Rifampicin (also known as rifampin) is one of the most potent first-line antituberculosis drugs and an indispensable treatment option for isoniazid-resistant, rifampicin-sensitive tuberculosis (TB). Hypersensitivity reactions to rifampicin, mainly including fever, flu-like syndrome, rash, thrombocytopenia, acute renal failure, urticaria, and anaphylaxis, are considered rare but may occur among susceptible individuals and lead to premature discontinuation of the drug. Drug desensitization is a well-established procedure that may temporarily modify a patient’s immunologic response to the sensitizing agent, thus allowing for continuation of treatment. Desensitization to rifampicin has been previously described in rare case reports, almost invariably with successful results. We herein report a case of anaphylaxis during rapid oral desensitization to rifampicin in a male patient with active TB and a history of anaphylactic reactions to this agent. To the best of our knowledge, this is the first report in the English literature of a severe immediate-type reaction during desensitization to rifampicin. A 72-year-old man presented to the outpatient pulmonary clinic of “Sotiria” General Hospital, Athens, Greece, with fever, nonproductive cough, and weakness, lasting for 2 weeks. His medical history was significant for adult-onset diabetes mellitus and rheumatoid arthritis, treated with metformin and low-dose prednisone and intravenous infliximab, respectively. The patient was diagnosed with miliary TB and was started on anti-TB treatment with isoniazid (300 mg/day), rifampicin (600 mg/day), pyrazinamide (1500 mg/day), and ethambutol (1200 mg/day). Within 2 weeks after initiation of the above regimen, and 30 minutes after administration of the last dose of rifampicin, the patient developed fever and widespread urticaria; all drugs were subsequently discontinued and gradually reintroduced—after resolution of the cutaneous reaction—to identify the culprit drug. Urticaria, palmoplantar, and oropharyngeal pruritus were noted within 5 minutes after reintroduction of rifampicin and the drug was stopped; rifampicin was thereafter replaced with rifabutin. Ten days after initiation of rifabutin, the patient developed a maculopapular rash that affected the trunk and lower extremities. A skin biopsy was compatible with drug-induced eruption and rifabutin was discontinued. Approximately 3 years after his initial diagnosis of TB, the patient developed recurrent TB and was again started on a multidrug anti-TB regimen comprising isoniazid, rifabutin, pyrazinamide, and ethambutol. Twelve days after initiation of treatment a maculopapular rash appeared on the patient’s upper and lower extremities; rifabutin was again discontinued, followed by gradual resolution of the eruption, and the patient was referred to the Allergy Department of our hospital for further evaluation and management. At the time of the patient’s presentation to our department, skin prick test (SPT) and intradermal (ID) skin testing to rifampicin were performed, based on previous recommendations defining the highest nonirritant intradermal skin concentration of rifampicin (0.002 mg/mL). Histamine and saline were also used as positive and negative controls, respectively. SPT at a concentration of 2 mg/mL was negative, whereas a positive reaction (with a wheal of 15 17 mm and a flare of 42 44 mm) was shown on ID skin testing at a concentration of 0.002 mg/ mL. After obtaining the patient’s informed consent, oral desensitization to rifampicin was carried out in the intensive care unit. Premedication with antihistamines or steroids was not used (prednisone was discontinued for 3 days before the procedure) because these drugs may mask initial symptoms of anaphylaxis during desensitization, as previously emphasized, and the patient was not taking b-blockers or angiotensin-converting enzyme inhibitors. Increasing dosages of rifampicin were administered every 30 minutes, at a starting dose of 0.0002 mg followed by gradual dose escalation (Table I), as described in previously published desensitization protocols. Twenty minutes after administration of the 50 mg rifampicin dose, the patient started complaining of pruritus of the palms, soles, and groin followed by facial and trunk erythema, cough, generalized urticaria, hypotenstion, and sinus tachycardia followed by sinus bradycardia (without other ECG abnormalities). The desensitization procedure was discontinued, and the patient was treated with IV fluids, oxygen and nebulized salbutamol, intramuscular adrenaline, and intravenous methylprednisolone, dimetindene and ranitidine, with gradual recovery. Serum tryptase obtained at 1 hour after the onset of symptoms was 25 mg/L. Repeat serum tryptase, measured 1 week later, was found to be within normal limits (4 mg/L). Given the patient’s anaphylactic reaction during rapid desensitization, anti-IgE treatment and desensitization to rifampicin using slow dose increment over several days were recommended but the patient refused. Hypersensitivity reactions to anti-TB agents are relatively uncommon, encountered in approximately 4%-5% of the treated population, but may as well lead to withdrawal of the culprit drug and switching to an alternative agent. Rifampicin, in particular, is generally considered a well-tolerated drug with a low percentage of adverse events, especially when administered in usual therapeutic doses and outside the context of HIV infection. Delayed reactions, including a variety of cutaneous manifestations, are the commonest adverse reactions induced by rifampicin, whereas severe immediate reactions, such as anaphylaxis, are exceedingly rare.
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Feb 17, 2016
Mohammad A E Faramawy + 4
Open Access
