BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
METHODS: A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz\'s disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size.
CONCLUSIONS: Mikulicz\'s disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

BACKGROUND: Sjögren\'s Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz\'s disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis.
METHODS: A 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer\'s test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS.
CONCLUSIONS: When the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD.

Immunoglobulin G4-related disease (IgG4-RD) is a recently established systemic disease that is characteristically associated with elevated serum immunoglobulin G4 (IgG4) levels and believed to be caused by autoimmune mechanisms. The clinical features of IgG4-RD include (i) systemic distribution, (ii) imaging findings of swelling, nodules, and/or wall thickening, (iii) high serum IgG4 levels, (iv) abundant IgG4-bearing plasma cell infiltration and fibrosis in affected organs, (v) a favorable response to corticosteroid therapy, and (vi) coexistence with other IgG4-RD manifestations simultaneously or in a metachronous fashion. The concept of IgG4-RD was established based on the culmination of specific discoveries. Specifically, a close association between autoimmune pancreatitis (AIP) and high serum IgG4 levels, massive IgG4-bearing plasma cell infiltration in pancreatic tissues affected by AIP, and systemic other organ involvements in AIP with similar IgG4-bearing plasma cell features opened the gateway from AIP to IgG4-RD. The systemic distribution of IgG4-RD seems to be capable of affecting every organ, causing well-established members including AIP, lacrimal and salivary gland lesions such as Mikulicz\'s disease, respiratory diseases, sclerosing cholangitis, kidney diseases, and retroperitoneal fibrosis. IgG4-RD has been diagnosed worldwide, and international collaboration efforts on the disease have led to consensus publications on its nomenclature, pathology findings, and management approach. The algorithms developed for the comprehensive diagnostic criteria for IgG4-RD have remarkably increased detection sensitivity. Oral glucocorticoids are the first-line agents for remission induction, and certain patients with high disease activity may benefit from maintenance therapy afterwards. Originally, IgG4-RD had been considered reversible and to have a good prognosis; however, long-term afflictions sometimes result in transition to advanced-stage conditions with dysfunction and/or complicating malignancy. The immunological abnormalities in IgG4-RD have been reported in both innate and adaptive immune systems; however, it remains unclear whether IgG4 has a pathogenic role or a protective one in disease onset and progression.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz\'s disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.

According to a new concept for the classification and division of autoimmune diseases, Mikulicz\'s disease and Küttner\'s tumor belong to immunoglobulin G4-related diseases (IgG4-RD) and fulfil their diagnostic criteria. The aim of this study was to summarize the new classification concepts of IgG4-RD in the head and neck area and to review their clinical, histopathological and serologic criteria and the methods used in the diagnostic workup with respect to their advantages, limitations and differentiative value. The PubMed, Web of Science, Google Scholar, and Scopus databases were searched for articles published between 2009 and 2019 using the following key words: IgG4-related diseases, Mikulicz\'s disease, Küttner\'s tumor, salivary glands, xerostomia. Results of the review of the literature revealed that Mikulicz\'s disease and Küttner\'s tumor fulfil the same diagnostic criteria but may manifest different clinical symptoms which determine the choice of the different diagnostic tools.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz\'s disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.

BACKGROUND: We present a case of Mikulicz\'s Disease with hypophysitis. This is a rare clinical association as part of the group of IgG4- related diseases, a group of disorders which can have multiorgan involvement.
METHODS: A 55-year-old male patient was diagnosed with Mikulicz\'s disease. He was treated with oral steroids for six months with complete resolution. After two years the patient presented with fatigue, generalised weakness, and weight loss of 11 kg over six months. On evaluation he was found to have panhypopituitarism. MRI pituitary revealed homogeneously enlarged, well enhancing pituitary with thickening of the stalk. Serum IgG4 levels were significantly elevated. The patient was treated with methyl prednisolone pulse therapy followed by oral steroids for three months. He developed diabetes insipidus after starting steroid therapy. There was a significant resolution in the enlargement of the pituitary and stalk thickening at three months.
RESULTS: The clinical, biochemical, and radiological findings of hypophysitis associated with Mikulicz\'s disease are presented with a brief review of literature.
CONCLUSIONS: IgG4-related diseases are rare and have recently been recognised as a cause of hypophysitis. They can have multiorgan involvement. A high index of suspicion is required for clinching this rare diagnosis, which can be confirmed by measurement of serum levels of IgG4. Steroid therapy can reverse the inflammatory changes in IgG4 hypophysitis. (Endokrynol Pol 2016; 67 (6): 622-626).

