Outcomes of Reintroducing Antituberculous Drugs Following Cutaneous Adverse Drug Reactions

Background: There are limited data about the outcomes of tuberculosis-associated cutaneous adverse drug reactions (CADR), particularly in HIV-infected patients. The reintroduction of first-line anti-tuberculous drugs after CADR is controversial and management is poorly defined.

Methods: We retrospectively reviewed the records of 298 patients with CADR admitted to the dermatology ward of a tertiary referral centre in Cape Town, South Africa.

Results: Tuberculosis-associated CADR was diagnosed in 65/298 patients. Of these, 60/65(92%) were HIV-infected (median CD4 count =107 cells/mm³). Antituberculous drugs were reintroduced in 46/65(71%) of patients, of whom 23/46(50%) developed reintroduction reactions. The most frequent reintroduction reactions were itch in 11/23(48%), hepatitis in 9/23(39%) and fever in 8/23(35%) of patients. Thirteen out of 23(57%) of the reintroduction reactions were mild, 6/23(26%) moderate and 4/23(26%) severe.  Amongst those with reintroduction reactions, rifampicin was the offending drug in 13/23(57%), isoniazid in 5/23(22%), pyrazinamide in 3/23(13%) and ethambutol, streptomycin and ofloxacin each in 1/23(4%) cases. Only lack of previous tuberculosis treatment [adjusted odds ratio (OR) = 17.03, 95%CI 1.90-153.27, p = 0.01) and rechallenge with rifampicin (adjusted OR = 26.3, 95%CI 2.76-251.8, p= 0.005) were independently associated with the likelihood of reintroduction reaction.

Conclusions: In this high tuberculosis burden African setting, although reintroduction reactions are common, the majority are non-life threatening. All the first-line antituberculous drugs can cause CADR and rifampicin is more commonly implicated than previously reported.  These data guide the management of antituberculous drug-associated CADR in high HIV-prevalence settings.