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Introduction: Almost one-quarter of immune checkpoint inhibitor (ICI) recipients experience sicca syndrome, while Sjögren's disease (SjD) is estimated at 0.3–2.5%, possibly underreported. Areas covered: This narrative review (Medline/Embase until January/31/2024) addresses the pathophysiology, incidence, demographic/clinical features, biomarkers, labial salivary gland biopsy (LSGB), fulfillment of the idiopathic SjD (iSjD) classificatory criteria, differential diagnosis, and management of sicca syndrome/SjD associated with ICIs. Expert opinion: SjD associated with ICIs is underdiagnosed, since studies that performed the mandatory SjD investigation identified that 40–60% of patients with sicca syndrome associated with ICIs meet the iSjD classificatory criteria. LSGB played a fundamental role in recognizing these cases, as most of them had negative anti-Ro/SS-A antibody. Despite the finding of focal lymphocytic sialoadenitis in LSGB samples mimicking iSjD, immunohistochemical analysis provided novel evidence of a distinct pattern for sicca syndrome/SjD associated with ICIs compared to iSjD. The former has scarcity of B lymphocytes, which are a hallmark of iSjD. Additionally, patients with sicca syndrome/SjD associated with ICIs have demographical/clinical/serological and treatment response dissimilarities compared to iSjD. Dryness symptoms are more acute in the former than in iSjD, with predominance of xerostomia over xerophthalmia, and partial/complete response to glucocorticoids. Dryness symptoms in ICI-treated patients warrant prompt SjD investigation. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS), a chronic autoimmune condition, has been associated with an increased risk of several cancers. This study aims to delve into the relationship between pSS and the potential development of non-Hodgkin's lymphoma (NHL) utilizing an in-depth systematic review and meta-analysis approach. To thoroughly explore the topic, we conducted a thorough examination of the literature, drawing from reputable databases such as ProQuest, PubMed, Web of Science, Cochrane, and Google Scholar. Our data collection spanned until February 8, 2024, with no time limitation. Data were analyzed with Stata 14 software at a significance threshold of p < 0.05. We examined 15 cohort studies encompassing a total of 50,308 individuals from 1997 to 2023. The findings revealed a substantial link between pSS and the risk of NHL, evident across all demographics. Specifically, the standardized incidence ratio (SIR) was generally 8.78 (95% CI 5.51, 13.99), with similar trends observed in both men (SIR, 6.29; 95% CI 1.93, 20.51) and women (SIR, 9.60; 95% CI 5.89, 15.63). Additionally, the SIR (10.50 (95% CI 7, 15.75)), HR (2.82 (95% CI 1.28, 6.18)), and OR (10.50 (95% CI 3.04, 36.28)) indices further supported this association. Furthermore, the risk of non-NHL associated with pSS was noticeable across different age groups of 40–49 years (SIR, 30.13; 95% CI 14.62, 62.08), 50–59 years (SIR, 9.12; 95% CI 5.13, 16.19), and 60–69 years (SIR, 9; 95% CI 4.68, 17.32). pSS substantively augments the likelihood of NHL manifestation. It notably impacts females and those in earlier stages of adulthood with more acuity than males and older cohorts. [ABSTRACT FROM AUTHOR]

The frequency of antibodies to Ku varies in various autoimmune diseases. In 2019, Spielmann et al. identified two types of anti-Ku syndrome based on a hierarchical clustering analysis. Sjögren's syndrome occurs both in the first type of anti-Ku syndrome and in the second type. Despite the fact that increased tissue expression of Ku proteins was noted in lymphocytic cells with focal sialoadenitis of the minor salivary glands in patients with primary Sjogren's syndrome, only 49 cases of a combination of anti-Ku antibodies and manifestations of Sjogren's syndrome have been described in the literature. Some researchers examined patients for the presence of Sjogren's syndrome only if they had anti-Ro or anti-La antibodies, although in the literature, there are descriptions of Sjogren's syndrome in the presence of only isolated anti-Ku antibodies, as in our case. Literature data on glandular and extraglandular manifestations of Sjögren's syndrome in anti-Ku-positive patients are limited. Below, we present the first case of Sjögren's syndrome in combination with the first type of anti-Ku syndrome complicated by the development of mucosa-associated lymphoid tissue (MALT) lymphoma. The article also provides a systematic review of the literature on the association of Sjögren's syndrome with anti-Ku antibodies. [ABSTRACT FROM AUTHOR]

