Gallium SPECT/CT in evaluation of IgG4-related disease: A case report and literature review.

BACKGROUND: The clinical picture of IgG4-related sclerosing disease (IgG4-RSD) may mimic lymphoma, and should be in the differential diagnosis of patients with this clinical picture. CASE SUMMARY: A 32-year-old female had recurrent swelling of both eyelids for more than 15 years. Examination revealed elastic, firm, swollen lacrimal glands about 2-3 cm in diameter that was not painful. Head and orbits magnetic resonance imaging (MRI) showed mass lesions over the bilateral lacrimal glands, submandibular glands, and left foramen of ovale. The differential diagnosis included lymphoid tissue, inflammatory masses, and lymphoma. Gallium single-photon emission computed tomography/computed tomography (SPECT/CT) showed uptake in the bilateral lacrimal glands, right parotid and bilateral submandibular glands, bilateral perirenal region, mediastinal, prevertebral, paraaortic, lumbar, bilateral pelvic (including internal iliac chain) lymph nodes, anterior aspect of right 3rd rib, and lateral aspect of left 6th rib. CT showed multiple enlarged lymph nodes in the mediastinum, right pulmonary hilum, prevertebral space of the thoracolumbar spine, retroperitoneal paraaortic area, bilateral parailiac areas, and bilateral perirenal spaces. Antinuclear and anti-SSA/SSB antibodies were negative, and the serum IgG4 level was 740 mg/dL (normal, 8-140 mg/dL). Right parotid gland biopsy showed abundant IgG4-positive plasma cells. Mikulicz disease (IgG4-related sclerosing disease) was diagnosed and she received glucocorticoid treatment. Follow-up CT and MRI showed with resolved eyelid swelling and perirenal mass lesions. Follow-up gallium scan was normal. CONCLUSION: Gallium SPECT/CT can be a useful tool for initial and follow-up evaluation of IgG4-RSD.

Concomitant occurrence of Mikulicz's disease and immunoglobulin G4-related chronic rhinosinusitis: a clinicopathological study of 12 cases.

AIMS: Concomitant occurrence of Mikulicz's disease (MD) and immunoglobulin (Ig)G4-related chronic rhinosinusitis (IgG4-related CRS) is extremely rare. We evaluated the clinicopathological features of MD patients with concomitant IgG4-related CRS (CRS-MD). METHODS AND RESULTS: Twelve CRS-MD patients were evaluated clinically and biopsy samples were taken from the lacrimal/salivary glands (n = 12) and nasal mucosa (n = 7) for assessment of IgG4-positive cells, using immunohistochemical techniques. Similarly, nine MD patients and 10 patients with common CRS were evaluated as controls. CRS-MD patients had higher serum IgG and IgG4 concentrations than MD patients (P < 0.05 for both). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis was prominent in the lacrimal/salivary glands in both groups; however, the magnitude of IgG4-positive plasma cells infiltration in the CRS-MD group was significantly higher compared to the MD group (P = 0.004). Similarly, evaluation of nasal mucosa revealed greater lymphocyte, plasma cell and eosinophil infiltration and lymphoid follicle formation, together with significantly higher IgG4-positive plasma cell infiltration in the CRS-MD group compared to the common CRS group (P = 0.004). CONCLUSIONS: Concomitant MD and IgG4-related CRS were characterized by a combination of IgG4-positive plasma cells infiltration in the lacrimal/salivary glands and the nasal mucosa and increased serum IgG4.

Case report of Mikulicz's disease: A modern concept of an old entity.

Introduction: Modern knowlegde defines Mikulicz´s disease as a part of immunoglobulin G4-related disease. The main feature is the presence of lymphoplasmacytic infiltrates, immunoglobulin G4 plasma cells positivity, distinctive storiform fibrosis and moderate eosinophilia. Case Report: A 59-years old male presented with a mild keratoconjuctivitis sicca and enlarged lacrimal and salivary glands during the last two years. Althought clinical presentation of the patient was typical, earlier testing did not pinpoint Mikulicz ´s disease. By typical clinical presentation, elevated serum immunoglobulin G4 level and histopathological finding of lacrimal glands tissue we diagnosed Mikulicz´s disease successfully treated with corticosteroid therapy. Conclusion: We reported the first case of IgG4-related Mikulicz´s disease in Serbia. Our report highlights IgG4-related Mikulicz` s disease as an important differential diagnosis with Sjögren`s syndrome and lymphoproliferative disease in rheumatological practice.

Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and sialadenitis (Mikulicz's disease) and for differentiating it from Sjögren's syndrome (SS), with an emphasis on sonography.

INTRODUCTION: The aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in the imaging features between IgG4-DS and Sjögren's syndrome (SS). METHODS: Thirty-nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were enrolled. Images of the parotid and submandibular glands obtained using sonography, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and maxillofacial radiologists randomly reviewed the arranged image sets under blinded conditions. Each observer scored the confidence rating regarding the presence of the characteristic imaging findings using a 5-grade rating system. After scoring various findings, diagnosis was made as normal, IgG4-DS or SS, considering all findings for each case. RESULTS: On sonography, multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and obscuration of submandibular gland configuration were detected mainly in patients with SS (median scores 4, 4 and 3, respectively). Reticular and nodal patterns were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT revealed a tendency for abnormal (18)F-FDG accumulation and swelling of both the parotid and submandibular glands in patients with IgG4-DS, particularly in the submandibular glands. On MRI, SS had a high score regarding the findings of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5). Sonography showed the highest values among the four imaging modalities for sensitivity, specificity and accuracy. There were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058) concerning accuracy. CONCLUSIONS: Changes in the submandibular glands affected by IgG4-DS could be easily detected using sonography (characteristic bilateral nodal/reticular change) and FDG-PET/CT (abnormal (18)F-FDG accumulation). Even inexperienced observers could detect these findings. In addition, sonography could also differentiate SS. Consequently, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, involves no radiation exposure and is an effective imaging modality.

Immunology of IgG4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4(+) plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed.

[Comparative study of clinical features between unilateral and bilateral orbital IgG4-related disease]. / Estudio comparativo de los hallazgos clínicos en la enfermedad orbitaria asociada a IgG4 con afectación unilateral vs. bilateral.

OBJECTIVE: Descriptive and comparative study of patients with orbital IgG4-related disease. MATERIAL AND METHODS: A review and analysis of the cases diagnosed with inflammatory orbital lesion related to IgG4 by the Ophthalmic Pathology Service in the Dr. Luis Sánchez Bulnes Hospital. RESULTS: A total of 9 cases were found, in which 66% were women, and with a mean age of 48 years and time to diagnosis of 2 years. Unilateral involvement was observed in 56% of cases. All the females experienced pain, and there was an optimal response to corticosteroid treatment in 100% of patients who required medical treatment (one case showed spontaneous resolution). In bilateral cases (44%), only 25% were female, and none had pain as a presenting symptom. Furthermore, 25% of these patients required a combination with immunosuppressants to control inflammation. CONCLUSIONS: Clinical presentation of patients with unilateral orbital IgG4-related disease differs from those with bilateral involvement.

Diagnostic criteria for IgG4-related ophthalmic disease.

Immunoglobulin G4 (IgG4)-related disease is a novel clinical entity characterized by infiltration of IgG4-immunopositive plasmacytes and elevated serum IgG4 concentration accompanied by enlargement of and masses in various organs, including the lacrimal gland, salivary gland, and pancreas. Recent studies have clarified that conditions previously diagnosed as Mikulicz disease as well as various types of lymphoplasmacytic infiltrative disorders of the ocular adnexa are consistent with a diagnosis of IgG4-related disease. Against this background, the diagnostic criteria for IgG4-related ophthalmic disease have recently been established, based on both the clinical and the histopathologic features of the ocular lesions. This article reviews these new criteria with reference to the comprehensive diagnostic criteria for IgG4-related disease for all systemic conditions reported in 2012.

Ocular adnexal IgG4-related disease: clinical features, outcome, and factors associated with response to systemic steroids.

