Potential Dupilumab‐Induced Unmasking of Specific Immunoglobulin Deficiency: A First‐of‐Its‐Kind Case

Background Dupilumab, a monoclonal antibody targeting the interleukin‐4 receptor alpha subunit (IL‐4Rα), is approved for the treatment of various Th2‐mediated conditions such as atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. While its side effect profile is well‐established, its impact on humoral immunity and potential to unmask subclinical immunodeficiencies remains underexplored. Case Presentation We report a unique case of a 45‐year‐old woman with severe persistent asthma and chronic sinusitis who developed recurrent MRSA pneumonia and empyema after initiating dupilumab therapy. Initially treated with standard asthma therapies, she was started on dupilumab due to uncontrolled symptoms. One year into therapy, she developed a loculated empyema requiring surgical intervention. A second episode of MRSA empyema occurred 2 years later, necessitating further decortication. Her immunologic workup revealed a progressive decline in serum IgG levels (from 1100 to 851 mg/dL) and poor pneumococcal vaccine antibody responses, suggestive of impaired polysaccharide antibody response and possible specific antibody deficiency. Given the timing of immunologic decline in relation to dupilumab initiation and the known role of IL‐4 in B cell maturation and class‐switch recombination, we propose that IL‐4 blockade may have unmasked a previously subclinical immunoglobulin deficiency. Conclusion Our case suggests a potential association between dupilumab therapy and unmasking of specific antibody deficiency. IL‐4 plays a critical role in B cell survival and immunoglobulin class switching; thus, its inhibition may impair humoral responses in susceptible individuals. Clinicians should maintain a high index of suspicion for immunodeficiency in patients on dupilumab who present with recurrent infections. Further research is warranted to elucidate the immunologic consequences of IL‐4 blockade and to identify patients who may be at risk for developing secondary immunodeficiency.