Pyoderma Gangrenosum in a Patient with Bruton's X-linked Agammaglobulinemia: Shared Pathogenesis of Altered Tumor Necrosis Factor Alpha?

ABSTRACT

Individuals with Bruton's X-linked agammaglobulinemia (XLA) inherit a defect in the Btk gene, critical for B-cell differentiation. As a result, there is an absence of mature B-cells in the peripheral circulation with a marked reduction in serum levels of all immunoglobulin subtypes, predisposing patients with XLA to recurrent bacterial infections. Btk also functions in myeloid and dendritic cells, specifically in Toll-like receptor (TLR) signaling. TLRs are important in the recognition of foreign pathogens and elaboration of cytokines, such as tumor necrosis factor alpha (TNF-α). This suggests that the pathophysiology of XLA involves additional and unexplored immune dysregulation. The coexistence of pyoderma gangrenosum (PG) in a patient with Bruton's XLA has been rarely reported. PG is an uncommon, ulcerating, neutrophilic dermatosis. Although its etiology is unknown, it is noninfectious and thought to involve abnormal immune and neutrophil responses. Anti-TNF agents have been effective in treating some patients with PG, suggesting TNF-α may play a role in the pathogenesis of PG. Here we report the association of PG and Bruton's XLA, and demonstrate the presence of TNF-α within the lesion of PG.