Characterization of Salivary Gland Pain: A Review of the Literature / Caracterización del Dolor de Glándulas Salivales: Revisión de la Literatura

SUMMARY: The salivary glands in pathological conditions produce countless different clinical presentations, and due to their complex neuroanatomy, their pain symptoms vary widely. However, in the literature to date, few studies characterize salivary gland pain. The aim of this study was to conduct a literature review concerning the clinical characteristics of pain in various salivary gland pathologies. A literature review was done through a systematic search of scientific articles in the Web of Science (WoS), MEDLINE, Scopus, and Elton B. Stephens Company (EBSCO) databases. The free terms "salivary gland", "parotid gland", "submaxillary gland", "sublingual gland", and "pain" were used along with the Boolean operators OR and AND. The search yielded a total of 1896 articles, of which 60 fulfilled the inclusion criteria and were ultimately included in this review. It is described that pain is a nonspecific symptom of a glandular pathology and is characterized mainly by the location of the pain, which is correlated with the anatomical location of the affected salivary gland. Among the painful salivary gland pathologies, we found inflammatory disorders, including infections, obstructions, disorders secondary to hyposalivation; systemic autoimmune diseases; neoplasms, and neuropathic pain disorders. The diagnosis and management of salivary gland pain require knowledge of the causes and mechanisms of the pain, and it is to recognize the signs and symptoms of salivary gland disorders to be able to diagnose and treat them.

Las glándulas salivales en condiciones patológicas producen un sinfín de presentaciones clínicas diferentes, y debido a su compleja neuroanatomía generan variaciones en su sintomatología dolorosa. Sin embargo, en la literatura hasta ahora son escasos los estudios que caracterizan el dolor de glándulas salivales. El objetivo de este estudio fue realizar una revisión de la literatura respecto a las características clínicas del dolor en diversas patologías de glándulas salivales. Se realizó una revisión de la literatura, a través de la búsqueda sistemática de artículos científicos en las bases de datos Web of Science (WoS), MEDLINE, Scopus y Elton B. Stephens Company (EBSCO). A través de los términos libres: "salivary gland", "parotid gland", "submaxillary gland", "sublingual gland", "pain", junto con los operadores booleanos OR y AND. La búsqueda arrojó un total de 1896 artículos, de los cuales 60 cumplieron los criterios de inclusión y fueron finalmente incluidos en esta revisión. Se describe que el dolor es un síntoma poco específico para la patología glandular y está caracterizado principalmente por la localización del dolor, el cual se correlaciona con la ubicación anatómica de la glándula salival afectada. Dentro de las patologías dolorosas de glándulas salivales encontramos los trastornos inflamatorios, incluidas infecciones, obstrucciones, trastornos secundarios a hiposalivación; enfermedades sistémicas autoinmunes; neoplasias y trastornos de dolor neuropático. El diagnóstico y manejo del dolor de glándulas salivales requiere del conocimiento de las causas y mecanismos del dolor, siendo necesario reconocer los signos y síntomas de los trastornos de glándulas salivales para ser capaces de diagnosticarlos y tratarlos.

Risk factors for sialocele after parotidectomy: Does tumor size really matter?

OBJECTIVE: Sialocele that develops after parotid surgery often prolongs the treatment period and stresses both the surgeon and patient. The extent of surgery and tumor size are known to be associated with sialocele occurrence. We investigated the incidence of post-parotidectomy sialocele and the associated risk factors, with a focus on tumor size. METHODS: We retrospectively reviewed the medical records of 172 patients who underwent parotidectomy between January 2013 and May 2020 at Haeundae Paik Hospital, Inje University of Korea. We stratified patients into those with and without sialocele (fluid collection in the operative bed). We compared clinical data, patient demographics, and surgical details; we identified risk factors for sialocele development after parotid surgery. RESULTS: Seventeen patients were diagnosed with post-parotidectomy sialocele (9.88%; 17/172). Univariate logistic regression revealed that the male sex, deep lobe tumor location, and large tumor size were significantly associated with postoperative sialocele (p = 0.015, 0.009, and 0.016, respectively). We subjected these parameters to multivariate analyses; the odds ratios were 3.70, 3.58, and 2.34, respectively. Receiver operating characteristic curve analyses showed that a tumor size > 2.50 cm was the optimal cutoff in terms of predicting post-parotidectomy sialocele. CONCLUSION: Male sex, a tumor in the deep lobe, and large tumor size were strongly associated with increased risk for sialocele after parotidectomy. Tumor size > 2.50 cm serves as the cutoff identifying patients likely to experience sialocele after parotid surgery.

