ACMT Toxicology Visual Pearl: Making Rash Decisions

2. DRESS Syndrome

What is DRESS syndrome?

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, also called Drug Induced Hypersensitivity Syndrome (DIHS), is a severe delayed T-cell mediated adverse drug reaction with a broad spectrum of clinical manifestations [1].
• Incidence: 1 in 5-10,000 exposures depending on the culprit drug [2]

What causes DRESS syndrome? [2]

• Multiple drugs have been reported to be the causative agent of DRESS syndrome. Frequently cited culprits include:
  • Anti-convulsants (phenytoin, carbamazepine, and phenobarbital)
  • Sulfonamides; sulfones (dapsone)
  • Nonsteroidal anti-inflammatory drugs (piroxicam, ibuprofen, and diclofenac)
  • Beta-lactam antibiotics, vancomycin, minocycline, and antiretrovirals
  • Allopurinol
• In 10-20% of cases, the causative drug is not identified.
• The syndrome typically presents 2-6 weeks after the drug is initiated.

How do patients with DRESS syndrome present? [1-3]

• Cutaneous manifestations typically consist of an urticarial, maculopapular eruption.
• Vesicles, bullae, pustules, purpura, facial edema, and/or erythroderma may be present.
• Other common features include:
  • Fever
  • Lymphadenopathy
  • Eosinophilia, leukocytosis, and thrombocytopenia
  • Elevated transaminases
• 50% of patients will develop one or more of the following
  • Hepatitis
  • Nephritis
  • Vasculitis
  • CNS effects
  • Pneumonitis
  • ARDS
  • Autoimmune hypothyroidism
• Fulminant hepatitis can occur and may lead to severe morbidity and mortality.

How do you diagnose DRESS syndrome? [3,4]

• Diagnosis is based on history of culprit drug use, physical exam findings, and laboratory testing.
• The RegiSCAR (Registry of Severe Cutaneous Adverse Reactions) group suggested the following criteria for diagnosing DRESS syndrome and a point scoring system determining negative, possible, probable, or definitive DRESS syndrome [MDCalc]:
  • Fever >38.5⸰C
  • Enlarged lymph nodes over 2 sites, over 1 cm
  • Eosinophilia
  • Atypical or reactive lymphocytes
  • Extensive rash over 50% total body surface area
  • Rash with at least 2 of: edema, infiltration, purpura, scaling
  • Biopsy suggestive of DRESS
  • Internal organ involvement
  • Resolution in >15 days
  • Evaluations of other causes negative

How do you treat patients with DRESS Syndrome? [2,3]

• Stop the culprit drug.
• Symptomatic treatment including antipyretics, antihistamines, topical steroids, and emollients should be utilized.
• Avoid NSAIDs.
• Antibiotics are only recommended, if infection is suspected.
• Severe DRESS syndrome is defined by evidence of moderate to severe organ involvement and should be treated with prednisolone 0.8-1 mg/kg/day for 2-3 weeks with gradual tapering over 4-6 weeks.
• If there is a lack of improvement/control or contraindication to corticosteroids, other treatment options such as cyclosporine, IVIG, and plasmapheresis have been used to successfully treat patients with DRESS syndrome [5].

What are the delayed effects of DRESS syndrome?

• Patients with DRESS syndrome are at risk of developing systemic autoimmune sequelae, which can appear anywhere from months to 4 years after the initial event [1].
• The most common autoimmune sequelae include [1]:
  • Autoimmune thyroiditis
  • Diabetes mellitus
  • Autoimmune hemolytic anemia
  • Alopecia
• Patients with DRESS syndrome are at increased risk of suffering from relapses which may occur with the original drug or with a new drug [6].

Clinical Pearls

• DRESS syndrome classically presents 2-6 weeks after starting a new drug — most commonly an anti-epileptic, antibiotic, NSAID, antiretroviral, or allopurinol.
• Common features include rash, fever, eosinophilia, transaminitis, and lymphadenopathy.
• Visceral involvement, most commonly hepatitis, can lead to morbidity and mortality.
• Treatment includes cessation of the culprit drug and consideration of systemic corticosteroids.