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Key Clinical Message Several reports of suspected oral and ocular manifestations of coronavirus disease 2019 (COVID‐19) has prompted investigations into ocular signs, symptoms, and transmission (5).11.2% of patients with COV19 infection had ocular symptoms, including ocular pain, conjunctivitis, dry eye, and floaters, meanwhile, many studies had documented oral symptoms such as dry mouth and dysgeusia in these patients. Our case reported a 39‐year‐old male, presented with symptoms of dry mouth and dry eye lasting more than 3 months. The patient had recovered from (PCR‐confirmed) COVID‐19 which lasted 10 days, 4 months ago. The physical examination was normal. Ocular findings include conjunctival hyperemia and superficial punctate keratitis. The anti‐nuclear antibody (ANA) was weekly positive at 1/80. Schirmer test considered positive. He continued on 200 mg/day of hydroxychloroquine, along with tear drops until now with remission. Sicca symptoms may be a sequel of COVID‐19 infection, and physicians should be aware of this sequel. The sequela of this infection is not understood, with limited data in the literature. Future prospective cohort studies are needed to reveal the impact of these features on oral health.

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren’s syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy.

Key Clinical Message: Several reports of suspected oral and ocular manifestations of coronavirus disease 2019 (COVID‐19) has prompted investigations into ocular signs, symptoms, and transmission (5).11.2% of patients with COV19 infection had ocular symptoms, including ocular pain, conjunctivitis, dry eye, and floaters, meanwhile, many studies had documented oral symptoms such as dry mouth and dysgeusia in these patients. Our case reported a 39‐year‐old male, presented with symptoms of dry mouth and dry eye lasting more than 3 months. The patient had recovered from (PCR‐confirmed) COVID‐19 which lasted 10 days, 4 months ago. The physical examination was normal. Ocular findings include conjunctival hyperemia and superficial punctate keratitis. The anti‐nuclear antibody (ANA) was weekly positive at 1/80. Schirmer test considered positive. He continued on 200 mg/day of hydroxychloroquine, along with tear drops until now with remission. Sicca symptoms may be a sequel of COVID‐19 infection, and physicians should be aware of this sequel. The sequela of this infection is not understood, with limited data in the literature. Future prospective cohort studies are needed to reveal the impact of these features on oral health. [ABSTRACT FROM AUTHOR]

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren's syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy. [ABSTRACT FROM AUTHOR]

In this report, we present a patient with metastatic non-small cell lung cancer who developed Sjögren’s syndrome secondary to immune checkpoint inhibition. This patient had a typical clinical presentation as well as biochemical signature, developing only 18 months after the start of treatment with PD-1 inhibition (pembrolizumab).

Background: To investigate the associations between extrahepatic manifestations, autoantibodies, and viremia in patients with hepatitis C virus (HCV) infection. Methods: This cross-sectional study recruited patients with HCV infection from the outpatient department of a tertiary medical center in Northern Taiwan between January 2017 and August 2019. Autoantibody profiles and the clinical parameters of HCV infection were evaluated using laboratory tests, and a questionnaire was used to record extrahepatic manifestations. HCV infection status, including inactive HCV infection, active hepatitis, and cirrhosis, was defined according to abdominal ultrasonography findings and alanine transaminase levels. Results: A total of 77 patients with HCV were recruited, with 19.5% and 16.9% of patients, respectively, presenting with arthritis and dry eyes. Autoantibody screening revealed rheumatoid factor (RF), antinuclear antibody (ANA), anti-Ro antibody, and anti-La antibody positivity in 20.8%, 23.4%, 13.0%, and 2.6% of the patients, respectively. The presence of RF was associated with arthritis, whereas the presence of ANA was associated with dry eyes but not dry mouth. Active hepatitis and HCV-related cirrhosis were associated with viremia, but not autoantibody profiles. Conclusion: In this single-center study, the prevalence of extrahepatic manifestations and autoantibodies did not differ in patients stratified by the HCV infection status. Rheumatic manifestations were associated with the presence of autoantibodies but not with viremia.