PURPOSE: The aim of this study was to investigate clinical characteristics, outcome, and factors associated with response to systemic administration of steroids in patients with ocular adnexal immunoglobulin G4 (IgG4)-related disease. METHODS: This was a retrospective evaluation of 11 patients with histopathologically verified ocular adnexal IgG4-related diseases at a medical center in Taiwan between January 2006 and December 2012. Clinical features and outcome, including serial change of serum IgG4 and clinical factors related to response to steroids systemically were evaluated. RESULTS: Seven men and four women, mean age 54.5 years and mean follow-up of 33.5 months, were evaluated. Elevated serum IgG4 levels (>135 mg/dl) were observed in ten patients (91%). Lacrimal gland involvement was noted in eight (72.7%), followed by orbit, extraocular muscles, and eyelids. Seven patients (63.6%) had bilateral ocular lesions and eight (72.7%) had extraorbital involvement. Eight of ten patients who underwent systemic steroid treatment responded well in the early phase. Recurrence developed in five patients (45%), requiring repeat steroid therapy and adjunctive treatment. Median serum levels of IgG4 reduced from 540 to 101 mg/dl in ten patients after systemic corticosteroid administration. Patients with lower serum IgG4 and IgG4:IgG ratio at diagnosis were associated with poor response (p = 0.037). CONCLUSIONS: Ocular adnexal IgG4-related disease predominantly involved the lacrimal glands bilaterally and was usually associated with high serum IgG4 levels and multiple organ involvement. Most patients responded well to steroid therapy, which was accompanied by a marked decrease in serum IgG4.

Clinical relevance of Küttner tumour and IgG4-related dacryoadenitis and sialoadenitis.

OBJECTIVES: Küttner tumour (KT), so-called chronic sclerosing sialoadenitis, is characterised by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis independent of sialolith formation. However, recent studies have indicated that some patients with KT develop high serum levels of IgG4 and infiltration of IgG4-positive plasma cells, namely IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease. The aim of this study was to clarify the clinical and pathological associations between KT and IgG4-DS. MATERIALS AND METHODS: Fifty-four patients pathologically diagnosed with KT or chronic sialoadenitis were divided into two groups according to the presence or absence of sialolith (KT-S (+) or KT-S (-), respectively). RESULTS: There were no significant differences in the clinical findings, including the mean age, sex and disease duration, between the two groups. All patients in the KT-S (+) group showed unilateral swelling without infiltration of IgG4-positive plasma cells or a history of other IgG4-related diseases (IgG4-RD), while those in the KT-S (-) group showed bilateral swelling (37.5%), strong infiltration of IgG4-positive plasma cells (87.5%) and a history of other IgG4-RD (12.5%). CONCLUSIONS: These results suggest an association between the pathogeneses of KT-S (-) and IgG4-DS, but not KT-S (+).

The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease.

IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by serum IgG4 elevation and the infiltration of IgG4-positive plasma cells in glandular tissues. For definitive diagnosis of IgG4-DS, biopsies of local lesions are recommended to exclude Sjögren's syndrome (SS), malignant tumours, and similar disorders. In this study, we examined the diagnostic utility of submandibular gland (SMG) and labial salivary gland (LSG) biopsies in IgG4-DS. Fourteen patients presenting with swelling of the SMG (eight females and six males) underwent both SMG and LSG biopsies. The sensitivity, specificity, and accuracy of SMG biopsies were all 100.0%. In contrast, those of LSG biopsies were 69.2%, 100.0%, and 71.4%, respectively. Thirty-three out of 61 LSG biopsies (54.1%) from all 14 patients were positive for the diagnostic criteria of IgG4-DS (IgG4-positive/IgG-positive plasma cells >0.4). None of the patients experienced complications such as facial nerve palsy, sialocele, or hyposalivation. The IgG4/IgG ratio showed no significant correlation between the LSG and SMG. The final diagnosis was IgG4-DS in 13 patients and marginal zone B-cell lymphoma (MZL) in one. These results suggest that incisional biopsy of the SMG is useful and appropriate for the definitive diagnosis of IgG4-DS, while diagnosis by LSG biopsy alone requires more caution.

IgG4-related skin disease.

IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7).

The clinical characteristics of patients with IgG4-related disease with infiltration of the labial salivary gland by IgG4-positive cells.

