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Emergency: requires immediate attention
Drug-induced hypersensitivity syndrome in Adult
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Other Resources UpToDate PubMed
Emergency: requires immediate attention

Drug-induced hypersensitivity syndrome in Adult

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Contributors: Philip I. Song MD, Susan Burgin MD
Other Resources UpToDate PubMed

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Synopsis

Drug-induced hypersensitivity syndrome : Facial edema, Fever, Hepatomegaly, Rash, ALT elevated, AST elevated, Lymphadenopathy, Proteinuria, Widespread distribution, WBC elevated, EOS increased
Drug-induced hypersensitivity syndrome (DIHS), or drug reaction with eosinophilia and systemic symptoms (DRESS), is a serious multisystem drug reaction. It is an idiosyncratic reaction consisting of fever, rash, eosinophilia, and internal organ involvement. It tends to occur between 2-8 weeks after starting a new medication but may develop months later. A rash is present in over 80% of cases. Additional clinical findings include pharyngitis, lymphadenopathy, and facial and hand edema, while internal organ involvement most commonly affects the liver and hematologic and renal systems. Some cases may also be associated with reactivated viral infection (eg, human herpesviruses 6 and 7 or Epstein-Barr virus), although the pathogenic role of this viral reactivation, if any, is yet to be determined. A genetic predisposition has been identified; a number of HLA genes have been shown to be genetic markers for severe cutaneous adverse reactions, including DIHS.

The most commonly implicated drug groups causing DIHS include anticonvulsants, sulfonamides, and nonsteroidal anti-inflammatory drugs (NSAIDs). Anticonvulsants include phenytoin, carbamazepine, phenobarbital, and lamotrigine. (DIHS secondary to anticonvulsants is occasionally referred to as anticonvulsant hypersensitivity syndrome.) Sulfonamide-induced DIHS can have an earlier onset than hypersensitivity syndromes caused by other classes of antibiotics, appearing as early as 7-14 days after initiation of therapy. Minocycline, allopurinol, azathioprine, metronidazole, dapsone, antiretroviral agents (eg, abacavir), clopidogrel, and ticlopidine are other known causes of DIHS.

Any new drugs taken in the preceding 2 months before the onset of fever, rash, liver dysfunction, lymphadenopathy, and other signs of systemic illness should be considered suspect inducers of DIHS.

It is imperative to withdraw the suspect medication(s) as soon as possible, as there is a 10% mortality associated with this syndrome. Liver and cardiac involvement are the leading causes of death. Long-term sequelae of DIHS include autoimmune conditions such as thyroiditis, myocarditis, pancreatitis, or systemic lupus erythematosus, or infectious complications such as herpesvirus infections and pneumonia (typically seen in the corticosteroid dosing reduction phase).

Codes

ICD10CM:
L27.0 – Generalized skin eruption due to drugs and medicaments taken internally

SNOMEDCT:
427640001 – Non-allergic drug hypersensitivity disorder

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Best Tests

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Management Pearls

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Therapy

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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References

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Last Reviewed:01/30/2017
Last Updated:11/01/2022
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Emergency: requires immediate attention
Drug-induced hypersensitivity syndrome in Adult
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A medical illustration showing key findings of Drug-induced hypersensitivity syndrome : Facial edema, Fever, Hepatomegaly, Rash, ALT elevated, AST elevated, Lymphadenopathy, Proteinuria, Widespread distribution, WBC elevated, EOS increased
Clinical image of Drug-induced hypersensitivity syndrome - imageId=3727. Click to open in gallery. caption: 'Widespread erythema and secondary purpuric macules on the leg of a patient with hypersensitivity syndrome from an anticonvulsant.'
Widespread erythema and secondary purpuric macules on the leg of a patient with hypersensitivity syndrome from an anticonvulsant.

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