Antituberculosis drug-induced non-blistering systemicsevere reactions: A 10-year (2012-2022) literature review

Angela Rizzi,^1,† Eleonora Nucera,^1,2,† Sara Urbani,¹ David Longhino,¹ Franziska Michaela Lohmeyer,³
Giovanni Gambassi,^2,4 Luca Gammeri,⁵ Sebastiano Gangemi,^5,∫ Riccardo Inchingolo^6,∫

Affiliations:
¹ UOSD Allergologia e Immunologia Clinica, Dipartimento Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
² Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
³ Direzione Scientifica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
⁴ Division of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
⁵ Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, Messina, Italy
⁶ UOC Pneumologia, Dipartimento Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

^†Angela Rizzi and Eleonora Nucera contributed equally to this work as co-first authors.
^∫Sebastiano Gangemi and Riccardo Inchingolo equally contributed and are co-last authors

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) and drug-induced liver injury (DILI) can hamper therapeutic strategy, contribute to multiple drug resistance and serious public health burden. Diagnosis (including allergy assessment) and management of these two severe hypersensitivity reactions in clinical practice are somewhat difficult and published scientific evidence is rather weak and limited. The first step is always represented by stopping all anti-tuberculosis (TB) drugs, treating reaction with systemic corticosteroids, and identifying the offending drug, even if it is often complicated by the patient’s simultaneous intake of antibiotics. Patch tests and in vitro tests, such as lymphocyte transformation test, could bridge this diagnostic gap, but the available data are scarce and their sensitivity low. The re-challenge test is often necessary but places patients at risk for serious adverse reactions. The desensitization protocols are quite varied and not universally accepted. In this narrative review, we provide an update to the literature data on the management of DRESS and DILI with particular attention to the allergological work-up in the last decade.
Key words: Antituberculosis drugs, systemic severe reactions, Drug Reaction with Eosinophilia and Systemic Symptoms, drug-induced hypersensitivity syndrome, Drug-Induced Liver Injury, T-cell-mediated hypersensitivity, allergological management, re-challenge, desensitization