OBJECTIVES: Mikulicz's disease (MD) is an immunoglobulin (Ig) G4-related disease with systemic symptoms. Submandibular gland (SMG) biopsy is recommended for patients with possible IgG4-related MD for accurate differential diagnosis; however, it is difficult for certain patients to undergo this procedure. In contrast, labial salivary gland (LSG) biopsy is more convenient. Here we present an analysis of patients with IgG4-related MD whose LSG specimens were infiltrated with abundant IgG4-positive plasma cells. METHODS: Sixteen patients diagnosed with IgG4-related MD underwent simultaneous SMG and LSG biopsies. We evaluated patients' serological and (18)F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography ((18)F-FDG-PET/CT) and grouped them as LSG+ (LSG specimens with > 40% IgG4-positive plasma cells/IgG-positive plasma cells, 11 patients) or LSG- (LSG specimens with < 40% IgG4-positive plasma cells/IgG-positive plasma cells, 6 patients). RESULTS: There were not significant differences in serum IgG and IgG4 levels between the two groups; however, serum concentrations of soluble interleuikin-2 receptor (sIL-2R) were significantly higher in the LSG+ group. All patients with increased (18)F-FDG uptake in their parotid glands were a part of the LSG+ group. CONCLUSIONS: When a SMG biopsy is not possible, the serum concentration of sIL-2R and (18)F-FDG-PET/CT findings may predict whether LSG biopsy will facilitate the diagnosis of IgG4-related MD.

Mechanisms and assessment of IgG4-related disease: lessons for the rheumatologist.

Recognition of IgG4-related disease as an independent chronic inflammatory disorder is a relatively new concept; previously, the condition was thought to represent a subtype of Sjögren's syndrome. IgG4-related disease is characterized by elevated serum levels of IgG4 and inflammation of various organs, with abundant infiltration of IgG4-bearing plasma cells, storiform fibrosis and obliterative phlebitis representing the major histopathological features of the swollen organs. The aetiology and pathogenesis of this disorder remain unclear, but inflammation and subsequent fibrosis occur due to excess production of type 2 T-helper-cell and regulatory T-cell cytokines. The disease can comprise various organ manifestations, such as dacryoadenitis and sialadenitis (also called Mikulicz disease), type 1 autoimmune pancreatitis, kidney dysfunction and lung disease. Early intervention using glucocorticoids can improve IgG4-related organ dysfunction; however, patients often relapse when doses of these agents are tapered. The disease has also been associated with an increased incidence of certain malignancies. Increased awareness of IgG4-related disease might lead to consultation with rheumatologists owing to its clinical, and potentially pathogenetic, similarities with certain rheumatic disorders. With this in mind, we describe the pathogenic mechanisms of IgG4-related disease, and outline considerations for diagnosis and treatment of the condition.

IgG4-related Mikulicz's disease associated with thyroiditis: a case report and review of the literature.

PURPOSE: To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis. CASE REPORT: We describe a 25-year-old Chinese man who presented with bilateral, painless swellings of the lachrymal glands, parotid glands, and thyroid nodules. The patient underwent left-sided dacryoadenectomy and the diagnosis of IgG4-related Mikulicz's disease was pathologically confirmed. The size of the right-sided lachrymal gland and parotid glands recovered fundamentally after one month of glucocorticoid therapy. CONCLUSION: IgG4-related Mikulicz's disease associated with thyroiditis should be considered in the differential diagnosis of bilateral swellings of lachrymal glands, salivary glands, and thyroid nodules. Surgical excision is recommended in order to treat the tumor and to ensure the pathological diagnosis. Glucocorticoid therapy should be considered in association with surgery after removal.

Clinical features of a new disease concept, IgG4-related thyroiditis.

OBJECTIVES: Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz's disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. METHOD: We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz's disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland. RESULTS: Among the 22 patients (19%) in our cohort who were found to have hypothyroidism [thyroid stimulating hormone (TSH) > 4 mIU/L], 11 patients had clinical hypothyroidism [free thyroxine (FT4) < 1 ng/dL] and 11 patients had subclinical hypothyroidism (FT4 ≥ 1 ng/dL). Serum concentrations of IgG, IgG4, circulating immune complex (CIC), and ß2-microglobulin (ß2-MG) were significantly higher in the hypothyroidism group compared with the remaining 92 euthyroid patients, and serum C3 concentration was significantly lower. After prednisolone treatment, TSH values had decreased significantly (p = 0.005) in this group and FT4 values had increased significantly (p = 0.047). CT images showed that the thyroid glands of patients with clinical hypothyroidism had a significantly greater volume than those of the euthyroid and other groups. Pathological analysis of one resected thyroid gland disclosed a focused lesion with infiltration of lymphocytes and IgG4-bearing plasma cells and loss of thyroid follicles. CONCLUSIONS: Thyroid lesions associated with hypothyroidism can be considered as a new disease termed IgG4-related thyroiditis. Awareness of this condition should lead to appropriate corticosteroid treatment that may prevent progression to a fibrous state.

