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Drug reactionEmergencyICD-10 T88.7

DRESS syndrome

Drug reaction with eosinophilia and systemic symptoms · drug-induced hypersensitivity syndrome (DIHS)

DRESS is a severe T-cell-mediated drug reaction characterised by extensive cutaneous eruption, fever, lymphadenopathy, haematological abnormalities (eosinophilia, atypical lymphocytes) and multi-organ involvement — most commonly hepatic, renal, cardiac, pulmonary and thyroid. Onset is typically 2-8 weeks after starting the culprit drug. Aetiology overlaps with SJS/TEN — anticonvulsants, allopurinol, sulfonamides, antiretrovirals — and now ICIs. HHV-6 / HHV-7 reactivation is implicated. Mortality is ~5-10%, with long-term autoimmune sequelae (thyroiditis, T1DM, AIHA, vitiligo) in ~10-20%.

CurrentLast reviewed 16 May 2026

Aetiology and pathogenesis

  • Onset 2-8 weeks after culprit drug exposure.
  • Highest-risk drugs:
    • Anticonvulsants: carbamazepine, phenytoin, lamotrigine, phenobarbital.
    • Allopurinol (HLA-B*58:01).
    • Sulfonamides — sulfasalazine, sulfamethoxazole.
    • Antiretrovirals — abacavir (HLA-B*57:01), nevirapine.
    • Minocycline, vancomycin, dapsone.
    • Immune-checkpoint inhibitors — rare but recognised.
  • HHV-6 / HHV-7 reactivation often occurs at 2-4 weeks → second eruption / hepatitis flare; also CMV, EBV.
  • HLA association in some drugs guides high-risk-population testing pre-prescription.

Clinical features (RegiSCAR criteria)

RegiSCAR inclusion criteria — ≥3 of (the validated RegiSCAR / Kardaun score then grades the case as no / possible / probable / definite DRESS):

  • Hospitalised inpatient.
  • Suspected drug-related.
  • Acute rash.
  • Fever >38°C.
  • Enlarged lymph nodes in ≥2 sites.
  • Internal organ involvement.
  • Lymphocyte / blood-count abnormalities (atypical lymphocytes, eosinophilia >700/µL or 10%, thrombocytopenia).

Skin:

  • Morbilliform / urticarial eruption affecting >50% BSA; later evolution to dusky / oedematous infiltrated plaques, vesicles, pustules.
  • Facial oedema — characteristic.
  • Centrifugal spread; mucosal involvement in ~50% but mild.

Systemic:

  • Hepatitis (most common organ involvement; can be severe).
  • Nephritis (interstitial), pneumonitis, myocarditis, pancreatitis, encephalitis.
  • Thyroid involvement — early hyperthyroidism may follow with delayed Hashimoto-type hypothyroidism.

Investigations

  • FBC + blood film: eosinophilia, atypical lymphocytes.
  • LFT, U&E, glucose, amylase; troponin, CK.
  • Coagulation; CRP, ferritin.
  • TFT (baseline + 6-12 months).
  • HHV-6, HHV-7, CMV, EBV PCR / serology at presentation and 2-4 weeks.
  • HIV, HBV / HCV serology.
  • Echocardiogram, ECG, CXR.
  • HLA typing in carbamazepine, allopurinol, abacavir cases.
  • Skin biopsy: perivascular lymphocytic infiltrate with eosinophils; non-specific.
  • RegiSCAR scoring.

Differentials

  • SJS / TEN — full-thickness epidermal necrolysis; mucosal predominant.
  • AGEP — sterile pustules within hours-days.
  • Acute viral exanthem (CMV, EBV, HHV-6).
  • Acute viral hepatitis.
  • Lymphoma, particularly angioimmunoblastic T-cell lymphoma.
  • HLH / macrophage activation syndrome.
  • Adult-onset Still disease.
  • HHV-6 / -7 reactivation alone.

Management

  • Withdraw all non-essential drugs; identify likely culprit; document drug allergy.
  • Admit all patients with multi-organ involvement.
  • Systemic corticosteroids: prednisolone 0.5-2 mg/kg/day with slow taper over 6-12 weeks; reduces inflammation but does not reliably prevent — and may promote — HHV-6 reactivation.
  • Severe / refractory: IVIG, ciclosporin, methotrexate, mycophenolate, rituximab in selected cases.
  • Topical: emollients, mid-potency steroids.
  • Antiviral (ganciclovir / valganciclovir) if confirmed CMV / HHV-6 reactivation with hepatitis or encephalitis.
  • Long-term follow-up:
    • Thyroid function every 3-6 months for 12 months.
    • Autoimmune surveillance — T1DM, Hashimoto, Graves, AIHA, vitiligo, lupus reported.
    • Drug allergy MedicAlert; counsel re cross-reactivity (anticonvulsants share risk).

References

  1. Kardaun SH et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Br J Dermatol. 2007;156:609-611.
  2. Cacoub P et al. The DRESS syndrome: a literature review. Am J Med. 2011;124:588-597.
  3. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DIHS) / drug reaction with eosinophilia and systemic symptoms (DRESS): an update. Allergol Int. 2019;68:301-308.
  4. British Association of Dermatologists. DRESS syndrome — patient information leaflet. London: BAD; 2022.

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