The value of skin testing with tumor necrosis factor-inhibitors in patients with local and systemic hypersensitivity reactions

<b>Background:</b> Hypersensitivity reactions (HSR) to tumor necrosis factor α inhibitors (TNFi) can occur but data about skin testing in such reactions are limited. <b>Objective:</b> To evaluate skin testing in patients with HSRs to TNFi. <b>Methods:</b> A detailed review of demographics and clinical characteristics, features of index reactions, results of skin tests, and outcomes of desensitization protocols were obtained. <b>Results:</b> The cohort comprised 64 patients (women/men: 41/23). Treatment distribution included etanercept (n = 50 [78.1%]), adalimumab (n = 11 [17.2%]), and infliximab (n = 3 [4.7%]). HSRs were seen as an injection-site reaction (ISR) in 47 patients (73.4%), generalized urticaria in 8 patients (12.5%), and anaphylaxis in 3 patients (4.7%). Forty-four patients (44/64 [72%]) had positivity on skin tests as either skin-prick test (SPT) or intradermal test (IDT). Among other reaction types, the patients with ISRs exhibited the highest skin test positivity (p = 0.043). Among the 17 patients who underwent rapid subcutaneous or intravenous desensitization, 15 patients (88.2%) had positive skin test results, and all desensitization procedures were successfully completed, despite some experiencing local breakthrough reactions (BTR). <b>Conclusion:</b> This study, which includes the largest number of patients reported in the literature, highlights the important role of skin testing in diagnosing HSRs to TNFi. Notably, etanercept demonstrated the highest positivity rate. Successful completion of desensitization protocols despite some BTRs highlights the importance of desensitization in patients experiencing HSRs to these treatments.