[Results of a nationwide survey on the treatment of salivary gland diseases in German hospitals]. / Ergebnisse einer deutschlandweiten Umfrage zur Behandlung von Speicheldrüsenerkrankungen im Krankenhaus.

BACKGROUND: Salivary gland diseases are an important part of the work of ENT physicians in hospitals. The treatment strategies depend, among other things, on the doctrine at the respective location. OBJECTIVE: The aim of this questionnaire-based study was to assess the current diagnostic workup and therapeutic strategies for salivary gland diseases in German otorhinolaryngology departments. MATERIALS AND METHODS: A survey was performed using a 25-question online questionnaire sent to all German otorhinolaryngology department directors. RESULTS: The questionnaire was answered by 92 of 175 otorhinolaryngology departments (52.6%). In the diagnosis of salivary gland tumors, a dominance of sonography and MRI was shown. Fine- and core-needle aspiration were not performed by more than 50% of the clinics. The dominant technique for parotidectomy was under microscopic control (82%). In 99% of clinics, EMG was used during resection of the parotid gland for intraoperative monitoring of the facial nerve. There was a trend towards performing partial parotidectomies (85%), lateral parotidectomies (70%), and extracapsular dissections (57%) for benign tumors of the parotid gland. The treatment concepts for malignant tumors were inconsistent. CONCLUSION: In particular, the treatment strategy and extent of surgery for benign and malignant salivary gland tumors differed depending on location. The choice of palliative (drug) therapy was also diverse. Prospective multicenter studies could help to develop evidence-based treatment strategies.

Sialography: a pictorial review.

Non-tumour inflammatory and obstructive salivary gland pathologies such as sialadenitis, sialolithiasis, sialadenosis, ductal strictures, etc. require precise radiological evaluation and mapping of salivary gland ductal system for better treatment outcome. Conventional sialography is considered as a useful and reliable technique in evaluation of salivary glands especially intrinsic and acquired abnormalities involving the ductal system and is useful for detection of non-radiopaque sialoliths which are invisible on routine plain radiographs. Primarily sialography is used as a diagnostic tool, additionally it plays an important therapeutic role as salivary gland lavage in cases of recurrent salivary gland infections and in obstructive salivary gland disorders by helping in clearance of mucous plugs or small sialoliths within the ducts. Recently, diagnostic performance of computed tomography (CT) sialography is being explored and has been reported to have high sensitivity in detection of small sialoliths and allows differentiation of sialoliths from other calcifications in glandular ductal system. Multiplanar three dimensional (3D) reconstructed CT images have been reported to play a key role in determination of anatomical location or extent of salivary gland disease without superimposition or distortion of structures. This review aims to discuss the disease specific applications of sialography and CT Sialography in particular for visualization of salivary gland disorders.

Oral mucoceles: A Brazillian Multicenter Study of 1,901 Cases.

