Sjögren’s Syndrome, IgG₄-Related Disorders

Abstract

Sjögren’s syndrome (SS) is a chronic, systemic autoimmune disorder affecting predominantly middle-aged females. SS clinical manifestations can be related to glandular dysfunction (keratoconjunctivitis sicca, oral dryness, bronchitis sicca, parotid gland enlargement) and extra-glandular/systemic involvement. The latter is either due to peri-epithelial infiltrates in parenchymal organs (small airway disease, interstitial nephritis, biliary cirrhosis) or due to immune complex deposition (palpable purpura, peripheral neuropathy, glomerulonephritis, systemic vasculitis). In the majority of patients, SS runs an indolent benign course. In a small yet not negligible number of cases (5–10%), SS is complicated by lymphoid neoplasia. Sicca manifestations, increased fatigability, arthralgias/myalgias, nonerosive arthritis, Raynaud’s phenomenon (RP), and signs of renal tubular acidosis may be initial manifestations of SS. After excluding other causes of sicca symptomatology, patients should be assessed for lacrimal and salivary gland function (ocular staining with lissamine green or rose bengal, Schirmer’s test and unstimulated saliva secretion, respectively), and a biopsy of labial minor salivary glands should be performed to evaluate the presence of lymphocytic infiltrates around salivary gland epithelium. SS patients presenting salivary gland enlargement, Raynaud’s phenomenon, lymphadenopathy, anti-Ro/SSA or anti-La/SSB autoantibodies, rheumatoid factor positivity, monoclonality, and low serum C4 levels should be monitored closely, since these clinical, laboratory, and immunologic parameters have been shown to be independent predictors for non-Hodgkin’s lymphoma development.

IgG4-related disease (IgG4-RD) has recently emerged as a new clinical entity. It comprises numerous conditions previously thought to be unrelated, such as sclerosing dacryoadenitis/orbital pseudotumor, sialadenitis, autoimmune pancreatitis, retroperitoneal fibrosis/periaortitis, sclerosing cholangitis, Riedel thyroiditis, hypophysitis, and prostatitis. IgG4-RDs are clinically characterized by tumor-like lesions in affected organs. Histopathologically, they typically present lymphoplasmacytic infiltrates with increased IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis, and tissue eosinophilia, while serum IgG4 concentration is usually increased. Typically IgG4RD symptoms respond promptly to steroids.