IgG4-related systemic disease: an uncommon presentation for an uncommon disease.

IgG4-related systemic disease is an emerging disease process that manifests with a constellation of features, most commonly but not exclusive to swelling and tuberous growth in the lacrimal and salivary glands, potentially involving many other organ systems. This condition often prompts investigations into malignancy or needless radical surgical procedures. A 58-year-old male was presented to a rheumatologist after several biopsies were done that were suspicious for neoplasia, involving the lacrimal gland and lung. The diagnosis was confirmed when tissue from the lacrimal gland biopsy was reviewed with special stains for IgG4, performed at the Mayo Clinic. This patient is interesting because his disease included bilateral lacrimal glands--at different intervals, the submandibular glands, the lung, and the thyroid gland. His disease responded to immunosuppression. Literature has shown resolution of the tumors upon starting glucocorticoids or rituximab. Our patient was given a course of prednisone and methotrexate with normal follow-up CT chest and physical exam.

IgG4-related Mikulicz's disease is a multiorgan lymphoproliferative disease distinct from Sjögren's syndrome: a Caucasian patient and literature review.

OBJECTIVES: This paper aims to report a case of IgG4-related Mikulicz's disease with a systematic review. METHODS: The relevant English literature was searched using the keywords 'Mikulicz's disease' and 'IgG4'. Original and review articles were reviewed, and the clinical scenarios were exemplified with a case report. RESULTS: A 49-year-old Caucasian man presented with axillary lymphadenopathy and bilateral parotid/submandibular enlargement. A chest computerized tomography showed mediastinal lymphadenopathy, with low metabolic activity on the position emission tomography. A histopathological study showed an IgG4/IgG ratio of 75% in the plasma cells of the submandibular glands, associated with high levels of total serum IgG and IgG4. He had dry mouth, but minor salivary gland biopsy was negative without xerophthalmia. He had nasal obstruction and dyspnea, notably with supine position/cervical rotation, which substantially improved with glucocorticoid treatment. He had newly diagnosed diabetes mellitus with hyperlipasaemia and diffuse pancreatic swelling supportive of autoimmune pancreatitis. CONCLUSIONS: Our case report supports the literature that there are similarities between IgG4-related Mikulicz's disease and Sjögren's syndrome, but the differences are significant. IgG4-related Mikulicz's disease is a multi-organ lymphoproliferative disease distinct from Sjögren's syndrome.

IgG4-related autoimmune pancreatitis overlapping with Mikulicz's disease and lymphadenitis: a case report.

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is categorized as type 1 or type 2 according to the clinical profile. Type 1 AIP, which predominantly presents in a few Asian countries, is a hyper-IgG4-related disease. We report a case of IgG4-related AIP overlapping with Mikulicz's disease and lymphadenitis, which is rare and seldom reported in literature. A 63-year male from Northeast China was admitted for abdominal distension lasting for one year. He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo. He had a 2-year history of bilateral submandibular lymphadenopathy without pain. He underwent surgical excision of the right submandibular lymph node one year prior to admission. He denied any history of alcohol, tobacco, or illicit drug use. Serological examination revealed high fasting blood sugar level (8.8 mmol/L) and high level of IgG4 (15.2 g/L). Anti-SSA or anti-SSB were negative. Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation. Immunohistochemical stain for IgG4 demonstrated diffuse infiltration of IgG4-positive plasma cells in labial salivary gland and lymph node biopsy specimens. The patient received a dose of 30 mg/d of prednisone for three weeks. At this three-week follow-up, the patient reported no discomfort and his swollen salivary glands, neck lymph node and pancreas had returned to normal size. The patient received a maintenance dose of 10 mg/d of prednisone for 6 mo, after which his illness had not recurred.