Oral mucocele (OM) is the most common lesion of minor salivary glands. The present study aimed to report the clinical and demographic features of a large series of OMs and identify possible predictive variables associated with the recurrence rate of these lesions. A retrospective descriptive cross-sectional study was performed. A total of 43,754 biopsy records from four pathology services in Brazil were analyzed. All cases of OMs were reviewed, and clinical and demographic data were collected. The study comprised 1,002 females (56.2%) and 782 males (43.8%), with a mean age of 19.8±16.4 years (range: 01-87 years) and a 1.3:1 female-to-male ratio. The lower lip (n=1,160; 67.4%), and floor of the mouth (n=172; 10.0%), were the most common affected sites, presenting clinically as nodules (n=978; 79.4%) of smooth surface (n=428; 77.5%) and normal color (n=768, 46.7%). Excisional biopsy was the treatment in most cases (n=1,392; 78.0%). Recurrent OMs represented 6.2% of all diagnosed cases (n=117). OMs recurred more commonly in younger patients (aged<20 years) (p<0.0001), in lesions larger than 2 cm in diameter (p<0.0001), and in those located in the ventral tongue (p=0.0351). Also, recurrence rates were higher significantly in cases treated with laser surgery than in those with conventional surgery (p=0.0005). Patients with OMs should be carefully informed of its possible recurrence, especially when found on the ventral tongue of young patients.

Pediatric Salivary Gland Disease.

Salivary gland disease in the pediatric population is rare, yet it encompasses a wide spectrum of disease. It is estimated that 4.3% of salivary gland disease occurs in the pediatric population, with most classified as nonneoplastic. Further extrapolation reveals that 5% of salivary gland neoplastic diseases occur in patients younger than 20 years. Moreover, salivary gland tumors represent 1% of all head and neck tumors across all ages. Regardless, clinicians across all fields should be familiar with the workup of various pediatric salivary gland diseases and appropriate referral to a pediatric otolaryngologist.

An Update on Nontumorous Disorders of the Salivary Glands and Their Management for Internists.

Salivary disease may present as pain or swelling in unilateral or bilateral salivary glands. Symptoms may be periprandial or recurrent and inflammatory. If a patient fails conservative treatment, they should be referred to an otolaryngologist. If there is no clear cause based on history and physical examination, sialendoscopy can be performed to directly visualize tissues, provide a diagnosis, drive treatment plans, and sometimes concurrently provide therapeutic intervention. Based on the pathology visualized on sialendoscopy, treatment options include endoscopic intervention, Botox, and gland-preserving surgical techniques, which promote healing of glandular tissue, ultimately preserving function.

Salivary Gland Hypofunction and/or Xerostomia Induced by Nonsurgical Cancer Therapies: ISOO/MASCC/ASCO Guideline.

PURPOSE: To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS: Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS: A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS: For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy.Additional information can be found at www.asco.org/supportive-care-guidelines.

Bilateral multifocal nodular oncocytic hyperplasia of the parotid gland: a rare entity.

Multifocal nodular oncocytic hyperplasia is an uncommon oncocytic lesion that rarely occurs in the parotid gland. Here, we report a case of a 43-years-old woman who presented with isolated gradual swelling in the 2 parotid regions. She underwent exofacial right parotidectomy. Histologic exam confirmed the diagnosis of oncocytoma arising in a background of multifocal nodular oncocytic hyperplasia with a histological variant of clear cells. Since the lesion was diagnosed as a benign lesion, surgery of the left side was not done. Our case is characterized by: early onset, the histological variant of clear cells and the presence of synchronous oncocytoma. We describe the clinical, histological and therapeutic features of this entity.

Inner ear salivary gland choristoma extending to the middle ear with congenital profound hearing loss and facial palsy: a case report.

