title: Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.
abstract: BACKGROUND
  The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied.
  
  
  OBJECTIVE
  To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection.
  
  
  METHODS
  Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated.
  
  
  RESULTS
  Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions.
  
  
  CONCLUSIONS
  In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings.
authors.affiliation: Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.|Lung Infection and Immunity Unit, Division of Pulmonology, University of Cape Town, Cape Town, South Africa.|Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: R J
authors.initials: RJ
authors.lastname: Lehloenya
authors.affiliation: Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: Todd
authors.affiliation: Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Wallace
authors.affiliation: Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: M R
authors.initials: MR
authors.lastname: Ngwanya
authors.affiliation: Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Muloiwa
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology, University of Cape Town, Cape Town, South Africa.|Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: K
authors.initials: K
authors.lastname: Dheda
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D060085:Coinfection / Q000150:complications*; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D010328:Patch Tests; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis / Q000209:etiology; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents