Drug hypersensitivity reactions

Last updated: October 26, 2022

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Drug hypersensitivity reactions (DHR) are a group of adverse drug effects that resemble an allergy. They are relatively common, and may be classified by underlying pathophysiology (allergic DHR vs nonallergic DHR), or by onset of symptoms (immediate vs non-immediate). Clinical features can vary widely. Diagnosis is typically clinical but there are several methods available for confirmatory testing. Management depends on the underlying mechanism and clinical syndrome suspected, but all patients should stop the suspected offending drug and be provided with supportive care. Severe cutaneous adverse reactions (SCAR) refers to a group of four type IV DHRs that are associated with significant morbidity and mortality, including DRESS, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), all of which require prompt evaluation and management.

See also “Hypersensitivity reactions.”

Epidemiological data refers to the US, unless otherwise specified.

Most DHRs are classified by either mechanism or clinical features; mixed DHRs are ones that do not fit into a single category. [1][2]

  • Mechanism: allergic DHR (i.e., drug allergy) or nonallergic DHR
  • Clinical features
    • Immediate DHRs
      • Mast-cell mediated (IgE-dependent or IgE-independent) [2]
      • Onset typically within 1 hour of exposure
    • Nonimmediate DHRs
      • Typically T-cell mediated; can also be non-immune mediated
      • Onset typically > 1 hour after exposure

Immediate DHRs

  • Onset typically occurs within 1 hour of exposure.
  • Severe forms manifest as anaphylaxis and anaphylactoid reactions.
  • Clinical features can mimic those of viral infections.
  • Fever is typically absent.
Characteristic features of immediate DHRs [1][3][4]
System Clinical features Commonly associated medications [5]
Skin/mucosal
Respiratory
Gastrointestinal
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal cramping
Cardiovascular

Nonimmediate DHRs

Immediate DHRs often resemble viral infections; nonimmediate DHRs commonly manifest as drug-induced skin reactions but can cause a variety of syndromes. [11]

Diagnosis can often be made on history and clinical findings but occasionally more advanced testing is required to confirm the diagnosis. [1]

Confirmatory testing [1][3]

When indicated, confirmatory testing should be performed 4–6 weeks after the resolution of a suspected drug reaction to reduce the likelihood of false positive or false negative results.

Graded challenge test [1][3][12]

  • Description
    • The patient is exposed to increasing amounts of the drug until a full dose has been administered or an HSR occurs.
    • If the drug is tolerated, the patient does not have a DHR.
    • Does not distinguish between allergic and nonallergic reactions
  • Indications
    • To rule out DHR in individuals with an inconsistent clinical history or inconclusive evaluation
    • To assess safety in a patient who requires a drug that is related to a known or suspected DHR
  • Contraindications
    • Absolute: life-threatening or severe reactions
    • Relative

A graded challenge test does not induce drug tolerance and should only be used to demonstrate that a drug is safe for use in patients with a low likelihood of a true drug HSR.

A graded challenge test should only be performed by trained staff with access to resuscitative equipment.

General principles [1][3][11]

Management of DHRs varies depending on the underlying etiology and resulting syndrome.

Incorrectly labeling a patient as having drug allergies can lead to avoidance of essential medications, use of less effective or overly broad alternative medications (e.g., antibiotics), and unnecessary desensitization procedures. [11]

Supportive care

Induction of drug tolerance (drug desensitization) [3]

See “Allergy immunotherapy” for more detailed information.

  • Goal: to enable safe administration of a drug through modification of the patient's immune response
  • Indication: offending drug is essential and no satisfactory alternatives exist
  • Contraindications: history of severe non-IgE-mediated reaction; history of ACEI angioedema
  • Method: administration of incrementally increasing doses of the offending drug
  • Outcome: temporary drug tolerance

Prevention of subsequent episodes

Contrast allergy premedication [13]

DHR to contrast can be immediate (IgE-mediated or nonimmunologic) or nonimmediate (T-cell mediated). [13]

Severe cutaneous adverse reactions (SCAR)

Definition

A group of four type IV DHRs associated with significant morbidity and mortality: [15][16]

Red flags for SCARs [17]

Management [17]

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  14. Choudhary S, McLeod M, Torchia D, Romanelli P. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. J Clin Aesthet Dermatol. 2013; 6 (6): p.31-7.
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  17. Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol. 1991; 87 (4): p.867-872. doi: 10.1016/0091-6749(91)90135-b . | Open in Read by QxMD

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