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

BACKGROUND: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. OBJECTIVE: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. METHODS: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. RESULTS: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. CONCLUSION: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.

Outcomes of chronic hepatitis B infection in Oriental patients with rheumatic diseases

<p><b>INTRODUCTION</b>The aim of this study was to ascertain the outcomes of chronic hepatitis B (CHB) infection following immunosuppressive therapy in 38 consecutive oriental patients with systemic rheumatic diseases.</p><p><b>MATERIALS AND METHODS</b>This is a retrospective consecutive, non-comparative study.</p><p><b>RESULTS</b>The majority of patients were female (26, 68.4%), predominantly Chinese (92.1%), with a mean age 54 +/- 14 years (range, 16 to 87). The mean duration of rheumatic disease was 9 +/- 11 years (range, 0.1 to 48), with rheumatoid arthritis (52.6%) and systemic lupus erythematosus (23.7%) being the most common. The mean duration of CHB infection was 6 +/- 5 years (range, 0.1 to 17), with the majority diagnosed during pre-methotrexate screening (50.0%) and asymptomatic transaminitis following initiation of immunosuppressive therapy (23.7%). Upon diagnosis of rheumatic disease, all patients had normal alanine aminotransferase (ALT). Of these, 18.2% were positive for hepatitis B e antigen (HBeAg) and 78.1% were positive for anti- HBe antibody. Twenty (52.6%) developed ALT elevation, which was more than twice the upper limit of normal in 12 patients. ALT normalised spontaneously in 12 patients without hepatic decompensation or change in therapy. Seven (18.4%) patients received lamivudine for 18 +/- 22 months (range, 2 to 61). Two patients developed YMDD mutation subsequently treated with adefovir (1) and adefovir/lamivudine (1). There were 3 (7.9%) hepatitis B virus (HBV)-unrelated deaths [infection (2), genitourinary malignancy (1)], and 1 from HBV-reactivation complicated by septicaemia. None have developed hepatocellular carcinoma.</p><p><b>CONCLUSION</b>Elevated ALT occurred in 52.6% of patients, with only 18.4% requiring anti-viral therapy for HBV reactivation. HBV-related mortality was low. With the appropriate precautionary measures, prednisolone and immunosuppressants (except methotrexate and leflunomide) may be used safely in patients where clinically indicated.</p>