Immediate Hypersensitivity to Rifampicin in 3 Patients: Diagnostic Procedures and Induction of Clinical Tolerance

Abstract

Background: Desensitization with drugs may be indicated in some clinical situations. Apart from large experiences with β-lactam antibiotics and cotrimoxazole in HIV infection, experience with other drugs is limited. Rifampicin may elicit exanthema and urticaria, and their pathomechanisms are not known in detail. Since therapy with rifampicin may be indispensable in mycobacterial infections or against multiresistant Staphylococcusaureus, desensitization may be indicated in some patients. Objective: Report of immediate hypersensitivity to rifampicin and description of diagnostic and desensitization procedures. Methods: We report 3 patients with immediate urticarial reactions to rifampicin. Diagnostic procedures included skin and in vitro tests (specific IgE, lymphocyte transformation test, LTT, and CAST^®). The non-irritant cutoff concentration was evaluated in 24 volunteers. A 7-day desensitization procedure was used. Results: Only intradermal tests at a dilution of at least 1:10,000 (concentration of rifampicin approximately 0.006 mg/ml) were true positive, whereas in vitro tests (IgE, LTT and CAST) did not correctly identify hypersensitive patients. Two patients had positive accidental reexposure. All patients were successfully desensitized with rifampicin according to a slow 7-day protocol. Conclusions: Rifampicin rarely elicits immediate hypersensitivity symptoms which may be diagnosed by intradermal skin tests. In vitro tests did not contribute to the diagnosis. Therefore, an IgE-mediated mechanism remains to be proven. Desensitization with rifampicin using different protocols has been reported. In our 3 cases, clinical tolerance to rifampicin was achieved using a 7-day protocol.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

“…Successful rapid oral desensitization regimes [26] have been described for INH [26, 27, 28, 29, 30, 31, 32], RIF [26, 27, 28, 29, 33, 34, 35], EMB [28, 29], and PZA [29, 36]. The initial (index) reaction in all cases usually involve combinations of REHZ, with the reactions ranging from cutaneous drug eruptions alone to organ-specific/systemic manifestations.…”

“…skin prick test (SPT) for INH [28, 29, 36], RIF [28, 29, 33, 35, 36], EMB [36], PZA [36]SPT and intradermal tests for INH and RIF [27, 28, 29]cellular allergen stimulation tests for RIF-specific IgE [35]LTT for INH [17, 30, 31], RIF [17, 30, 34], EMB [17], PZA [17, 30]DPT for INH [30, 31, 32]. …”

Update on the Management of Antibiotic Allergy

“…In practice, it is often not clinically feasible to leave MTC infection untreated for 6 weeks pending evaluation using LTT or patch tests, which in the end may not be helpful. As such, rapid oral desensitization regimes have been described for isoniazid, rifampicin and ethambutol 107-111. These regimes often involve reintroducing the anti-tuberculous drugs as soon as the allergic reaction has settled.…”

Place of Drug Skin Tests in Investigating Systemic Cutaneous Drug Reactions

“…Prick tests and IDT have also been performed with other drugs such as local anesthetics (all negative in 236 patients, with only one localized reaction among 236 subcutaneous challenges [109,110] ), carboplatin (126 patients tested) [42] or platin salts [43] , clindamycin (2 delayed positive reactions/31 tested patients) [111] , corticosteroids [72,112] , dexchlorpheniramine (immediate positivity in 1 case) [113] , estradiol [3] , gadoterate meglumine [114] , heparin derivatives [38,[49][50][51][52] , insulin [115,116] , quinolones [95,117] , radiocontrast media [44,[46][47][48] , rifampicin (3 cases and 24 controls) [118,119] , and synergistins [40] with 3 positive results on 9 prick tests and 4/5 delayed positive results on IDT.…”