What are the diagnosis and treatment options for Dress syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)?

Diagnosis and Treatment of DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)

Immediate discontinuation of the suspected causative drug is the most critical first step in managing DRESS syndrome, followed by prompt dermatology consultation and systemic corticosteroid therapy for all suspected cases. 1

Diagnosis

Clinical Features

• DRESS syndrome typically presents with fever, lymphadenopathy, hematologic abnormalities (especially eosinophilia), multisystem involvement, and skin rash 2
• Onset usually occurs after 6 weeks of treatment with the offending drug, which distinguishes it from other drug reactions 1
• Skin manifestations include diffuse erythematous macular rash, which may progress to more severe forms 3
• Internal organ involvement commonly affects the liver, kidneys, lungs, and heart 2

Diagnostic Workup

• Complete total body skin examination with attention to all mucous membranes 4
• Laboratory tests should include:
  • Complete blood count with differential (looking for eosinophilia and atypical lymphocytes) 1
  • Liver and kidney function tests 1
  • Urinalysis to assess for associated nephritis 4
  • Blood cultures if fever is present 4
• Skin biopsy to assess for histological changes consistent with DRESS and rule out other conditions 4, 1
• Follow patients closely using serial clinical photography to track skin manifestations 4, 1

Diagnostic Criteria

• The diagnosis of DRESS is based on clinical presentation and laboratory findings 1
• Patch testing may be useful for identifying the culprit drug, with sensitivity >50% for many drugs, but should be delayed until ≥6 months after the acute reaction and ≥1 month after discontinuation of systemic corticosteroids 4
• Delayed intradermal testing (dIDT) may be more sensitive than patch testing for certain drugs 4

Treatment

Immediate Management

• Discontinue the suspected causative drug immediately 1
• Consult dermatology for all suspected cases 1
• For severe cases, admit to a burn unit or ICU with dermatology and wound care services consultation 4, 1

Systemic Therapy

• For moderate to severe DRESS:

  • Initiate systemic corticosteroids: prednisone 0.5-1 mg/kg/day orally or methylprednisolone 1-2 mg/kg/day IV 4, 1
  • Taper corticosteroids slowly over at least 4 weeks to prevent relapse 4, 1
  • Prolonged immunosuppression may be necessary due to T-cell immune-directed toxicity 1

• For steroid-unresponsive cases:

  • Consider intravenous immunoglobulin (IVIG) at a total dosage of 1-2 g/kg 1, 5
  • IVIG may hasten recovery, with fever resolving within a median time of 1 day and liver enzymes improving substantially within a median time of 13 days 5
  • Cyclosporine is an effective alternative, particularly in patients who cannot tolerate prolonged immunosuppression 1, 6
  • Short courses of cyclosporine (mean treatment length of 5.26 days) have shown resolution of symptoms in 89% of patients 6

Supportive Care

• Provide supportive care including:
  • Fluid and electrolyte balance management 4, 1
  • Minimize insensible water losses 4
  • Prevent infection 4, 1
  • Topical treatment with emollients and petrolatum ointment 4
  • Oral antihistamines for symptom relief 4

Monitoring and Follow-up

• Monitor for progression to greater body surface area involvement and/or mucous membrane involvement 4
• Consult appropriate specialists based on organ involvement (ophthalmology, otolaryngology, urology, or gynecology for mucous membrane involvement) 1
• Monitor for viral reactivation (especially human herpes virus 6, Epstein-Barr virus, and cytomegalovirus), which is associated with poor outcomes 2, 7
• Be vigilant for potential long-term complications such as autoimmune disorders or sequelae due to organ failure 7

Prognosis and Complications

• DRESS syndrome carries significant mortality risk, with death occurring in severe cases despite appropriate treatment 3
• A subset of patients may have a prolonged course with recurrence (reported in 16% of cases treated with cyclosporine) 6, 7
• Long-term complications include autoimmune disorders and organ damage 7
• Viral reactivation is common and associated with poor outcomes 2

Special Considerations

• Unlike in Stevens-Johnson syndrome, corticosteroids are not contraindicated in DRESS syndrome 1
• Prophylactic use of corticosteroids when initiating medications known to cause DRESS is not recommended as it may increase the risk of skin rash 1
• Patients with a history of DRESS should permanently avoid the culprit drug and potentially cross-reactive medications 4