Postoperative Acute Submandibular Sialadenitis: A Case Report.

Acute postoperative sialadenitis is a rare complication usually after surgery involving extreme head and neck rotation, such as posterior fossa surgery. It is characterized by the development of swelling in the submandibular region, usually contralateral to the surgical side, either immediately or within hours post-operatively. We report a case of a 43-year-old woman who developed sialadenitis leading to upper airway obstruction in the postoperative period. Further, she developed bilateral neck and face swelling. Dexmedetomidine used as an infusion throughout the surgery could be an additional cause. Swelling without signs of inflammation is rapidly progressive and may cause airway obstruction. Therefore, awareness and recognition are important, as a delay in airway securement can cause a complete collapse of the airway. Keywords: airway obstruction; case reports; sialadenitis.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Central Diabetes Insipidus Due to IgG4-related Hypophysitis That Required over One Year to Reach the Final Diagnosis Due to Symptoms Being Masked by Sialadenitis.

Pituitary inflammation due to IgG4-related disease is a rare condition and is sometimes accompanied by central diabetes insipidus. Central diabetes insipidus produces a strong thirst sensation, which may be difficult to distinguish when complicated by salivary insufficiency. A 45-year-old man was admitted to our department for a thorough examination of his thirst and polyuria. He had suddenly developed these symptoms more than one year earlier and visited an oral surgeon. Swelling of the left submandibular gland, right parotid gland, and cervical lymph nodes had been observed. Since his IgG4 level was relatively high at 792 mg/dL and a lip biopsy showed high plasmacytoid infiltration around the gland ducts, he had been diagnosed with IgG4-related disease. He had started taking 0.4 mg/kg/day of prednisolone, and his chief complaint temporarily improved. However, since the symptom recurred, he was referred to our institution. After admission, to examine the cause of his thirst and polyuria, we performed a water restriction test, vasopressin loading test, hypertonic saline loading test and pituitary magnetic resonance imaging. Based on the findings, we diagnosed him with central diabetes insipidus due to IgG4-related hypophysitis. We increased the dose of prednisolone to 0.6 mg/kg/day and started 10 µg/day of intranasal desmopressin. His symptoms were subsequently alleviated, and his serum IgG4 level finally normalized. We should remember that IgG4-related disease can be accompanied by hypophysitis and that central diabetes insipidus is brought about by IgG4-related hypophysitis. This case report should remind physicians of the fact that pituitary inflammation due to IgG4-related disease is very rare and can be masked by symptoms due to salivary gland inflammation, which can lead to pitfalls in the diagnosis in clinical practice.

Usual Interstitial Pneumonia Pattern Interstitial Lung Disease Developed in a Patient with IgG4-related Chronic Sclerosing Sialadenitis.

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.

Focal lymphocytic sialadenitis and ectopic germinal centers in oral reactive lesions and primary Sjögren's syndrome: a comparative study.

Focal lymphocytic sialadenitis (FLS), an important diagnostic criterion for Sjögren's syndrome (SS) diagnosis, can also be observed when assessing minor salivary gland (mSG) biopsies from healthy asymptomatic individuals (non-SS patients). Fifty cases of primary SS (pSS group) and 31 cases of oral reactive lesions (non-SS non-sicca group) containing also typical FLS features, were assessed by morphological and immunohistochemical (CD10, CD23 and Bcl-6) analysis, aiming at the detection of GCs. All pSS cases showed FLS with focus score (FS) ≥ 1. In the non-SS non-sicca group, 12, 10 and 9 cases showed FLS with FS ≥ 1, FLS with FS < 1 and FLS associated with chronic sclerosing sialadenitis with FS < 1, respectively. The morphological analysis revealed similar frequency of GCs in pSS (20%) and non-SS non-sicca group (19%). The area (p = 0.052) and largest diameter (p = 0.245) of GCs were higher in pSS than non-SS non-sicca group. The FS and number of foci were significantly higher in pSS than non-SS non-sicca group with FS < 1. Immunohistochemistry confirmed all morphological findings (GCs showing CD23 and Bcl-6 positivity, with variable CD10 expression) and additionally in 3 and 1 cases of the pSS and non-SS non-sicca group, respectively. Moreover, another 6 and 2 cases of the pSS and non-SS non-sicca group with FS ≥ 1, respectively, showed positivity only for CD23. FLS can also be observed when assessing oral reactive lesions, which showed similar frequency of GCs with those found in pSS patients. Further studies, including functional analysis of lymphocytic populations and GCs in FLS, are encouraged.

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

Identifying sialoliths through SEM technology.

