Early-onset bibasilar emphysema in a patient with PLCG2-related immune dysregulation

Mutations in the PLCG2 gene, which encodes an enzyme in the intracellular signaling pathway of B lymphocytes, result in a spectrum of conditions involving frequent infections, antibody deficiencies, immune dysregulation, and cutaneous manifestations. These conditions are coined APLAID. We describe a case of early-onset bibasilar emphysema in an individual with frequent respiratory infections and immunoglobulin deficiencies, found to have a PLCG2 mutation on genetic testing. This case is unusual because the patient has bibasilar emphysema that is unrelated to alpha-1 antitrypsin deficiency, and because COPD is not a previously described manifestation of APLAID. The mechanism causing this phenotype is unclear; it is possible that frequent infections lead to lung parenchymal damage and emphysema, or perhaps there is an association between autoimmunity and emphysema. With this case, we expand the spectrum of PLCG2-related phenotypes, highlight the utility of genetic testing, and review the literature on possible treatment options including IVIG and corticosteroids.