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Effective treatment for drug-sensitive TB remains a long, multidrug endeavor. Therapeutic complexity is increased by HIV coinfection (>60% of incident TB cases are co-infected in HIV/TB endemic settings) and the growing burden of multi- and extremely drug-resistant TB (MDR- and XDR-TB). CADRs are common adverse reactions in both drug-sensitive and resistant anti-TB regimens, and the majorities are delayed T-cell-mediated reactions. Individual anti-TB drugs cause different CADR phenotypes of varying severity, while SCAR phenotypes such as DRESS, SJS/TEN, and LDE have been associated with many chemically different anti-TB drugs. The key management challenges include (1) multiple possible offending drugs, with a lack of accurate diagnostic testing, (2) high TB-related mortality with prolonged treatment interruptions, and (3) not unnecessarily excluding effective non-culprit anti-TB drugs in CADR patients. We discuss the spectrum of anti-TB drug-associated CADRs and offending drugs, as well as the pragmatic utility of drug provocation testing to identify culprit drugs and minimize treatment interruptions.

Here we will review some breakthroughs in science and translational medicine that are shaping the field of adverse drug reactions (ADR), including cutaneous adverse drugs reactions (CADR) and the subcategory of severe cutaneous adverse reactions (SCAR). This includes the discovery of multiple new associations (genetic and beyond) yielding insight into mechanisms of disease pathogenesis. Further advances will come from personalized/precision medicine initiatives looking at how an individual’s unique combination of genome, epigenome, transcriptome, proteome, metabolome, phenome, and exposome predisposes them to CADR. Multiple disciplines of “omics” (i.e., genomics, epigenomics) stand to contribute to the field. The ultimate goals of CADR research are to improve diagnosis and treatment, but also prevention of disease by predicting reactions before medications are given and before new drugs are developed and used in man.

CADR is more common in HIV-infected persons, although the incidence is declining because of the new safer drugs and early initiation of antiretroviral therapy. The presentation and clinical course does not seem to differ from that in the general population. Antiretrovirals, antituberculosis drugs, and drugs for treating opportunistic infections are most commonly implicated. HIV-associated CADR poses major diagnostic and management challenges because of polypharmacy, overlapping drug toxicities, drug interactions, overlap of CADR with other diseases, and limited alternative drugs. We discuss pragmatic management strategies of HIV-associated CADR focusing on resource-limited settings, where HIV infection and associated CADR are most common.