DRESS syndrome rash minocycline

Which of the following best describes the pictured rash occurring 4 weeks after starting minocycline?

  1. Anaphylaxis
  2. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome
  3. Erythema multiforme
  4. Serum sickness
  5. Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)

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.


  1. Hama N, Abe R, Gibson A, Phillips EJ. Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis. J Allergy Clin Immunol Pract. 2022;10(5):1155-1167.e5. PMID: 35176506
  2. Lewin JM, Lewin NA, Nelson LS. Dermatologic Principles. In: Nelson L, Howland MA, Lewin NA, Goldfrank LR, Hoffman RS, eds. Goldfrank’s Toxicologic Emergencies. Eleventh edition. McGraw Hill; 2019.
  3. Calle AM, Aguirre N, Ardila JC, Cardona Villa R. DRESS syndrome: A literature review and treatment algorithm. World Allergy Organ J. 2023;16(3):100673. PMID: 37082745
  4. Sasidharanpillai S, Ajithkumar K, Jishna P, et al. RegiSCAR DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Validation Scoring System and Japanese Consensus Group Criteria for Atypical Drug-Induced Hypersensitivity Syndrome (DiHS): A Comparative Analysis. Indian Dermatol Online J. 2022;13(1):40-45. PMID: 35198466
  5. Sim DW, Yu J, Koh YI. Efficacy of add-on therapy with intravenous immunoglobulin in steroid hyporesponsive DRESS syndrome. Clin Transl Sci. 2022;15(3):782-788. PMID: 34796665
  6. Jörg L, Helbling A, Yerly D, Pichler WJ. Drug-related relapses in drug reaction with eosinophilia and systemic symptoms (DRESS). Clin Transl Allergy. 2020;10(1):52. PMID: 33292540
Destiny D. Folk, MD

Destiny D. Folk, MD

Emergency Medicine Resident
Carolinas Medical Center
Destiny D. Folk, MD

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Kathryn T. Kopec, DO

Kathryn T. Kopec, DO

Associate Professor of Emergency Medicine
Medical Toxicologist
Carolinas Medical Center