Drug hypersensitivity reactions

Last updated: August 14, 2023

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Summarytoggle arrow icon

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 DHR vs non-immediate DHR). 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.”

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Classificationtoggle arrow icon

Most DHRs are classified by either mechanism or clinical features; mixed DHRs are ones that do not fit into a single category. [2][3]

  • Mechanism: allergic DHR (i.e., drug allergy) or nonallergic DHR
  • Clinical features
    • Immediate DHRs
      • Mast-cell mediated (IgE-dependent or IgE-independent) [3]
      • 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

Clinical featurestoggle arrow icon

Immediate DHRs

Severity of immediate DHRs [7][8]
Severity Description
(grade 1)
  • Involvement of skin and subcutaneous tissues (e.g., generalized erythema, flushing, pruritus)
  • Involvement of a single organ or system (e.g., nausea, mild back pain)
(grade 2)
(grade 3)
  • Involvement of at least 2 organs or systems
  • Significant decrease in blood pressure (systolic BP < 90 mm Hg) and/or oxygen saturation (< 92%)

Nonimmediate DHRs

Immediate DHRs often resemble viral infections; nonimmediate DHRs commonly manifest as drug-induced skin reactions but can cause a variety of syndromes. [14]

Diagnosticstoggle arrow icon

Diagnosis can often be made on history and clinical findings but occasionally more advanced testing is required to confirm the diagnosis. [2]

Confirmatory testing [2][5]

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 [2][5][15]

  • 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.

Managementtoggle arrow icon

General principles [2][5][14]

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. [14]

Supportive care

Induction of drug tolerance (drug desensitization) [5]

See “Allergen 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

Preventiontoggle arrow icon

Prevention of subsequent episodes

Contrast allergy premedication [16]

DHR to contrast can be immediate (IgE-mediated or nonimmunologic) or nonimmediate (T-cell mediated). [16]

Subtypes and variantstoggle arrow icon

Severe cutaneous adverse reactions (SCAR)


A group of four type IV DHRs associated with significant morbidity and mortality: [18][19]

Red flags for SCARs [20]

Management [20]

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Referencestoggle arrow icon

  1. $Contributor Disclosures - Drug hypersensitivity reactions. None of the individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy:.
  2. Dispenza MC. Classification of hypersensitivity reactions. Allergy Asthma Proc. 2019; 40 (6): p.470-473.doi: 10.2500/aap.2019.40.4274 . | Open in Read by QxMD
  3. Demoly P, Adkinson NF, Brockow K, et al. International Consensus on drug allergy. Allergy. 2014; 69 (4): p.420-437.doi: 10.1111/all.12350 . | Open in Read by QxMD
  4. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis—a practice parameter update 2015. Annals of Allergy, Asthma & Immunology. 2015; 115 (5): p.341-384.doi: 10.1016/j.anai.2015.07.019 . | Open in Read by QxMD
  5. Solensky R, Khan DA et al. Drug Allergy: An Updated Practice Parameter. Ann Allergy Asthma Immunol. 2010; 105 (4): p.259-273.e78.doi: 10.1016/j.anai.2010.08.002 . | Open in Read by QxMD
  6. Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options.. Am Fam Physician. 2003; 68 (9): p.1781-90.
  7. Broyles AD, Banerji A, Castells M. Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: General Concepts. The Journal of Allergy and Clinical Immunology: In Practice. 2020; 8 (9): p.S3-S15.doi: 10.1016/j.jaip.2020.08.002 . | Open in Read by QxMD
  8. Brown SGA. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004; 114 (2): p.371-376.doi: 10.1016/j.jaci.2004.04.029 . | Open in Read by QxMD
  9. Shah N, Shah M, Drucker AM, Shear NH, Ziv M, Dodiuk-Gad RP. Granulomatous Cutaneous Drug Eruptions: A Systematic Review. Am J Clin Dermatol. 2020; 22 (1): p.39-53.doi: 10.1007/s40257-020-00566-4 . | Open in Read by QxMD
  10. Tesfa D, Keisu M, Palmblad J. Idiosyncratic drug-induced agranulocytosis: Possible mechanisms and management. Am J Hematol. 2009; 84 (7): p.428-434.doi: 10.1002/ajh.21433 . | Open in Read by QxMD
  11. Curtis BR. Non–chemotherapy drug–induced neutropenia: key points to manage the challenges. Hematology. 2017; 2017 (1): p.187-193.doi: 10.1182/asheducation-2017.1.187 . | Open in Read by QxMD
  12. Schwaiblmair M. Drug Induced Interstitial Lung Disease. Open Respir Med J. 2012; 6 (1): p.63-74.doi: 10.2174/1874306401206010063 . | Open in Read by QxMD
  13. Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020; 202 (3): p.e36-e69.doi: 10.1164/rccm.202005-2032st . | Open in Read by QxMD
  14. Ariza A, Mayorga C, Bogas G, et al. Advances and novel developments in drug hypersensitivity diagnosis. Allergy. 2020; 75 (12): p.3112-3123.doi: 10.1111/all.14603 . | Open in Read by QxMD
  15. Aberer W, Bircher A, Romano A, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003; 58 (9): p.854-863.doi: 10.1034/j.1398-9995.2003.00279.x . | Open in Read by QxMD
  16. Phillips EJ, Chung W-H, Mockenhaupt M, Roujeau J-C, Mallal SA. Drug hypersensitivity: Pharmacogenetics and clinical syndromes. J Allergy Clin Immunol. 2011; 127 (3): p.S60-S66.doi: 10.1016/j.jaci.2010.11.046 . | Open in Read by QxMD
  17. 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.
  18. Mustafa SS, Ostrov D, Yerly D. Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management. Curr Allergy Asthma Rep. 2018; 18 (4).doi: 10.1007/s11882-018-0778-6 . | Open in Read by QxMD
  19. Sánchez-Borges M, Aberer W, Brockow K, et al. Controversies in Drug Allergy: Radiographic Contrast Media. J Allergy Clin Immunol Pract. 2019; 7 (1): p.61-65.doi: 10.1016/j.jaip.2018.06.030 . | Open in Read by QxMD
  20. 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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