OBJECTIVE: To define SEM characteristics that may aid identification of sialoliths. MATERIALS: Two sialoliths from modern patients affected by sialadenitis. METHODS: Samples were coated with silver and subjected to scanning electron microscopy using an energy-dispersive X-ray spectroscopy detector. Samples were then sectioned to permit study of the internal structure. RESULTS: Sialoliths show an external smooth surface with no distinctive features. Internal structures consist of a distinctive aggregate of coarse granules of different sizes surrounded by a lamellar coat. Elemental composition consists of carbon, phosphate, calcium and oxygen, with traces of magnesium. The proportion of these elements differs between the core and the surface. CONCLUSION: Although elemental composition is not specific, SEM analyses of sialoliths greatly differ from those of sesamoid bones, gallstones and nephroliths. Therefore, SEM analysis constitutes a useful tool for the precise identification of small calcified structures recovered during archaeological excavations. SIGNIFICANCE: Precise identification of calcified structures may provide information about nutritional and/or pathological aspects of past individuals. LIMITATIONS: Sialoliths are less common than other types of calcifications, and only two cases were analyzed in this study. FUTURE PROSPECTS: SEM technology should be applied to identify the etiology of all minute calcified remains recovered during archaeological excavations of burial sites.

Dysbiotic oral microbiota and infected salivary glands in Sjögren's syndrome.

Key events in the pathogenesis of SjÓ§gren syndrome (SS) include the change of salivary gland epithelial cells into antigen-presenting cell-like phenotypes and focal lymphocytic sialadenitis (FLS). However, what triggers these features in SS is unknown. Dysbiosis of the gut and oral microbiomes is a potential environmental factor in SS, but its connection to the etiopathogenesis of SS remains unclear. This study aimed to characterize the oral microbiota in SS and to investigate its potential role in the pathogenesis of SS. Oral bacterial communities were collected by whole mouthwash from control subjects (14 without oral dryness and 11 with dryness) and primary SS patients (8 without oral dryness and 17 with dryness) and were analyzed by pyrosequencing. The SS oral microbiota was characterized by an increased bacterial load and Shannon diversity. Through comparisons of control and SS in combined samples and then separately in non-dry and dry conditions, SS-associated taxa independent of dryness were identified. Three SS-associated species and 2 control species were selected and used to challenge human submandibular gland tumor (HSG) cells. Among the selected SS-associated bacterial species, Prevotella melaninogenica uniquely upregulated the expression of MHC molecules, CD80, and IFNλ in HSG cells. Concomitantly, P. melaninogenica efficiently invaded HSG cells. Sections of labial salivary gland (LSG) biopsies from 8 non-SS subjects and 15 SS patients were subjected to in situ hybridization using universal and P. melaninogenica-specific probes. Ductal cells and the areas of infiltration were heavily infected with bacteria in the LSGs with FLS. Collectively, dysbiotic oral microbiota may initiate the deregulation of SGECs and the IFN signature through bacterial invasion into ductal cells. These findings may provide new insights into the etiopathogenesis of SS.

Xanthogranulomatous Sialadenitis, an Uncommon Reactive Change is Often Associated with Warthin's Tumor.

Xanthogranulomatous sialadenitis (XGS) is rare in salivary glands and only reported in the literature as single cases. Here we report a cohort of four cases with XGS and summarize the clinicopathologic features of these cases. All four patients had persistent mass lesions concerning for neoplasm. In two patients (patient 1 and 3), the initial fine needle aspirations (FNAs) contained oncocytic cells consistent with or suspicious for Warthin's tumor, but follow-up FNAs showed only inflammation and/or debris indicating tumor infarction after FNA. All patients eventually had surgical resection. Histologically, all cases contained abundant macrophages with necrosis and fibroblastic proliferation. Warthin's tumor with a grossly identifiable tumor nodule (0.7 cm) was noted in patient 1 and a microscopic focus (0.2 cm) of Warthin's tumor was identified in patient 3. No identifiable tumor was observed in patient 2 and 4. There are a total of 10 XGS cases in the literature (including four from this series) and Warthin tumor was identified in 50% of reported cases of XGS, suggesting that XGS is an uncommon reactive process to spontaneous or procedure-induced infarction of Warthin tumor. As a diagnostic mimicker for malignancy, a thorough examination and generous sampling of surgical resection specimen is warranted, although a benign salivary gland neoplasm, commonly Warthin's tumor, is often identified.

Parapharyngeal abscess and vocal cord palsy caused by minor salivary gland sialadenitis: an atypical presentation treated using an endoscopic surgical approach.

Parapharyngeal infections carry a significant risk of extensive suppuration and airway compromise. We report the case of a patient presenting with a right paranasopharyngeal abscess, featuring atypical symptoms that made diagnosis particularly challenging. Complications included evidence of right vocal cord paralysis, likely secondary to involvement of the vagus nerve. Notably, this paralysis occurred in isolation, without involvement of cranial nerves IX or XI, which would be expected from jugular foramen encroachment. Imaging demonstrated the presence of a collection extending towards the skull base, which was drained using a transnasal endoscopic approach, avoiding the use of external incisions. Tissue biopsies from the abscess wall suggest that the underlying aetiology was minor salivary gland sialadenitis, which has not been previously reported in the literature.

Hyperglycemia and Salivary Gland Dysfunction in the Non-obese Diabetic Mouse: Caveats for Preclinical Studies in Sjögren's Syndrome.

The Non-obese Diabetic (NOD) mouse model for type I diabetes also develops some features of Sjögren's syndrome (SS). Since the source of the mice and the environment exert a strong influence on diabetes, this study investigated SS development in NOD mice obtained from two vendors. Female NOD mice from The Jackson Laboratory (JAX) and Taconic Biosciences were monitored for blood glucose and pilocarpine-induced salivation. The gut microbiome was analyzed by 16S rRNA sequencing of stool DNA. At euthanasia, serum cytokines and sialoadenitis severity were evaluated. The onset of diabetes was significantly accelerated in JAX mice compared to Taconic mice. Although the gut microbiome between the two groups was distinct, both groups developed sialoadenitis. There was no correlation between the severity of sialoadenitis and reduced saliva production. Instead, salivary gland dysfunction was associated with hyperglycemia and elevation of serum IL1ß, IL16, and CXCL13. Our data suggest that inflammatory pathways linked with hyperglycemia are confounding factors for salivary gland dysfunction in female NOD mice, and might not be representative of the mechanisms operative in SS patients. Considering that NOD mice have been used to test numerous experimental therapies for SS, caution needs to be exerted before advancing these therapeutics for human trials.

IgG4-related sialadenitis complicated with type III mixed cryoglobulinemia: A case report.

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.

Impact of sclerosing dacryoadenitis/sialadenitis on relapse during steroid therapy in patients with type 1 autoimmune pancreatitis.

OBJECTIVES: Steroids are the first-line drugs for induction of remission in patients with type 1 autoimmune pancreatitis (AIP), and the usefulness of steroid maintenance therapy to prevent relapse has recently been reported. However, even during steroid therapy, a relatively large percentage of patients relapse and the predictive factors for relapse have not yet been elucidated. The aim of this study was to clarify the predictive factors for relapse of AIP patients during steroid therapy. MATERIALS AND METHODS: The medical records of 76 patients with type 1 AIP with continued steroid therapy after induction of remission were analyzed retrospectively. The relapse rate during steroid therapy was evaluated, and the risk factors for relapse were investigated by univariate and multivariate analysis of clinical factors. RESULTS: Relapse occurred in 28.9% (22/76) of the patients. The cumulative relapse rates were 10.5% at 1 year, 25.0% at 3 years, 34.9% at 5 years, and 43.0% at 10 years. In multivariate analysis, presence of sclerosing dacryoadenitis/sialadenitis at the time of initial diagnosis of AIP was an independent risk factor for relapse (HR 3.475, p = .009). The cumulative relapse rates of patients with sclerosing dacryoadenitis/sialadenitis reached 21.4% at 1 year, 56.0% at 3 years, and 78.0% at 5 years. CONCLUSIONS: Sclerosing dacryoadenitis/sialadenitis was a predictive factor for relapse in type 1 AIP during steroid therapy; in such cases, strict follow-up is necessary with relapse in mind.

Sialadenitis May Be Associated With an Increased Risk for Osteoradionecrosis: A Nationwide Population-Based Cohort Study.