BACKGROUND: Salivary gland choristoma (SGCh) is a rare benign tumor reported in several unusual sites, such as the gastrointestinal tract, the optic nerve, and the internal auditory canal, but never reported in the inner ear. CASE PRESENTATION: An 8-year-old girl with a history of left profound congenital hearing loss presented to us with ipsilateral progressive severe facial nerve palsy (House-Brackmann Grade VI). The left tympanic membrane was swollen with a pulsatile tumor. Radiological investigations revealed a multilocular tumor in the inner ear extending into the middle ear and internal auditory canal (IAC). We performed a partial resection of the tumor by transmastoid approach to preserve the anatomical structure of the facial nerve. The tumor was pathologically diagnosed as SGCh. Two years after surgery, her facial function recovered to House-Brackmann Grade II and the residual tumor did not show regrowth on MRI. CONCLUSIONS: Although the natural course of this rare tumor is unknown, a partial resection is an acceptable treatment procedure when functional recovery of the facial nerve is anticipated.

A case of parapharyngeal space salivary duct cyst with fine needle biopsy suspicious for squamous cell carcinoma.

OBJECTIVES: To report a unique case of salivary duct cyst presenting as parapharyngeal space mass and review relevant literature regarding salivary duct cyst and fine needle aspiration biopsy of salivary gland lesions. METHODS: After a case description, a review of the literature regarding salivary duct cyst etiology, pathophysiology, presentation, histologic features, and the accuracy of FNA in the context of salivary gland lesions was conducted. RESULTS: Salivary duct cysts are rare, often acquired, cystic dilatations of salivary ducts thought to arise secondary to ductal obstruction, commonly occurring in the major salivary glands. Fine needle aspiration is the biopsy method of choice for most head and neck lesions. There is controversy surrounding this method in salivary lesions, but recent data indicates it can be just as reliable as in other locations. CONCLUSIONS: Here, we highlight a patient with a salivary duct cyst presenting as a parapharyngeal mass, which has not been described in the literature. Overall, FNA in salivary lesions is highly pathologist dependent, which likely contributes to varying accuracy in the literature.

Prediction of Malignancy in Salivary Gland Tumors by a New Cytology Reporting System.

OBJECTIVES: The aim of this study was to analyze the risk of malignancy in salivary gland tumors on the basis of the Milan System for Reporting Salivary Gland Cytopathology. METHODS: A retrospective review was performed of the charts of patients with salivary gland tumors in whom the final diagnosis was confirmed by surgical excision. Preoperative fine needle aspiration results were categorized according to the Milan System for Reporting Salivary Gland Cytopathology: non-diagnostic (category I), nonneoplastic (category II), atypia of undetermined significance (category III), neoplasm (category IV), suspicious for malignancy (category V), and malignant (category VI). Fine needle aspiration and final diagnosis were compared, and the risk of malignancy and operative/oncological outcomes were analyzed. RESULTS: A total of 288 patients were enrolled in this study. Postoperative histopathologic salivary gland malignancies were found in 30 (10.4%) patients. Risk of malignancy was 7.1%, 0%, 48.0%, 4.8%, 88.7%, and 100% in categories I, II, III, IV, V, and VI, respectively. The most common malignant tumor in category III was salivary duct carcinoma (37.5%), followed by acinic cell carcinoma (25.0%), mucoepidermoid carcinoma (25.0%), and squamous cell carcinoma (12.5%). The 5-year survival rate of patients with malignant tumors showed no statistical difference between category III and category V/VI (P = .140). Risk of malignancy was 88.9% and 100% in category V and VI, respectively. CONCLUSIONS: A half of atypia of undetermined significance (category III) cases were malignant. Once diagnosed, the prognosis of malignant tumor in category III was similar with that in category V/VI.

Myoepithelial sialadenitis with metachromatic matrix: A diagnostic pitfall. A case of salivary gland swelling in a paediatric patient evaluated by fine needle aspiration cytology.

Fine needle aspiration cytology (FNAC) is generally characterized by a high diagnostic accuracy in differentiating non-neoplastic/inflammatory lesions from neoplastic lesions of the salivary glands. Lymphoepithelial sialadenitis/myoepithelial sialadenitis is exceedingly rare in paediatric patients and is characterized by a diffuse, often bilateral, salivary gland enlargement and the differential diagnosis may sometimes be difficult. We report the case of a 10-year-old boy who presented with a swelling of the left parotid gland investigated by ultrasound salivary gland FNAC.

