Drug allergy medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2]

Drug Allergy

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Overview

The management strategies for drug allergy include both acute and long-term treatment, as well as drug desensitization and graded challenges for patients in whom the drug they are allergic to is absolutely neccesary for treatment.

General Management Strategies

  • Discontinuation of the allergen - The most effective strategy for treating or managing any type of allergy, is the immediate avoidance and discontinuation of the offending agent. When choosing drug therapy, alternative medications with unrelated chemical structures should be substituted for the chosen medication that has been known to cause allergy. Cross-reactivity of certain medications needs to be taken into account when selecting a treatment option. [1]
  • Supportive/ symptomatic therapy - topical steroids and antihistamines are useful for cutaneous symptoms.
  • Epinephrine - the treatment of choice in anaphylaxis is epinephrine, administered through intramuscular injection in the thigh.
  • Corticosteroids - corticosteroids may be used systemically in severe reactions, but in the case of anaphylaxis it should be noted that epinephrine must be given, and it must be given before corticosteroids.
  • Intensive care unit or burn unit - severe drug reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis are best treated in an intensive care unit or a burn unit setting, due to the special management required for such great amounts of insensible water loss from skin damage. [2]

Drug Desensitization and Graded Challenge

There are cases where there is a definite clinical need for a particular drug, but the diagnosis of drug allergy remains unclear despite thorough investigation. In these cases, a procedure can be done to induce drug tolerance by the patient. The two procedures used are called drug desensitization, or a graded challenge (also known as provocation testing). Drug desensitization can modify the patients immunologic or non-immunologic response to the drug, by gradually increasing the dose of the drug in small increments. Most procedures start with a very dilute form of the drug, and then double the dose of the drug every 20 minutes, until a full therapeutic dose of the drug is administered at 3-8 hours. The tolerance is usually maintained for the amount of time that the drug is administered, and the procedure needs to be repeated if the patient requires the drug again in the future. Graded challenge tests do not modify a patients immunologic or non-immunologic response to a given drug. These tests are generally used to determine whether a patient will have an adverse reaction to a particular drug by administration of sub-therapeutic doses over a period of time, while observing the patient for potential reactions. Both of these procedures are potentially harmful, and should only be performed by experienced personnel in facilities with resuscitative equipment readily available. [2]

Management Strategies for Specific Drugs

  • Penicillin - Treatment in penicillin allergic patients is best limited to non-penicillin agents. Carbapenems do not show a significant amount of cross-reactivity with penicillin, and may be administered as a graded challenge, after prophylactic skin testing with the chosen carbapenem. [3] Second or third generation cephalosporins may also be considered, as well as monobactams (unless the patient has had a prior reaction with ceftazidime). [4] Penicillin is the most common drug allergy, affecting up to 10 percent of patients. Ideal management of the patient with penicillin allergy should include penicillin skin testing, as up to 90% of patients will have negative skin test and will be able to recieve cephalosporins and other beta-lactam antibiotics safely. If penicillin is absolutely neccesary for treatment, desensitization should be considered and performed under medical supervision in a hospital. [2]
  • Sulfonamides - Patients infected with HIV are at an increased risk of developing cutaneous reactions to sulfonamide antbiotics, however trimethoprim-sulfamethoxazole (TMP-SMX) remains to be the treatment of choice for many HIV associated infections. Induction of drug tolerance procedures can be used to safely administer sulfonamide drugs.
  • Cephalosporins - Positive skin test to penicillin is associated with a higher likelihood of allergic reactions to first-generation cephalosporins. There is a role for skin testing with the chosen antibiotic for therapy, or for administering the drug by a graded challenge. Induction of drug tolerance procedures may be attempted if there is no alternative for the drug.
  • Radiocontrast media - radiocontrast dyes are known to cause both allergic and pseudo-allergic reactions, both of which can be life-threatening. There is a lower rate of reactions when using non-ionic agents, then when using ionic agents. Both types of reactions can be prevented by using pre-treatment regimens that include oral corticosteroids and H1 antihistamines. Low osmolarity agents should also be used if drug allergy is a concern. [5]
  • Local anesthetics - most reactions to local anesthetics are not actually due to the anesthetic itself, but due to preservatives in the medication or epinephrine. If the allergy is suspected to be a true IgE mediated drug allergy, skin test followed by graded challenge tests using epinephrine-free, preservative-free local anesthetics may be utilized. [2]
  • General anesthesia - rarely, anaphylaxis can occur to patients who are under general anesthesia. The investigation into such a reaction is particularly challenging as the patient is usually exposed to a myriad of drugs while under general anesthesia. Reactions are most likely due to neuromuscular blocking agents, as well as intravenous anesthetics, antibiotics, NSAIDS, and latex. Management includes identifying and avoiding the causative agents, and finding alternative agents to use in the future.

References

  1. Khan DA, Solensky R (2010). "Drug allergy". J Allergy Clin Immunol. 125 (2 Suppl 2): S126–37. doi:10.1016/j.jaci.2009.10.028. PMID 20176256.
  2. 2.0 2.1 2.2 2.3 Warrington R, Silviu-Dan F (2011). "Drug allergy". Allergy Asthma Clin Immunol. 7 Suppl 1: S10. doi:10.1186/1710-1492-7-S1-S10. PMC 3245433. PMID 22165859.
  3. Frumin J, Gallagher JC (2009). "Allergic cross-sensitivity between penicillin, carbapenem, and monobactam antibiotics: what are the chances?". Ann Pharmacother. 43 (2): 304–15. doi:10.1345/aph.1L486. PMID 19193579.
  4. Saxon A, Hassner A, Swabb EA, Wheeler B, Adkinson NF (1984). "Lack of cross-reactivity between aztreonam , a monobactam antibiotic, and penicillin in penicillin-allergic subjects". J Infect Dis. 149 (1): 16–22. PMID 6537963.
  5. Birnbaum J, Vervloet D (1998). "[Diagnosis of drug allergies]". Rev Mal Respir. 15 (6): 813–5. PMID 9923039.