Drug reaction with eosinophilia and systemic symptoms

Overview

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but potentially life-threatening drug-induced hypersensitivity reaction. It is characterized by a combination of skin rash, fever, eosinophilia (high levels of a type of white blood cell), and involvement of internal organs such as the liver, kidneys, lungs, and heart. DRESS typically develops 2 to 8 weeks after the initiation of the offending medication, and symptoms can persist even after the drug is discontinued. Early recognition and management are critical to reducing morbidity and mortality.

Causes

DRESS syndrome is triggered by a hypersensitivity reaction to certain medications. It is not dose-dependent and is believed to involve a combination of genetic predisposition, immune dysregulation, and sometimes viral reactivation (especially human herpesvirus 6). Common drugs associated with DRESS include:

• Anticonvulsants: Such as phenytoin, carbamazepine, lamotrigine, and phenobarbital.

• Allopurinol: Used for treating gout; a frequent cause, especially in patients with renal impairment.

• Sulfonamides and other antibiotics: Including sulfasalazine, minocycline, and vancomycin.

• Antiretrovirals and immunomodulatory agents: Occasionally implicated.

Genetic factors, such as HLA allele variants, may increase susceptibility, particularly in certain ethnic groups.

Symptoms

The clinical presentation of DRESS syndrome is broad, but key features typically include:

• Fever: Often >38.5°C (101.3°F), usually the first symptom.

• Skin eruption: Widespread, red, itchy rash that may progress to exfoliative dermatitis.

• Facial edema: Swelling of the face, particularly around the eyes, is characteristic.

• Eosinophilia: Elevated eosinophil count in the blood.

• Lymphadenopathy: Swollen lymph nodes.

• Organ involvement:

  • Liver: Hepatitis with elevated liver enzymes is common.

  • Kidneys: Interstitial nephritis may occur.

  • Lungs: Pneumonitis can lead to respiratory symptoms.

  • Heart: Myocarditis or pericarditis in severe cases.

Symptoms can persist or worsen even after stopping the offending drug, making monitoring and early intervention critical.

Diagnosis

DRESS syndrome is diagnosed based on clinical criteria and the exclusion of other conditions. Key diagnostic components include:

• History: Recent use (within 2–8 weeks) of a high-risk medication.

• Blood tests:

  • Elevated eosinophil count.

  • Abnormal liver or kidney function tests.

  • Elevated inflammatory markers (e.g., ESR, CRP).

• Skin biopsy: May show features consistent with drug hypersensitivity but is not diagnostic on its own.

• Viral testing: HHV-6 or EBV reactivation may be observed.

• Diagnostic scoring systems: The RegiSCAR scoring system is often used to classify the likelihood of DRESS syndrome.

Treatment

Treatment of DRESS syndrome must begin with immediate withdrawal of the offending drug. Additional management includes:

• Systemic corticosteroids: First-line treatment, especially in cases with internal organ involvement (e.g., prednisone 1 mg/kg/day).

• Topical corticosteroids: May be used for milder skin symptoms.

• Supportive care: Including hydration, nutritional support, and monitoring of organ function.

• Antivirals: In cases of confirmed viral reactivation, though their use remains controversial.

• Immunosuppressive agents: In steroid-refractory cases, agents like cyclosporine or IVIG may be considered.

Patients require close monitoring during treatment, as symptoms can relapse or worsen with steroid tapering.

Prognosis

The prognosis of DRESS syndrome depends on the severity and timeliness of treatment. With early drug withdrawal and appropriate therapy, most patients recover, although the process can be prolonged. The condition has a mortality rate of around 10%, often due to severe organ failure (especially liver or heart). Some individuals may experience long-term complications such as thyroiditis, diabetes, or chronic organ dysfunction. Regular follow-up is essential to detect late-onset complications and manage relapses.