A case of acute bilateral iodine-induced submandibular sialadenitis: Ultrasound findings.

Acute sialadenitis is a rare adverse reaction to iodine-based contrast agents. Ultrasound (US) is usually the preferred imaging method to evaluate the salivary glands; along with clinical and anamnestic data, US allows the diagnosis of contrast-induced sialadenitis. We present a case of acute bilateral submandibular sialadenitis induced by intravenous administration of iodine-based contrast media for a contrast-enhanced computed tomography scan diagnosed by US.

A Mouse Model for Dietary Xenosialitis: ANTIBODIES TO XENOGLYCAN CAN REDUCE FERTILITY.

Humans can incorporate the xenoglycan N-glycolylneuraminic acid (Neu5Gc) from the diet into reproductive tissues and secretions. Most humans also have circulating antibodies specific for this dietary xenoglycan. The potential for inflammation induced by incorporated Neu5Gc and circulating anti-Neu5Gc antibodies, termed xenosialitis, has been discussed as a factor influencing several human diseases. Potential effects of xenosialitis on human fertility remain unknown. Here, we investigate possible adverse effects of the presence of Neu5Gc on sperm or endometrium combined with anti-Neu5Gc antibodies in semen or uterine secretions in a mouse model. We use Cmah(-/-) mice, humanized for Neu5Gc deficiency. We find that the viability, migration, and capacitation of sperm with incorporated Neu5Gc are negatively affected when these are exposed to anti-Neu5Gc antibodies. In addition, we find that after copulation, activated uterine neutrophils and macrophages show increased phagocytosis of sperm in the presence of anti-Neu5Gc antibodies via the complement receptor 3 (C3R) and Fcγ I/II/III (Fc receptor). Furthermore, Neu5Gc in endometrial cells combined with the presence of anti-Neu5Gc antibodies alters the receptivity and decidualization of endometrial explants. These studies provide mechanistic insights on how Neu5Gc on sperm and/or endometrium combined with anti-Neu5Gc antibodies in semen and uterine fluid might contribute to unexplained human infertility.

RORγt antagonist suppresses M3 muscarinic acetylcholine receptor-induced Sjögren's syndrome-like sialadenitis.

We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3+ T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R-/- ) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1-/- ) mice (M3R-/- →Rag-1-/- ) with MIS. Immunized M3R-/- mice (pretransfer treatment) and M3R-/- →Rag-1-/- mice (post-transfer treatment) were treated with A213 every 3 days. Salivary volume, severity of sialadenitis and cytokine production from M3R peptide-stimulated splenocytes and lymph node cells were examined. Effects of A213 on cytokine production were analysed by enzyme-linked immunosorbent assay (ELISA) and on T helper type 1 (Th1), Th17 and Th2 differentiation from CD4+ T cells by flow cytometry. Pretransfer A213 treatment maintained salivary volume, improved MIS and reduced interferon (IFN)-γ and interleukin (IL)-17 production significantly compared with phosphate-buffered saline (PBS) (P < 0·05). These suppressive effects involved CD4+ T cells rather than CD11c+ cells. Post-transfer treatment with A213 increased salivary volume (P < 0·05), suppressed MIS (P < 0·005) and reduced IFN-γ and IL-17 production (P < 0·05). In vitro, A213 suppressed IFN-γ and IL-17 production from M3R-stimulated splenocytes and CD4+ T cells of immunized M3R-/- mice (P < 0·05). In contrast with M3R specific responses, A213 suppressed only IL-17 production from Th17 differentiated CD4+ T cells without any effect on Th1 and Th2 differentiation in vitro. Our findings suggested that RORγt antagonism is potentially suitable treatment strategy for SS-like sialadenitis through suppression of IL-17 and IFN-γ production by M3R-specific T cells.

Flagellar filament structural protein induces Sjögren's syndrome-like sialadenitis in mice.

OBJECTIVE: Sjögren's syndrome (SS) is a systemic autoimmune disease that primarily affects lacrimal and salivary glands. We previously reported that FliC derived from Escherichia coli could induce autoimmune pancreatitis-like lesions. From these results, we speculated that FliC could also induce SS-like exocrinopathy. In this study, we investigated the effects of chronic exposure to FliC on lacrimal and salivary glands and the possibility that it might lead to an autoimmune response. METHODS: C57BL/6 mice were repeatedly injected with FliC and histological changes, serum levels of cytokine/chemokines and autoantibodies were evaluated at different time points after the final injection. The presence of sialadenitis was diagnosed by histological methods. RESULTS: In FliC-treated groups, 57% of subjects developed inflammatory cell infiltrates around ducts in mandibular salivary glands, but not lacrimal glands. In addition, serum levels of total IgG, IgG1, and IgG2a were significantly higher in FliC-treated groups. Intriguingly, serum anti-SSA/Ro levels were also significantly higher in FliC-treated groups. Cytokine analysis revealed that serum levels of IL-1ß, IL-12p70, IL-13, IFN-γ, IL-15, and IL-23 seemed to be higher in FliC-treated mice. CONCLUSIONS: Our data suggest that FliC-treated mice develop an SS-like phenotype. Our model may elucidate the relationship between commensal bacteria and SS.