Supraglottic subepithelial benign mass lesions: Focus on clinical features of sialolipoma-like lesion.

OBJECTIVES: Sialolipoma has been classified as a benign soft tissue lesion in the 2017 World Health Organization classification of head and neck tumors. To our knowledge, only one case of laryngeal sialolipoma has been reported in the English literature. We conducted a retrospective study to identify clinical characteristics of supraglottic sialolipoma-like lesion and differentiate it from other supraglottic subepithelial masses. METHODS: Medical records of 16 patients with supraglottic subepithelial benign mass lesions who underwent histological evaluation between 2003 and 2019 were retrospectively analyzed. Sialolipoma-like lesion was defined as a local finding of a well-circumscribed gross mass with pathological presence of salivary gland-like parenchymal lobules with evenly interspersed adipose tissue. RESULTS: Eight patients showed histological positivity for sialolipoma-like lesion, 3 for amyloidosis, 2 for hemangioma, and 1 each for cyst, lymphoid hyperplasia, and chondrometaplasia. Sialolipoma-like lesion tended to be predominant among men; those affected had a mean age of 52.8 (range, 39-74) years. By contrast, among patients with amyloidosis, the ratio of men to women was 1:2 (100% vs. 33%; p = 0.055). Fiberscopic examination of all patients with sialolipoma-like lesions identified well-circumscribed, yellowish masses, closely resembling local amyloidosis findings. Sialolipoma-like lesion was associated with a significantly higher body-mass index (BMI; 27.4 ± 2.8 kg/m2) than amyloidosis (21.6 ± 1.4 kg/m2; p = 0.014). The transoral approach was used for lesion resection in all patients with sialolipoma-like lesion. No patient experienced postoperative recurrence. CONCLUSION: Laryngeal sialolipoma-like lesion might be more prevalent than was previously reported, and histological examination is important to differentiate it from amyloidosis. Supraglottic sialolipoma-like lesion must be differentially diagnosed in patients with high BMI presenting with well-circumscribed, yellowish supraglottic masses.

Fine-needle aspiration cytology in the diagnosis of salivary gland lesions. The role of the Milan system for reporting cytopathology / Citología por aspiración con aguja fina en el diagnóstico de las lesiones de las glándulas salivales. El papel del sistema Milán en citopatología

BACKGROUND: Fine needle aspiration cytology (FNAC) is an established technique in the management of salivary gland lesions. The Milan System for reporting salivary gland cytopathology (MSRSGC) intents to standardize diagnostic categories. Current studies are trying to evaluate the diagnostic approach of this system. METHODS: FNAC of salivary gland lesions were retrieved over an 11-year period. 185 FNAC specimens from 182 patients were reviewed blindly and classified according to the criteria established by the MSRSGC. 136 (74.7%) patients had follow-up of their processes. RESULTS: The total number of diagnostic categories and risk of malignancy (ROM) in 185 specimens were the following: non-diagnostic 39 (21.1%; ROM 12%), non-neoplastic 35 (18.9%; ROM 0%), atypia of undetermined significance (AUS) 17 (9.2%; ROM 46.1%), benign neoplasm 75 (40.5%; ROM 4.9%), salivary gland neoplasm of uncertain malignant potential 4 (2.2%; ROM 100%), suspicious for malignancy 7 (3.8%; ROM 100%), malignant 8 (4.3%; ROM 100%). No false positives were observed in groups IVb, V, and VI in this series. The overall sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy were 88%, 91.8%, 96.3%, 76.7%, and 91% respectively. CONCLUSION: The ROM reported in our study was in keeping with ROM published by the MSRSGC. This system provides standardized information for risk stratification. The category AUS encompassed cases causing uncertainty representing a challenge in management. Defining criteria for AUS category need to be refined. The system facilitates communication between pathologists and clinicians favoring improvement in patient care

