Mikulicz’s disease combined with IgG4-related hypophysitis: a case report – BMC Geriatrics

IgG4-RD is a rare, systemic, immune-mediated disease first identified in elderly Japanese men at the beginning of the 21st century [10], and the disease was officially named in 2010 [11]. Antigen presentation by B cells, induction of differentiation by Th2 cell-dominant B cells, and the pathogenic role of CD 4 + CTL in ultimately causing tissue fibrosis are the possible mechanisms of IgG4-RD [12,13,14,15]。.

The clinical manifestations of IgG4-RD show gender disparities, and Wang et al. [16] discovered significant gender differences in the affected organs in patients aged ≥ 55 years old, with superficial organ involvement (e.g., MD and thyroiditis) being more common in female patients and visceral organ involvement (autoimmune pancreatitis, sclerosing cholangitis, and retroperitoneal fibrosis) being more common in male patients. IgG4-RD rarely affects a single organ, and about 58-88% of patients have multiple organ involvement. When the pituitary gland is involved, it usually presents as pituitary inflammation. The clinical manifestations of IgG4-RH vary depending on the site of involvement. Symptoms associated with hypopituitarism (e.g., vomiting, nausea, weight loss, fever, loss of appetite, and loss of libido) may be seen when the anterior lobe of the pituitary gland is involved. Involvement of the posterior lobe of the pituitary gland can lead to urolithiasis [5]. Moreover, a thickened pituitary stalk and pituitary gland can compress the optic nerve or optic chiasma, resulting in decreased visual acuity, altered color vision, and visual field defects, which can occur independently or simultaneously with other organ involvements [17].The diagnosis of IgG4-RD should be based on a combination of typical histopathological features, clinical signs and symptoms, serological findings, and imaging manifestations.

In 2019, with the support of the American College of Rheumatology and the European Union of Rheumatology, a global panel of experts in IgG4-RD developed a comprehensive classification system [1]. Involvement of multiple glands account for a large proportion of this classification system. Both SS and MD may present with marked enlargement of the parotid, submandibular, and lacrimal glands. In 1953, Morgan et al. [18] reported that MD and SS were pathologically identical and considered a subtype of SS. However, further research by Yamamoto et al. [19] revealed that MD showed high serum IgG4 levels and IgG4 + plasma cell infiltration in the lacrimal and salivary gland tissues, whereas SS did not have these pathological findings, suggesting that the two are different diseases. SS and MD are differentiated based on their typical histopathology, laboratory tests, and clinical features. MD is usually characterized by bilateral, symmetrical, and painless swelling, and unlike SS, symptoms such as dry mouth, dry eyes, or arthralgia are rare. In our case, the symptoms of dry mouth and dry eyes were not obvious, which was different from that of SS, the serological IgG4 was elevated, and the histopathology of mandible suggested that the plasma cell infiltration of IgG4 + supported the diagnosis of MD. The change of pituitary gland is an important criterion in the diagnostic criteria of IgG4-RH. The elderly patient mainly presents with pituitary morphological abnormalities characterized by thickened of the pituitary stalk, which raises suspicion of a malignant tumor. However, previous studies have indicated that pituitary stalk thickness with loss of posterior MRI signal cannot differentiate whether metastatic lesions are caused by systemic diseases [20]. Linking clinical characteristics with the absence of systemic clinical and biological signs help discern whether a pituitary lesion needs more thorough workup to rule out metastasis from a distant primary [21]. The patient presents no clinical symptoms of malignant tumors and both whole-body CT and serological examinations show no evidence of tumors. Gutenber et al. [22]developed a clinic-radiological scoring system that can effectively differentiate between pituitary inflammation and pituitary adenoma. The patient scored − 4 in the system, indicating a diagnosis of pituitary inflammation.

Currently, glucocorticoids (GCs) remain the first-line treatment for IgG4-RD. In our cases, prednisone 30 mg/d was administered. After 2 months, We observed the reduction of the mass and the disappearance of symptoms such as nausea and vomiting, indicating that glucocorticoid therapy may effective for this patient. However, for patients with high disease activity or a high risk of relapse, a tapering of GCs is recommended, followed by maintenance therapy with disease-modifying antirheumatic drugs (DMARDs). Predictors of relapse after treatment can include baseline plasma cell counts in serum, serum IgG4 levels at initial treatment, serum IgG4 levels in response to treatment, and the results of 18 F-FDG PET/CT scans. Initial serum IgG4 levels are primarily used to predict the risk of relapse after treatment with DMARDs, whereas changes in serum IgG4 levels in response to treatment can be evaluated in terms of the risk of relapse when treated with GCs alone or in combination with DMARDs [23,24,25,26]. The diagnosis of the patient in the current case was confirmed by the improvement of clinical symptoms, serologic IgG4 levels, and imaging manifestations after treatment with GCs, compared to pretreatment status. For patients who experience relapse, a combination therapy with DMARDs is recommended. Some studies have found that the combination of GCs with low-dose rituximab is more effective and safer in the treatment of IgG4-RD compared to a combination of GCs and leflunomide [27]. Rituximab has also been found to be important in the remission of IgG4-RD and in maintaining its stability. However, the treatment has some economic limitations [28];therefore, a multifaceted assessment is needed when choosing a treatment regimen.

In summary, we report an elderly female patient with Mikulicz’s disease complicated with IgG4-associated hypophysitis. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.