Increased Immunoglobulin (Ig) G4-Positive Plasma Cell Density and IgG4/IgG Ratio Are Not Specific for IgG4-Related Disease in the Skin

Objectives: Immunoglobulin (Ig) G4-related disease (IgG4-RD), a fibroinflammatory condition that can affect multiple organs, is suggested by lymphoplasmacytic inflammation, fibrosis, phlebitis, and increased IgG4+ plasma cell (PC) tissue density. In patients with suspected IgG4-RD and skin changes, skin biopsy may serve as a diagnostic screen or to supplement nondiagnostic visceral biopsy specimens. We aimed to determine whether increased cutaneous IgG4+ PCs or IgG4/IgG ratio is specific for IgG4-RD. Methods: We examined 50 mucocutaneous specimens representing seven PC-rich dermatoses and reactive PC-rich infiltrates with IgG and IgG4 immunohistochemical stains. Results: IgG4+ density exceeded 10 cells per high-power field in 22 (44%) of 50 specimens, representing six of seven diagnoses and reactive infiltrates. In five specimens (10%), the IgG4/IgG ratio exceeded 0.40. Conclusions: Moderately elevated IgG4+ PC density or IgG4/IgG ratio is a nonspecific finding in the skin. In cutaneous biopsy specimens showing increased IgG4+ PCs, careful consideration should be given to clinical, serologic, and other histopathologic features before attributing clinical changes to IgG4-RD.