PURPOSE: The impact of sialadenitis on osteoradionecrosis (ORN) is controversial. The aim of this study was to determine the association between sialadenitis and ORN. MATERIALS AND METHODS: Participants were derived from the Taiwanese Longitudinal Health Insurance Database. From January 1, 2000 to December 31, 2008, cases of sialadenitis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 527.2, 527.3, 527.5 to 527.7, 527.9, and 710.2) and ORN (ICD-9-CM codes 526.89, 526.5, 730.0, and 730.1) were identified. Different treatment modalities, including surgery versus medicine, were used to distinguish the severity of sialadenitis. The primary predictor variable was sialadenitis. The secondary predictor variable was severity of sialadenitis. The primary outcome variable was time to developing ORN. Other study variables were grouped for age, gender, risk factor, and medical treatment. Cox proportional hazard regression was used to investigate the associations between sialadenitis and ORN after adjusting for statistical confounders. RESULTS: The sample was composed of 47,385 patients with a mean age of 46.6 years (standard deviation, 19.9 yr) and 37.2% were men. Twenty percent had a diagnosis of sialadenitis and 1.13% had a diagnosis of ORN. Sialadenitis was associated with an increased risk of ORN (hazard ratio [HR] = 1.93; 95% confidence interval [CI], 1.61-2.31; P < .0001). After adjustment for confounders, sialadenitis was associated with ORN (multivariable HR = 1.83; 95% CI, 1.52-2.19; P < .0001). Severity of sialadenitis was associated with an increased risk of ORN; risks for ORN were 1.79 (95% CI, 1.49-2.16; P < .0001) and 3.52 (95% CI, 1.67-7.44; P < .001) in patients with mild and serious sialadenitis, respectively, compared with the no-sialadenitis cohort. For the joint effect of ORN between sialadenitis and malignancy type, patients with sialadenitis had 11.6-fold risk for ORN (95% CI, 5.58-23.9) compared with patients without malignancy. CONCLUSIONS: Sialadenitis markedly increased the risk to develop ORN. The severity of sialadenitis was positively correlated with the incidence of ORN.

Differences and similarities between IgG4-related disease with and without dacryoadenitis and sialoadenitis: clinical manifestations and treatment efficacy.

BACKGROUND: This study aimed to compare the differences and similarities in the clinical manifestations and treatment efficacy of IgG4-related disease (IgG4-RD) in patients with and without dacryoadenitis and sialoadenitis (DS). METHODS: A total of 121 untreated IgG4-RD patients in Peking Union Medical College Hospital were enrolled in this study. The patients were divided into three groups: DS-predominant (group A), non-DS (group B), and DS with other internal organs affected (group C). The patients were followed up for at least 15 months. Baseline and follow-up data were collected. The disease activity was evaluated according to the IgG4-RD responder index. RESULTS: The mean ± SD age at disease onset was 53.2 ± 14.1 years, and 71.9% of the patients were male. The prevalence of allergies was higher in groups A (21, 61.8%) and C (32, 69.6%) than group B (14, 34.1%). More patients with DS (17, 50.0%, and 17, 37.0%) had sinonasal lesions than those without DS (5, 12.2%). Moreover, an increased number of eosinophils were more common in patients with DS than in those without, as were increased serum IgG, IgG4, and IgE levels. More patients in group B and group C (28, 68.3%, and 31, 67.4%) received a combination therapy of corticosteroid and immunosuppressant. During the 15-month follow-up, 28 (23.1%) patients had disease relapse. CONCLUSION: Results demonstrated that IgG4-RD patients with DS had distinctive clinical features compared with non-DS. Allergy and sinonasal involvement were more common in patients with DS. Patients with DS showed higher serum IgG4 levels than those without DS.

The association with xerostomia from sialadenitis and the jaw osteonecrosis in head and neck cancer population: a nationwide cohort study.

OBJECTIVES: Determine the association between sialadenitis and osteonecrosis of the jaw (ONJ) in head and neck cancer (HNC) patients with varying severity of sialadenitis, treatment modalities, and cancer locations. MATERIALS AND METHODS: A total of 40,168 HNC patients, including 1907 ONJ subjects and 7559 matched comparisons, were enrolled from a Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2006. The association with sialadenitis and ONJ was estimated by logic regression and presented as the odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: The occurrence of sialadenitis increased the risk of ONJ by 2.55-fold in HNC patients (95% CI = 2.20-2.95). The ONJ incidence was proportion to sialadenitis severity (OR = 2.53 to 4.43). Irradiated HNC patients had a higher tendency to develop jaw necrosis (osteoradionecrosis, ORN) (OR = 5.05, 95% CI = 4.39-5.80). When combined with irradiation exposure, sialadenitis significantly induced the occurrence of ORN (OR = 8.94, 95% CI = 7.40-10.8), especially in oral cancer patients (OR = 15.9 95% CI = 12.5-20.3). The risk of ONJ increased with radiotherapy dosage and duration, except for nasopharyngeal cancer (NPC) patients. CONCLUSIONS: There was a close association between sialadenitis and ONJ in the HNC population. The severity of sialadenitis was positive correlated to ONJ risk. Radiotherapy combined with sialadenitis significantly raised ORN incidence in HNC patients except for NPC patients. CLINICAL RELEVANCE: HNC patients complained that xerostomia from sialadenitis might increase the risk to develop ONJ, especially among those who received radiotherapy.