Clinicopathological characteristics of immunoglobulin G4-related sialadenitis

Abstract

IntroductionImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical assessment were studied to clarify the clinicopathologic characteristics of the salivary glands involved in IgG4-RS, especially the relationship between the histopathologic features and function of salivary glands or serum levels of IgG4.MethodsClinical, serologic, imaging and histopathological data of these cases were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were calculated. The saliva flow rate was measured. Scintigraphy with 99mTc-pertechnetate was undertaken in 31 cases, and the concentration index (CI) and secretion index (SI) was calculated. Relationships between fibrosis severity and salivary gland function or serum IgG4 levels were analyzed.ResultsThe first symptom was swelling of bilateral submandibular or lacrimal glands. Physical examination showed multiple bilateral major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS. Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at rest was lower than normal in 34 cases; stimulated saliva flow was lower than normal in 15 cases. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum IgG4 level was higher and saliva secretion lower as glandular fibrosis increased.ConclusionsProminent changes in the morphology, histology, immunohistochemistry and secretion of the major salivary glands of IgG4-RS patients were accompanied by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE, allergic history, eosinophil infiltration suggest allergic reactions as a potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with salivary function and serum levels of IgG4.

Sialendoscopic management of autoimmune sialadenitis: a review of literature

“…Identification of IgG4-positive plasma cells in both KT and MD propelled renewed interest in these diseases, and fueled re-analyses of the classification of inflamed salivary glands 56 .…”

IgG4‐related sialadenitis and Sjögren's syndrome

“…IgG4‐RS and SS have differences and similarities regarding their clinical, serological and histopathological characteristics (Table ). Both IgG4‐RS and SS affect middle‐aged individuals, yet IgG4‐RS and systemic IgG4‐RD occur more frequently in males than females (Li et al , ). To date, diagnostic criteria regarding IgG4‐RS have not yet been established, and in relevant publications, the clinical spectrum of IgG4‐RS presents a great heterogeneity.…”

“…Xerostomia, encountered less frequently in IgG4‐RS (30%) than SS, is a finding depicted by decreased saliva flow rates (stimulated or not) and by 99m Tc‐pertechnetate scintigraphy revealing reduced secretory function of submandibular (more severe) and parotid glands. (Li et al , ).…”

“…In 40% of patients with AIP, IgG4‐RS can coexist synchronously or metachronously. On the other hand, patients with IgG4‐RS suffer more frequently (15–30%) from AIP, sclerosing cholangitis, and asthma, compared to the primary SS counterparts (Moriyama et al , ; Mavragani et al , ; Li et al , ). Nose, paranasal sinuses, and ears are also very often (>50%) involved along with the salivary and lacrimal glands in IgG4‐RS (Hong et al , ).…”

“…Historically, bilateral parotid and lacrimal gland enlargement was termed Mikulicz's disease (MD); it was considered to be either idiopathic or secondary to tuberculosis, sarcoidosis, lymphoma, or Sjögren's syndrome (SS) as the two entities have similar histopathological picture. In the recent definition of IgG4‐RD, the formerly termed MD and the isolated submandibular gland enlargement (formerly known as Kuttner's tumor or sclerosing sialadenitis) are now classified as subcategories of IgG4‐related sialadenitis (IgG4‐RS) (Li et al , ).…”