atypical lymphocytes)
- Internal organ involvement
- Rosen's Emergency Medicine, p. 1899; Tintinalli's Emergency Medicine, p. 1669
Epidemiology & Timing
- Onset typically 2-8 weeks after starting the culprit drug (longer latency than most drug reactions)
- Genetic predisposition plays a role - family members should be counseled when a case is diagnosed
- Incidence varies widely by drug class
- Tintinalli's Emergency Medicine, p. 1668
Causative Drugs
Most common culprits:
| Drug Class | Examples |
|---|---|
| Aromatic anticonvulsants | Phenytoin, phenobarbital, carbamazepine, lamotrigine |
| Anti-gout | Allopurinol |
| Sulfonamides | TMP-SMX |
| Antibiotics (other) | Minocycline, vancomycin, dapsone |
| Antiretrovirals | Nevirapine, abacavir |
| NSAIDs | - |
| ACE inhibitors | - |
| Calcium channel blockers | - |
| Antipsychotics | Clozapine, quetiapine |
| Anti-TB drugs | Rifampicin, isoniazid |
Higher-risk drugs (>3% of treated patients): aminopenicillins, allopurinol, sulfonamides, anticonvulsants.
- Tintinalli's EM, p. 1668; Dermatology 2-Volume Set 5e
Pathogenesis
DRESS is now understood as a multistep immune process:
- Reactive drug metabolites disturb the balance between cytotoxic and regulatory immune responses
- CD4+ and CD8+ T cells strongly expressing perforin and granzyme are recruited - cytotoxic activity kills keratinocytes
- Viral reactivation - particularly HHV-6 and HHV-7, but also CMV and EBV, is implicated in pathogenesis
- Drug-related immunosuppression (or induction of viral replication) leads to viral reactivation, which stimulates a cellular immune response
- HHV-6 transmits to skin-infiltrating CD4+ T cells, amplifying the reaction
- Drug-specific T cells have been isolated from blood and skin in lamotrigine- and carbamazepine-induced cases
- Dermatology 5e, blocks 5 and 18
Clinical Features
Skin
DRESS syndrome caused by phenytoin (Tintinalli's Emergency Medicine)
| Feature | Frequency |
|---|---|
| Maculopapular rash | 60-100% |
| Rash >50% BSA | 45-80% |
| Facial edema | 40-85% |
| Mucosal involvement (mouth/throat/lips) | 50% |
| Purpura | 10-30% |
| Pustules | 15-30% |
| Eye involvement | 10-15% |
The rash morphology is variable - ranges from morbilliform/maculopapular to exfoliative dermatitis or even bullous/SJS-like eruption.
Systemic Features
- Fever (high)
- Lymphadenopathy (at least 2 sites, nodes >1 cm)
- Liver - most commonly affected visceral organ; hepatitis/hepatocellular injury
- Kidney - interstitial nephritis
- Lung - pneumonitis
- Heart - myocarditis (rare but serious)
- Endocrine - thyroid dysfunction (may occur weeks to months after resolution)
- Neurologic, GI involvement also reported
Hematologic Abnormalities
| Finding | Frequency |
|---|---|
| Eosinophilia | 30-95% (notably absent in ~30%) |
| Atypical lymphocytes | 30-65% |
| Lymphocytosis / lymphopenia | variable |
| Thrombocytopenia | occasional |
- Dermatology 5e (frequency table); Rosen's EM, p. 1899
Diagnosis - RegiSCAR Scoring System
The European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) validated scoring system:
| Criterion | No | Yes | Unknown |
|---|---|---|---|
| Fever ≥38.5°C | -1 | 0 | -1 |
| Lymphadenopathy (≥2 sites; >1 cm) | 0 | +1 | 0 |
| Circulating atypical lymphocytes | 0 | +1 | 0 |
| Peripheral hypereosinophilia | (see subgroups) | +1 or +2 | 0 |
| Skin involvement (extent, morphology, biopsy suggesting DRESS) | variable | +1 or +2 | 0 |
| Organ involvement (liver, kidney, lung, muscle/heart) | 0 | +1 per organ, max +2 | 0 |
| Resolution >15 days | -1 | 0 | 0 |
| Exclusion of other causes (ANA, blood cultures, serology) | -1 | +1 | 0 |
Score interpretation:
- <2 = No DRESS
- 2-3 = Possible DRESS
- 4-5 = Probable DRESS
-
5 = Definite DRESS
- Dermatology 5e, RegiSCAR table, block 5
Key Warning Signs of a Severe Cutaneous Adverse Reaction (SCAR)
Cutaneous: Skin pain, confluent erythema, facial edema, blisters/epidermal detachment, mucosal erosions, necrosis, palpable purpura
Systemic: High fever, lymphadenopathy, arthralgia, dyspnea/wheezing, hypotension, visceral involvement
Labs: Marked eosinophilia, lymphocytosis with atypical lymphocytes, leukopenia, abnormal LFTs/renal function, thrombocytopenia
- Dermatology 5e, eTable 21.3
Differential Diagnosis
- Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (look for mucosal erosions, skin detachment)
- Drug-induced pseudolymphoma / angioimmunoblastic T-cell lymphoma
- Infectious mononucleosis (EBV)
- Viral exanthem
- Serum sickness-like reaction
Management
- Immediate discontinuation of the suspected culprit drug - single most important step
- Systemic corticosteroids in severe cases (hepatitis, pneumonitis, extensive exfoliative dermatitis) - prednisolone 1-2 mg/kg/day with slow taper
- Supportive care - antipyretics, antihistamines/antipruritic agents, fluid management, wound care
- Hospital admission in all confirmed/probable cases
- Monitor for relapse - DRESS can flare weeks after drug cessation, especially if steroids are tapered too quickly
- Monitor for late sequelae - autoimmune thyroid disease, type 1 diabetes, and other autoimmune diseases can emerge months after acute DRESS
- Family counseling - discuss genetic risk with relatives of the patient
- Tintinalli's EM, p. 1669; Rosen's EM, p. 1899
Prognosis
- Mortality: up to 10% (primarily from fulminant hepatitis or myocarditis)
- Resolution is typically slow (>15 days after drug cessation is characteristic)
- Long-term autoimmune complications (thyroiditis, type 1 DM) may develop months to years later
- The condition can be misdiagnosed early due to its variable presentation and the delayed onset after drug initiation
Recent Evidence
A 2025 EAACI position paper (PMID 40589376) published a systematic review specifically on DRESS diagnosis and management in children, confirming that the RegiSCAR criteria require pediatric adaptation. A 2023 review (PMID 37575981) highlights the expanding list of culprit drugs and the importance of HHV-6 serology in workup.
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