OBJECTIVE: To characterize the clinical features of IgG4-related disease (IgG4-RD) in China.
METHODS: A prospective cohort study of IgG4-RD was carried out in Peking Union Medical College Hospital between 2011 and 2013. Patients with newly diagnosed IgG4-RD were enrolled.
RESULTS: A total of 118 patients with IgG4-RD were enrolled, including 82 males and 36 females, aged 53.1 (s.d. 13.6) years. The most common symptom at onset was lacrimal gland swelling (38/32.2%). A range of organs were involved: 77 patients (65.3%) had lymphadenopathy, 76 (64.4%) had sialadenitis, 60 (50.8%) had dacryoadenitis, 45 (38.1%) had autoimmune pancreatitis, 32 (27.1%) had pulmonary involvement, 31 (26.3%) had periaortitis/retroperitoneal fibrosis, 29 (35.4% of male patients) had prostatitis and 29 (24.6%) had renal involvement. In addition, there were 21 (17.8%) cases of sclerosing cholangitis, 15 (12.7%) of sinusitis and 10 (8.5%) of inflammatory pseudotumour. Uncommon manifestations included mediastinal fibrosis, skin involvement, sclerosing thyroiditis, hypophysitis, orchitis and colitis. Multiple organ involvement was observed in 93 patients, whereas only 4.2% had only a single organ involved. A history of allergy was reported in 73 (61.9%) patients. The serum IgG4 level was elevated in 97.5% and was correlated with the number of organs involved. Most patients were treated with glucocorticoids alone or in combination with immunosuppressive drugs, and the majority usually improved within 3 months.
CONCLUSIONS: IgG4-RD is a systemic inflammatory and sclerosing disease. Parotid and lacrimal involvement (formerly called Mikulicz\'s disease), lymphadenopathy and pancreatitis are the most common manifestations. Patients with IgG4-RD showed favourable responses to treatment with glucocorticoids and immunosuppressive agents.

Although considered essential for diagnosing IgG4-related disease (IgG4-RD), biopsy of target organs is often difficult to perform. Such was the case of a 56-year-old man admitted with general malaise and weight loss. Computed tomography revealed swelling of the submandibular gland, mild dilatation of the main pancreatic duct, renal involvement, periaortitis, and swelling of the lymph nodes in the abdominal cavity. Laboratory testing revealed elevated serum IgG4 level. These findings were suggestive of IgG4-RD; however, the patient refused consent for biopsy of the target organs for a definitive diagnosis for the invasiveness. Therefore, we tried to perform a biopsy from minor salivary gland, which revealed no sign of clinical abnormality because the biopsy is not an invasive diagnostic procedure. As a result, the biopsy revealed significant IgG4-positive plasma cell infiltration, allowing for definitive IgG4-RD diagnosis. Administration of oral prednisolone (30 mg/day) effectively improved all symptoms. These findings indicate that minor salivary gland biopsy is an effective means of IgG4-RD diagnosis in patients for whom biopsy of target organs is difficult even if there were no sign of clinical abnormality in appearance.

OBJECTIVE: Inducting clinical remission by glucocorticoid treatment is relatively easy in IgG4-related disease (IgG4-RD), but relapse also occurs easily with tapering of the steroid dose. The present study tried to analyse the cases to extract predictors of relapse present at the diagnosis of IgG4-RD.
METHODS: Subjects comprised 79 patients with IgG4-related dacryoadenitis and sialadenitis, known as Mikulicz\'s disease, who were diagnosed between April 1997 and October 2013 and followed-up for >2 years from the initial induction treatment. They were applied to Cox proportional hazard modelling, based on the outcome of interval to relapse. We performed multivariate analysis for the clinical factors of these cases and identified predictors of relapse.
RESULTS: Identified factors were male sex and younger onset in cases without organ involvement at diagnosis and low levels of serum IgG4 in cases with organ dysfunction at diagnosis. Complication with autoimmune pancreatitis and low steroid dose at initial treatment also tended to be associated with recurrence.
CONCLUSIONS: Follow-up is important in cases with recognized risk factors for relapse, including male sex and younger onset in cases without organ damage.