ANTECEDENTES: La citología por punción-aspiración con aguja fina (PAAF) está establecida en el tratamiento de las lesiones de las glándulas salivales. El sistema Milán (SM) intenta homogeneizar las categorías diagnósticas en los informes citológicos. Los estudios actuales están tratando de evaluar el enfoque diagnóstico de este sistema. MÉTODOS: Se revisaron las PAAF de las glándulas salivales obtenidas durante un período de 11 años. Se revisaron a ciegas 185 muestras de PAAF de 182 pacientes, y se clasificaron de acuerdo con los criterios establecidos por el SM. Se realizó seguimiento de los procesos de 136 (74,7%) pacientes. RESULTADOS: Los totales de categorías diagnósticas y el riesgo de malignidad (ROM) en 185 muestras fueron los siguientes: no diagnóstico 39 (21,1%; ROM 12%), no neoplásico 35 (18,9%; ROM 0%), atipia de significación indeterminada (ASI) 17 (9,2%; ROM 46,1%), neoplasia benigna 75 (40,5%; ROM 4.9%), neoplasia de potencial maligno incierto 4 (2,2%; ROM 100%), sospecha de malignidad 7 (3,8%; ROM 100%), malignidad 8 (4,3%; ROM 100%). No se observaron falsos positivos en los grupos IVb, V y VI. Los valores de sensibilidad, especificidad, el valor predictivo negativo, el valor predictivo positivo y la precisión diagnóstica fueron del 88%, 91,8%, 96,3%, 76,7% y 91%, respectivamente. CONCLUSIÓN: El ROM observado concordaba con el ROM publicado por el SM. Este proporciona información estandarizada para la estratificación del riesgo. La categoría ASI abarcó los casos que causaron incertidumbre, y representa un desafío en el manejo de los pacientes. Los criterios de definición de ASI deberían perfeccionarse. El sistema facilita la comunicación entre patólogos y clínicos, y mejora la atención al paciente

Experimental Animal Model Systems for Understanding Salivary Secretory Disorders.

Salivary secretory disorders are life-disrupting pathologic conditions with a high prevalence, especially in the geriatric population. Both patients and clinicians frequently feel helpless and get frustrated by the currently available therapeutic strategies, which consist mainly of palliative managements. Accordingly, to unravel the underlying mechanisms and to develop effective and curative strategies, several animal models have been developed and introduced. Experimental findings from these models have contributed to answer biological and biomedical questions. This review aims to provide various methodological considerations used for the examination of pathological fundamentals in salivary disorders using animal models and to summarize the obtained findings. The information provided in this review could provide plausible solutions for overcoming salivary disorders and also suggest purpose-specific experimental animal systems.

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

OBJECTIVES: To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. METHODS: Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and in situ hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. RESULTS: Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4+CXC-motif chemokine receptor 5 (CXCR5)+programmed cell death protein 1 (PD1)+ICOS+ Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4+CD45RO+ICOS+PD1+ cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5+CD4+PD1+ICOS+Foxp3- Tfh-cells and a uniquely expanded population of CXCR5-CD4+PD1hiICOS+Foxp3- Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in ex vivo SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). CONCLUSIONS: Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.

Salivary dysfunction caused by medication usage.

A considerable number of patients arriving in dental offices are being treated with ongoing medication for a variety of chronic diseases. As a result, dentists must be familiar with the potential side effects these therapeutic agents may have on the tissues of the oral cavity, and in particular on the salivary gland. Salivary gland function may be altered by a wide range of medications, leading to effects such as xerostomia, hyposalivation, hypersalivation or even swelling of the glands. These disorders can cause a variety of other health complications. This review will focus on the most common groups of drugs responsible for salivary gland dysfunction, including psychoactive drugs, antidepressants, antipsychotics, antihypertensives, and antihistamines.