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Drug Allergy: Overview, Diagnosis, and Treatment

About Drug Allergy

Adverse drug reactions (ADRs) or drug hypersensitivity reactions (DHRs) can be divided into nonimmunologic reactions and immunologic reactions.1 ADRs are common, affecting between 15 percent to 25 percent of patients, with serious reactions occurring in 7 percent to 13 percent of patients.2 It is estimated that adverse effects of drugs are the cause of about 5 percent of hospital admissions and occur in 10 percent to 20 percent of hospitalized patients.1

ADRs are classified as either unpredictable reactions that may occur in anyone or predictable reactions that occur only in susceptible individuals.2 Drug allergy is a type of unpredictable IgE-mediated ADR to a pharmaceutical and/or formulation in a sensitized person.2,3 An allergy to medications can affect patient quality of life, and may also lead to delayed treatment, use of suboptimal alternate medications, and even death.2

The most common manifestation of drug allergy is generalized exanthema (also known as a maculopapular rash), which is characterized by raised, spotted lesions that can appear within days or up to three weeks after drug exposure.2 It is estimated that this rash comprises about 75 percent of all allergic reactions caused by drugs.1

Skin reactions are the most common physical manifestation of drug-induced allergic reactions, but it can also manifest as organ or systemic reactions.1 Examples of systemic allergic reactions are anaphylaxis, serum sickness, various types of rash with eosinophilia and systemic symptoms (i.e., drug rash with eosinophilia and systemic symptoms, aka DRESS).1 Although skin manifestations are the most common, many other organ systems may be involved, including the renal, hepatic, and hemolytic systems.Multi-organ reactions may also occur, and include anaphylaxis.2

Serum sickness is an immune-complex-mediated reaction that presents with fever, lymphadenopathy, arthralgia, and cutaneous lesions. Classic serum sickness is caused by heterologous proteins, such as rabbit antithymocyte globulin or equine-derived anti-toxins, and is more common in adults. Serum sickness-like reactions are more common in children and tend to occur after infections or administration of some vaccines or drugs such as cefaclor and penicillin. However, serum sickness-like reactions may also occur with newer mAbs that contain foreign murine components in the variable regions. The exact mechanism of serum sickness-like reactions is poorly understood.5

 

15% to 25% of patients

Adverse drug reactions are common, affecting between 15 percent to 25 percent of patients.2

Adverse drug reactions have varying clinical presentations, but typically involve:4

  • Urticaria
  • Angioedema
  • Rhinitis
  • Conjunctivitis
  • Bronchospasm
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea)
  • Anaphylaxis, which can lead to cardiovascular collapse (anaphylactic shock) 

Skin reactions are the most common physical manifestation of drug-induced allergic reactions, but it can also manifest as organ or systemic reactions.1

Drug allergy: Refining differential diagnosis through testing

Diagnosis of drug allergy is quite complicated given myriad symptoms and clinical presentations associated with the condition, and usually begins with an extensive medical history.1,2

Evaluation of the patient with a suspected drug allergy should include a detailed history of all drugs taken by the patient, including:2

  • Dates of administration
  • Formulation, dosage, and route of administration
  • Symptom timing and duration in relation to drug exposure
  • Previous drug exposures and reactions

The diagnosis of drug allergy is based on a detailed history of the onset of symptoms and signs that are compatible with drug-induced allergic reactions.2

To facilitate the recording of an appropriate history, a questionnaire has been developed that might provide a guide in this rather difficult area of clinical medicine.6

Depending on the history and physical examination results, carefully selected diagnostic tests including specific IgE tests may be required.2
 

Who should be tested?

Healthcare providers should evaluate for drug allergy when there is a history of prior ADRs and the drug is required without an equally effective, structurally unrelated alternative, and if the risk/possible benefit ratio is positive or when there is a history of severe ADRs for other drugs.4

Drug hypersensitivity reactions are most common in patients over 50 years of age and up to 70 percent of patients suspected of having an allergic reaction to drugs are women.1

Not sure which allergy or autoimmune disease could be behind your patient’s symptoms? Use this interactive tool to take the next step in making your differential diagnosis. 

Common drug allergies

Penicillin is the most frequent drug allergy, affecting approximately 10 percent of patients.Five percent of the population have allergic reactions to penicillin and other β-lactam antibiotics.1

 

Other common allergens include:2

  • Sulfonamide antibiotics
  • Radiocontrast media (RCM)
  • Local and general anesthetics
  • Acetylsalicylic acid (ASA) drugs
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 

 

Testing Confidence

Testing Increases Diagnostic Confidence

Adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis to 90 percent.i,ii Conventionally, a diagnosis of allergic or autoimmune disease relies on the case history and a physical examination. However, adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis.i,ii Diagnostic testing can also help to improve the patient’s quality of life and productivity, reduce costs associated with absenteeism, and optimize use of medication, in addition to decreasing unscheduled healthcare visits.iii,iv 

i. Duran-Tauleria E, Vignati G, Guedan MJ, et al. The utility of specific immunoglobulin E measurements in primary care. Allergy. 2004;59 (Suppl78):35-41.
ii. NiggemannB, Nilsson M, Friedrichs F. Paediatric allergy diagnosis in primary care is improved by in vitro allergen specific IgE testing. Pediatr Allergy Immunol. 2008;19:325-331
iii. Welsh N, et al. The Benefits of Specific Immunoglobulin E Testing in the Primary Care Setting. J Am Pharm Assoc. 2006;46:627.
iv. Szeinbach SL, Williams B, Muntendam P, et al. Identification of allergic disease among users of antihistamines. J Manag Care Pharm. 2004; 10 (3): 234-238

Learn about allergies.

Learn more about testing.

Management and care of patients with drug allergies

The most effective strategy for the management of drug allergy are:1,2,4

  • Discontinuation of the suspected drug.
  • Lifelong avoidance of the drug and cross-reactive drugs.

When available, alternative medications with unrelated chemical structures should be substituted.2

Prevention of future adverse drug reactions is an essential part of patient management. Healthcare providers often provide the patient with written information about which drugs to avoid, including any over-the-counter (OTC) medications.2 Engraved allergy medical bracelets and necklaces may also be considered, particularly if the patient has a history of severe reactions.2

Practice parameters have been developed to help guide the management and treatment of patients with drug allergies.

Practice Parameters

Practice parameters and guidelines

for drug allergy:

References

 

  1. Żukiewicz-Sobczak WA, Wróblewska P, Adamczuk P, Zwoliński J, Oniszczuk A, Wojtyła-Buciora P, Silny W. Drugs as important factors causing allergies. Postepy Dermatol Alergol. 2015 Oct;32(5):388-92. 
  2. Warrington R, Silviu-Dan F. Drug allergy. Allergy Asthma Clin Immunol. 2011 Nov 10;7(Suppl 1):S10. 
  3. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010; 105: 259–273. 
  4. Demoly P, Adkinson NF, Brockow K, et al. International consensus on drug allergy. Allergy.  2014;69(4):420–37.
  5. Warrington R, Silviu-Dan F, Wong, T. Drug allergy. Practical guide for allergy and immunology in Canada 2018. Allergy, Asthma, and Clinical Immunology. 2018 14(Suppl 2):60.
  6. Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity. Allergy. 1999; 54: 999-1003.