Iodide Mumps Complicating Coronary and Carotid Angiography.

We report a case of asceptic sialadenitis that occurred in a patient with end-stage renal failure following administration of iodinated contrast for coronary and carotid angiography. This is a rare but important complication of iodinated contrast. Early diagnosis of iodide mumps following angiography avoids unnecessary investigations and treatment. In this case the patient underwent haemodialysis with subsequent complete resolution of the sialadenitis, a treatment that has previously not been reported for this condition.

A review and assessment of drug-induced parotitis.

OBJECTIVE: To review the current literature on drug-induced parotitis. DATA SOURCES: Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality. DATA SYNTHESIS: Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports. CONCLUSIONS: Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include l-asparaginase, clozapine, and phenylbutazone. Many other drugs have been implicated in the development of parotitis; however, the evidence supporting this association is insufficient to determine causality at this time.

Differences between radioactive iodine-induced sialadenitis and chronic obstructive parotitis.

The purpose of this study was to clarify the differences in the diagnosis and treatment outcomes between radioactive iodine-induced sialadenitis (RAIS) and chronic obstructive parotitis (COP). The study cohort comprised 47 consecutive patients diagnosed with RAIS and 50 patients with COP. All patients were treated by interventional endoscopy. Clinical, sialography, and endoscopy characteristics and treatment outcomes were compared between the two groups. Compared with the COP group, the RAIS group included more females (male:female ratio 1:8.4 vs 1:2.1; P = 0.011) and had a younger onset age (42 vs 50 years; P = 0.001) and shorter disease duration prior to hospital visit (5.4 vs 34.8 months; P < 0.001). In the RAIS group, sialography revealed obliteration of the main duct (20.4% vs 0%; P < 0.001), non-visualization of the main gland (23.7% vs 0%; P < 0.001), and incomplete contrast filling of the main gland (19.4% vs 6.4%; P = 0.008), which were scarcely observed in the COP group. Endoscopy revealed a higher percentage of duct atresia in RAIS compared to COP (20.4% vs 0%; P < 0.001). During follow-up, a higher percentage of RAIS patients had duct atresia and gland atrophy (49.5% vs 1.1%, P < 0.001). Compared with COP, RAIS more commonly involves younger females and has a shorter disease duration. Atresia of the main duct and atrophy of the gland parenchyma occur more often despite the use of interventional endoscopy.

[Acute sialadenitis by iodine contrast medium administration].

Acute iodide sialadenitis is a rare adverse reaction to iodinated contrast that causes self-limited salivary gland swell-ing. Its pathogenesis is still unclear, although kidney failure may be a risk factor. The diagnosis is initially clinical but angioedema, infections and lithiasis should be included in the differential diagnosis. No treatment or prophylaxis was proven to be beneficial. Although its prognosis is benign, associated complications have been reported. We report a case of 68-year-old man with swelling of the submandibular salivary glands after the administration of iodine-based contrast media during an abdominal computed tomography examination. Because of the widespread use of iodinated contrast enhanced imaging and interventional techniques, clinicians should be aware of this issue.

Inducible nitric oxide synthase increases secretion from inflamed salivary glands.

