Drug Reaction with Eosinophilia and Systemic Symptoms

Drug reaction with eosinophilia and systemic symptoms (DRESS), also called drug induced hypersensitivity syndrome, is a delayed, multiorgan T-cell mediated drug reaction with rash, fever, eosinophilia, lymphadenopathy, and visceral involvement.

• Incidence is about 1 in 1,000 to 10,000 drug exposures. Onset is 2 to 8 weeks after starting the drug, and mortality is about 5 to 10%.
• Drugs: allopurinol (HLA-B*58:01), carbamazepine (HLA-B*15:02, A*31:01), phenytoin, phenobarbital, lamotrigine, sulfasalazine, dapsone, vancomycin, minocycline, abacavir, nevirapine, and anti-TB drugs.
• Reactivation of human herpesvirus 6 (HHV-6), HHV-7, EBV and CMV drives relapse.
• Late autoimmune sequelae (thyroiditis, type 1 diabetes, lupus) can occur.

• Fever above 38 degrees Celsius, widespread morbilliform or exfoliative rash covering over 50% BSA, facial oedema (hallmark), lymphadenopathy.
• Organ involvement: liver (commonest, hepatitis), kidney (interstitial nephritis), lung (pneumonitis), heart (myocarditis), thyroid, and pancreas.
• Course is protracted, with flares after drug withdrawal over weeks to months.

• RegiSCAR scoring: fever, lymphadenopathy, eosinophilia (over 0.7 x 10^9/L or over 10%), atypical lymphocytes, rash features, biopsy, and organ involvement (at least one); definite score is 6 or above.
• Blood: full blood count with differential, liver tests (ALT often over 2x ULN), creatinine, urinalysis, CK, troponin, lipase, and TSH.
• Viral PCR for HHV-6, CMV, EBV. ECG and echocardiography if cardiac suspicion.
• Skin biopsy is non-specific (spongiosis, perivascular infiltrate).
• Exclude viral infection, Kawasaki disease, lymphoma, hypereosinophilic syndrome, SJS/TEN, and vasculitis.

• Immediately withdraw the offending drug (and cross reacting agents, e.g. aromatic anticonvulsants).
• Mild (skin only, minor transaminase rise): topical clobetasol 0.05% daily and emollients.
• Moderate to severe organ involvement: prednisolone 0.5 to 1 mg/kg/day, with slow taper over 6 to 12 weeks to prevent relapse; methylprednisolone 1 g IV daily for 3 days in life threatening organ failure.
• Steroid sparing or refractory: IVIG 2 g/kg, ciclosporin 3 to 5 mg/kg/day, mycophenolate, rituximab, plasmapheresis. Ganciclovir 5 mg/kg every 12 hours or valganciclovir when CMV reactivation with severe organ disease.
• Supportive care: fluids, antipyretics, nutrition, treat infection, ICU for organ failure.
• Long term follow up for thyroid function, glucose, autoantibodies for 1 to 2 years, and permanent allergy documentation. Test HLA in first degree relatives before prescribing implicated agents when risk is high.