Rifampin Hypersensitivity in a 2-year-old Child With Successful Rapid Oral Desensitization

Abstract

To the Editors: Management of tuberculosis is complicated by rising rates of drug-resistant disease for which there are limited therapeutic options.1 Rifampin is the only agent recommended for prophylaxis of isoniazid-resistant, rifampin-sensitive latent tuberculosis infection.2 We describe a child latently infected after household exposure to isoniazid-resistant tuberculosis who developed facial angioedema and pruritic rash within 30 minutes after ingesting the 5th dose of rifampin. Oral antihistamine was administered and symptoms resolved over 2 hours. Rifampin was discontinued. The child was assessed in a tertiary pediatric allergy clinic. Type I hypersensitivity to rifampin was ascertained based on the clinical history and confirmed with epicutaneous and intradermal testing (Table, Supplemental Digital Content 1, https://links.lww.com/INF/B831). The rifampin concentrations used for testing was based on a previously published report of nonirritant concentration of rifampin.3 Rapid desensitization to oral rifampin was performed and adapted from an accepted penicillin desensitization protocol.4 No premedication (antihistamine or corticosteroid) was administered. Incremental doses were administered orally every 15 minutes over a period of 3.25 hours on an inpatient pediatric ward (Table, Supplemental Digital Content 2, https://links.lww.com/INF/B832). The child continued with rifampin twice daily and completed a 3.5-month course of rifampin prophylaxis without adverse reactions before travel out of country. Adverse reactions to rifampin include fever, rash, flu-like syndrome, acute renal failure, hemolytic anemia, thrombocytopenia and anaphylaxis.5 Only a limited number of these effects are because of type 1 hypersensitivity or would be expected to respond to desensitization. Drug desensitization modifies a patient’s response to a drug that allows the patient to tolerate the drug for a temporary period in order for treatment to occur and lasts only for the duration of the treatment period. If the drug is discontinued and required in the future, the desensitization procedure must be repeated. The decision to pursue drug desensitization requires a high likelihood of drug allergy, a documented medical need for the drug, a lack of alternative agents and the benefits of drug desensitization outweigh the potential risks. Contraindications to desensitization include Steven-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, drug rash with eosinophilia and systemic symptoms, interstitial nephritis, hepatitis and hemolytic anemia.4 Our case highlights a rare case of rifampin hypersensitivity in a young child complicated by a lack of prophylaxis alternatives given the isoniazid-resistant strain of tuberculosis and crossreactivity among rifamycins.5 Rifampin desensitization protocols previously reported occurred mainly in adults involved premedication and were conducted in the intensive care unit. Premedication with antihistamine or corticosteroids was not used as these medications do not prevent IgE-mediated reactions and have the potential to mask early IgE symptoms at lower doses of the drug, thereby risking more serious reactions at higher doses. Drug desensitization should be performed under the guidance of an Allergy specialist, or at a minimum, a physician capable of treating anaphylaxis. The protocol outlined here may be a useful tool for other practitioners, particularly in areas where tuberculosis is endemic and treatment is essential. Kyla J. Hildebrand, MD, FRCP(C), MSc CH Department of Pediatrics Division of Allergy and Immunology University of British Columbia Vancouver Adelle Atkinson, MD, FRCP(C) Division of Allergy and Clinical Immunology Hospital for Sick Children Department of Paediatrics University of Toronto Ian Kitai, MB, BCh, FRCP(C)1 Division of Infectious Diseases Hospital for Sick Children and University of Toronto Toronto, Ontario, Canada