OBJECTIVE: Salivary gland secretion is dependent on cholinergic stimulation via autonomic nerves and calcium signalling in acinar cells. Secretory dysfunction associated with SS may be partly caused by the damaging effects of increased glandular concentrations of nitric oxide (NO) derived from up-regulation of inducible NO synthase (iNOS) that accompanies glandular inflammation. The present study examines the effects of increased iNOS expression on salivary gland secretory function. METHODS: The inflammogen lipopolysaccharide (LPS) was introduced intraductally into rat submandibular glands, and glandular responsiveness to cholinergic stimulation was determined. RESULTS: LPS provoked a rapid, long-lasting inflammation, increasing gland weight (by almost 20%) and inflammatory cell infiltration at 3 and 24 h. Immunoblotting of glandular homogenates indicated that iNOS expression was increased approximately 4-fold, and immunohistochemistry of frozen tissue sections showed increased iNOS expression in acinar cells. Salivary secretion from inflamed glands was significantly increased in response to low doses of methacholine and accompanied by increased acinar cell calcium signalling in vitro. Prior administration of the iNOS inhibitors, aminoguanidine or L-NIL [L-N6-(1-iminoethyl)-lysine dihydrochloride] abolished increased secretion and acinar cell calcium signalling. CONCLUSIONS: Up-regulation of glandular iNOS expression can increase cholinergically evoked salivary secretion and appears to offset any secretory hypofunction linked with glandular inflammation. It seems unlikely that increased glandular levels of NO are responsible for the secretory hypofunction that accompanies SS.

Incidence and risk factors for radioactive iodine-induced sialadenitis.

BACKGROUND: Radioactive iodine (131I) is one of the treatments of hyperthyroidism and differentiated thyroid carcinoma (DTC). Swelling of salivary glands are one of the possible side effects of this treatment, known as radioactive iodine-induced sialadenitis (RAIS). The prevalence of RAIS varies widely and no specific risk ratio has been established. OBJECTIVES: To determine the incidence of RAIS, analysing the epidemiological data and tumour- and treatment-related factors that may influence the development of the disease. MATERIAL AND METHODS: 197 patients who received radioiodine treatment between 2015 and 2017 were studied (76.6% women). The variables studied were age, gender, weight, height, and body mass index; presence of high blood pressure, dyslipidemia, diabetes, and thyroid diseases; cumulative radioiodine dose, presence of sialadenitis, affected salivary gland, and the time of onset. RESULTS: 14 patients developed sialadenitis (78.6% women), all with DTC. The incidence of sialadenitis was 3.4% overall and 6.3% among DTC patients. Furthermore, we found that higher cumulative radioiodine doses confer a greater risk of developing sialadenitis, with a hazard ratio of 1.009 (p = .001). No association was found between the epidemiologic data studied and sialadenitis. CONCLUSIONS: In this series, a dose-dependent relationship was found between radioiodine treatment and sialadenitis.

Characterization of Iodide-induced Sialadenitis: Meta-analysis of the Published Case Reports in the Medical Literature.

PURPOSE: To evaluate the patient presentation of postcontrast sialadenitis and factors associated with its duration of symptoms through meta-analysis of case reports. BACKGROUND: Acute iodide sialadenitis, or "iodide mumps," is a rare adverse reaction to iodinated contrast causing salivary gland swelling. The condition may be underdiagnosed, with researchers postulating that its true incidence may be close to 1-2%. METHODS AND MATERIALS: This study was a meta-analysis performed using PRISMA Reporting Standards. A literature search with no language restriction was performed of the Medline database, primarily through PubMed, using keywords: "iodide mumps," "iodide sialadenitis," "sialadenitis," "salivary enlargement," "contrast reaction," "parotid swelling," and "submandibular swelling." Matching case reports and case series were reviewed, and data regarding the subjects' demographics, renal function, contrast administration, and symptoms were extracted. Uni- and multivariate linear regression analyses were applied to assess the predicting factors of a prolonged symptoms duration. RESULTS: Sixty-five case reports and case series were identified, with 77 cases of iodide-induced sialadenitis. Two cases were unpublished and from the author's institution. Reported subjects' median age was 63 years, and 61% (47/77) were males. Median time to onset was 16 hours, and symptoms resolved in a median of 3 days after the initial onset. Twenty-seven subjects (35%, 27/77) were reported to have an impaired renal function at baseline. Administration of nonionic, low osmolarity contrast medium was reported most frequently (53%, 41/77). There was no difference in resolution of symptoms among subjects with impaired versus normal renal function. Symptoms were resolved in all cases over a median of 3 days with no statistically significant difference between those who received therapeutic intervention and those who did not (p = 0.430). Older age and longer time to onset were significantly associated with longer duration of symptoms in both uni- and multivariate linear regression models, and presence of tenderness demonstrated statistical significance associated with longer duration of symptoms in the univariate model. CONCLUSION: Postcontrast sialadenitis is a rare reaction to iodinated contrast media. Older age and a longer time to onset of symptoms are associated with longer duration of symptoms.

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS). DESIGN: Longitudinal cohort study. SUBJECTS AND METHODS: A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands. MAIN OUTCOME MEASURES: Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no). RESULTS: Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non-PI based HAART. CONCLUSIONS: PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.