Involvement of two or more sets of lacrimal glands and/or major salivary glands is related to greater systemic disease activity due to multi-organ involvement in IgG4-related dacryoadenitis/sialadenitis.

OBJECTIVES: In IgG4-related dacryoadenitis and/or sialadenitis (IgG4-DS), involvement of two or more sets of lacrimal glands (LGs) and/or major salivary glands (MSGs) is regarded as a specific finding with diagnostic significance. This study aimed to clarify the influence of this factor on the overall clinical picture of IgG4-DS. METHODS: We retrospectively reviewed the medical records of 130 patients with IgG4-related disease, 97 of whom were diagnosed with IgG4-DS. We determined their clinical features according to the presence/absence of involvement of ≥2 sets of LGs and/or MSGs and compared the results with those obtained in 33 DS-limited patients. RESULTS: The IgG4-DS patients comprised 60 men and 37 women (median age 65 years). The median serum IgG4 level at diagnosis was 548 mg/dL. The patients with involvement of ≥2 sets (n = 44) had significantly more affected organs, lower serum C3 and C4 levels, and a tendency to have higher serum IgG levels and IgG4-RD responder index than did those without it (n = 53). In the 33 DS-limited patients, these two groups had no significant differences in clinical features. CONCLUSIONS: Involvement of ≥2 sets of LGs and/or MSGs suggests greater systemic disease activity mainly reflected by involvement of more organs.

IgG4-related Dacryoadenitis and Sialadenitis with Palatal Gland Swelling.

Many cases of immunoglobulin G4-related disease (IgG4-RD) involve swelling of the salivary glands, often affecting the parotid and submandibular glands in the head and neck region, in addition to the lacrimal glands. Cases of IgG4-RD characterized by swelling of the palatal glands, however, are extremely rare. Here, we describe a case of IgG4-RD involving bilateral swelling of the palatal glands. An 83-year-old man presented at our hospital with bilateral swelling of the lacrimal and submandibular glands. A solid bilateral swelling of normal colour and unclear boundaries was observed in the hard palate. The lesion was diagnosed as IgG4-RD and steroid therapy initiated. A subsequent decrease in swelling of the palatal, lacrimal, and submandibular glands was confirmed by magnetic resonance imaging. These results indicate that dentists should suspect IgG4-RD in patients presenting with bilateral swelling of the palatal glands.

The diagnostic utility of submandibular gland sonography and labial salivary gland biopsy in IgG4-related dacryoadenitis and sialadenitis: Its potential application to the diagnostic criteria.

Objectives: In this study, we investigated the diagnostic utility of submandibular gland (SMG) sonography and labial salivary gland (LSG) biopsy as a less invasive procedure for diagnosing IgG4-related dacryoadenitis and sialadenitis (IgG4-DS)Methods: Sixty-eight patients with suspected IgG4-DS by presenting swelling of elevated serum IgG (>1747 mg/dl) and/or swelling glands underwent SMG sonography, LSG biopsy and measurement for serum IgG4. SMG sonographic diagnosis was determined by the following characteristic changes; 'hypoechoic areas of a nodal pattern with high vascularity' and/or 'hypoechoic areas of a reticular pattern in the superficial part'.Results: Thirty-one patients were diagnosed with IgG4-DS, 5 with IgG4-RD unaccompanied by lacrimal and salivary gland lesions, 28 with Sjögren's syndrome, and 4 with malignant lymphoma. The sensitivity, specificity, and accuracy of SMG sonography and LSG biopsy were 100%, 83.8%, 91.2% and 64.5%, 73.8%, 75.0%, respectively. Moreover, those of SMG sonography and LSG biopsy combined with serum IgG4 concentration (>135 mg/dl) were 100%, 94.6%, 97.1% and 64.5%, 91.9%, 79.4%, respectively.Conclusion: LSG biopsy needs to be extremely careful to diagnose IgG4-DS because of its low sensitivity. SMG sonography is sufficient for the diagnosis of IgG4-DS, especially when combined with serologic analysis. Thus, SMG sonography could adapt to the diagnostic criteria of IgG4-DS as a non-invasive method.

The role of cytotoxic T cells in IgG4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease.

OBJECTIVES: Immunoglobulin (Ig) G4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease (MD), is a chronic inflammatory disease. However, little is known about its pathogenesis and pathological condition. In the present study, we used immunohistological techniques to compare the roles of cytotoxic T lymphocytes (CTLs) in MD and primary Sjogren's syndrome (SS). We examined the state of CTLs [cytotoxic granule-positive rate and programmed death-1 (PD-1) expression rate] in the salivary glands. METHODS: The study samples comprised 12 submaxillary glands from untreated MD patients and 12 labial glands from SS patients. We performed immunofluorescence and multicolor immunofluorescence to stain CD8, perforin (PRF), granzyme B (GZMB), and PD-1. We measured the total number of CTLs as well as the PRF(+)CTLs, GZMB(+)CTLs, and PD-1(+)CTLs. RESULTS: We found that the degree of infiltration of CTLs was equal in MD and SS, but the rate of CTLs with cytotoxic granules, especially PRF, in MD was less than in SS. In addition, the frequency of PD-1(+)CTLs in MD was higher than that in SS. CONCLUSIONS: Cytotoxic granule-positive CTLs were in the minority in D salivary glands, and this regulation might relate to PD-1 signals like the state of exhaustion and anergy.

Relapse patterns and predictors of IgG4-related diseases involved with autoimmune pancreatitis: A single-center retrospective study of 115 patients.

OBJECTIVE: Autoimmune pancreatitis is an autoimmune disorder accompanied by clinicopathological manifestations that have been established as immunoglobulin (IgG)4-related diseases (IgG4-RD). Other IgG4-RD are often involved with autoimmune pancreatitis. They sometimes relapse despite a favorable response to steroid therapy. This study aimed to clarify the patterns and risk factors for extrapancreatic relapse. METHODS: We reviewed the data of 115 patients diagnosed with definite autoimmune pancreatitis type 1 and followed up for > 1 year. We analyzed two items: the timing and pattern of extrapancreatic relapse, and risk factors for relapse with three common manifestations: IgG4-related sclerosing cholangitis (SC), IgG4-related dacryoadenitis and sialadenitis (DS), and IgG4-related retroperitoneal fibrosis (RF). RESULTS: Remission was achieved in all patients, except one. The extrapancreatic relapse rates were 11.0%, 19.7%, and 40% within 3, 5, and 10 years, respectively. Of 26 patients with extrapancreatic relapse, nine (34.6%) relapsed with a new IgG4-RD. Based on multivariate analysis, the interval between symptom onset and steroid initiation, and the presence of RF at onset were significant risk factors for relapse with SC and RF, respectively. CONCLUSIONS: Our results indicate that they may be various extrapancreatic relapse patterns especially in autoimmune pancreatitis with other organ involvement. Patients with a delayed initiation of steroids or RF at onset should be carefully followed up as high-risk groups for SC and RF relapse.