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Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening adverse drug reaction caused by delayed hypersensitivity to medication (most commonly anticonvulsants or antimicrobials). Risk factors include immunosuppression, human herpesvirus-6 (HHV-6) infection, and pharmacogenetic susceptibility. DRESS is characterized by delayed onset (2–8 weeks after drug exposure), waxing and waning symptoms, and a prolonged course. Symptoms typically include fever, diffuse rash, facial edema, lymphadenopathy, and internal organ involvement. Peripheral blood eosinophilia is common but not universally observed. Diagnosis is based on medication history, physical exam, blood tests, and skin biopsy. Management typically involves prompt withdrawal of all possible triggering agents, supportive care, and guidance from specialists for any affected organ. Patients should be carefully monitored for internal organ involvement and complications. The liver is the most commonly affected organ, usually with asymptomatic hepatic inflammation; necrosis and liver failure are also possible and the leading cause of death from DRESS.
- Common triggers 
- Risk factors 
Clinical manifestations in DRESS have a delayed onset (typically 2–8 weeks) after exposure to the offending agent. In rare cases in which a patient who has recovered from DRESS is reexposed to the triggering agent, the symptom onset is much faster (hours or days). 
- Systemic symptoms 
- Diffuse rash
- Facial edema 
Signs of internal organ involvement
- Liver (most common): can be asymptomatic or manifest as hepatomegaly or alterations in liver chemistries
- Renal: decreased GFR, proteinuria,
- Cardiac and muscle: pain, and/or weakness , muscle
- Pancreas: can be asymptomatic elevation in amylase and/or lipase, or
- Multiorgan failure in severe cases
Symptoms in DRESS usually manifest 2–8 weeks after drug exposure and often have a protracted clinical course with waxing and waning of symptoms even after the triggering agent is withdrawn. 
- Consider DRESS in patients with suggestive clinical features (e.g., fever, diffuse rash).
- Obtain a detailed history, with emphasis on the following:
- Medications and supplements started within the last 2–8 weeks
- Family history of drug-induced
- Obtain laboratory studies and a skin biopsy.
- Assess for internal organ involvement.
- Confirm diagnosis using a validated score (e.g., RegiSCAR).
- Routine laboratory studies
- Exclude alternative diagnoses
- Screen for viral reactivation: baseline serology and PCR for HHV–6, HHV–7, CMV, EBV 
Skin biopsy 
Biopsy findings in DRESS are typically nonspecific and therefore not required for diagnosis.
- Consider in all patients with suspected DRESS 
- Findings can include:
Biopsy is not required for diagnosis; findings in DRESS are typically nonspecific, so the procedure is most helpful for ruling out other etiologies of rash.
Evaluation for internal organ involvement 
The majority of patients (∼ 90%) have involvement of at least one organ/system, most commonly hepatic inflammation. Evaluate all patients for liver and kidney injury and consider other tests depending on the presence of clinical or laboratory features suggestive of involvement of other organs.
- Liver injury 
- Acute kidney injury (AKI)
- Myocarditis: Suspect in patients with hypotension, tachycardia, chest pain, dyspnea, or palpitations.
- Lung injury: Suspect in patients with cough and/or dyspnea.
- Skeletal muscle injury: Suspect in patients with pain or weakness.
- Involvement of the GI tract, pancreas, spleen, CNS, and thyroid gland is also possible.
Diagnostic criteria 
|RegiSCAR scoring system for diagnosing DRESS syndrome |
|Add 1 point for each||Reduce 1 point for each|
(max of 3 points)
| || |
(max of 5 points)
|Exclusion of other potential causes|| || |
- Stop all suspected offending agents immediately (i.e., drug withdrawal).
- Determine severity based on internal organ involvement 
- Start corticosteroids (topical or systemic based on severity).
- Provide supportive care as needed.
- Post-acute recovery: Consider referral to an allergist and monitoring for autoimmune sequelae. 
Withdrawal of all suspected triggering medications is the cornerstone of management for patients with suspected DRESS. Delays in medication withdrawal are associated with a prolonged course and worse prognosis. 
Nonserious DRESS 
- Admit all patients with nonserious DRESS to acute care. 
- Start therapy with topical corticosteroids (high or very high potency, e.g., clobetasol ). 
- Monitor for progression to serious DRESS and escalate therapy if needed.
Serious DRESS 
- Admit all patients with serious DRESS.
- Severe organ involvement: Consider ICU admission.
- Severe cutaneous involvement : Consider admission to a burn unit.
- Requires multidisciplinary management; consult specialists for affected organs.
- Perform clinical and laboratory monitoring for new or worsening organ involvement at least every 24 hours.
- Start pharmacological treatment in consultation with a specialist.
- First line: systemic corticosteroids (e.g., prednisone ) with a prolonged taper 
- Refractory cases or contraindications to corticosteroids: Consider cyclosporine, cyclophosphamide, plasmapheresis, or IVIG. 
- In the case of severe complications of viral reactivation (e.g., HSV encephalitis, CMV colitis): Consider ganciclovir or valganciclovir.
- DRESS is fatal in ∼10% of cases.