Polyuria-polydipsia syndrome is a frequent symptom in pediatrics, primarily attributed to diabetes mellitus. In the context of diabetes insipidus, this syndrome can stem from central or nephrogenic factors. Sjögren's syndrome, an uncommon autoimmune disease in children, can affect multiple organs. Kidney involvement as described in adults is usually related to glomerular or tubular impairment, often linked to distal tubular acidosis. As a kidney involvement during childhood, Sjögren's syndrome has rarely been reported. Hereby, we present the case of Sjögren's syndrome revealed by polyuria-polydipsia syndrome in a 10-year-old boy. [ABSTRACT FROM AUTHOR]

Objective: Sjogren's syndrome (SS) is an autoimmune disease that mainly affects the salivary and lacrimal glands and further leads to dry mouth and eyes. In recent years, knowledge about the treatment of SS is developing rapidly. This study aims to assess research progress on SS treatment using a bibliometric approach and to identify research hotspots and emerging trends in this area. Methods: The publications related to the treatment of SS were retrieved from the Science Citation Index Expanded (SCI-E) database. The following search terms were used to extract document data: TS=(Sjogren* OR Sicca*) AND TS= (Treat* OR Therap* OR Disease Management). Articles and review articles published in English from 1900 to 2022 were selected. After the manual screening, the publication data were exported to a plain text file and applied for cooperative network analysis, keyword analysis, and reference co-citation analysis by using CiteSpace. Results: A total of 2038 publications were included in the analysis from 571 journals by 9063 authors. The annual number of published studies and times cited showed an overall upward trend since 1992. There was a degree of national/regional collaboration in this area, but direct collaboration between institutions and authors was still lacking. The country with the highest number of publications was in the United States, followed by China and Japan. Five SS-related treatments as the research hotspots were summarized by analyzing keywords and references, including immunosuppressive and anti-inflammatory therapy, regenerative therapy, gene therapy, surgical treatment, and symptomatic treatment. Among them, B cells, T cells, mucosal-associated invariant T (MAIT) cells, mesenchymal stem cells (MSCs), rituximab, belimumab, cell-target therapy, and immunosuppressive and anti-inflammatory therapy were emerging trends in this field. Conclusions: This study conducted a data-based and objective introduction to the treatment of SS from a fresh perspective. An analysis of the intellectual bases, research hotspots, and emerging trends in the field will contribute to future research and treatment decisions, which will ultimately benefit SS patients.

Objective: One‐third of the Hungarian population suffers from xerostomia. Since there is no evidence of the actual prevalence of Sjögren's syndrome (SS) in Hungary, this study aimed to evaluate the same. Materials and Methods: Data were collected from the Faculty of Dentistry, Semmelweis University from 2008 to 2015. A diagnosis of SS was established based on the American College of Rheumatology and European League Against Rheumatism criteria. Results: Of the 1076 patients examined with sicca symptoms, 188 patients had confirmed SS. Primary SS (pSS) was diagnosed in 135 patients and secondary SS (sSS) was confirmed in 53 patients. According to the available statistical records of the public health service of Hungary, there were an average of 16 (0.0014%, 5–26) newly diagnosed SS cases in the entire population and 141 SS patient‐practitioner consultations (49–232) per 100,000 inhabitants in the country over the past 10 years (based on the past 10 years: 2011–2020). Conclusion: Results revealed that approximately 1/5th–1/6th of patients with sicca symptoms have SS, among whom 72% and 285 have pSS and sSS, respectively. Global Hungarian records simultaneously revealed that the number of both new diagnoses and doctor‐SS patient encounters has significantly decreased (by 50%) yearly over the last decade. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chronic Graft-versus-Host Disease (cGVHD) is a major long-term complication, associated with morbidity and mortality in patients following allogenic hematopoietic cell transplantation (HCT) for immune hematopoietic disorders. The mouth is one of the most frequently affected organs after HCT (45-83%) and oral cGVHD, which may appear as the first visible sign. Manifestations present with mucosal lichenoid lesions, salivary gland dysfunction and limited oral aperture. Diagnosis of oral cGVHD severity is based on mucosal lesions with symptoms of sensitivity and pain and reduced oral intake. However, diagnostic difficulties arise due to subjective definitions and low specificity to cover the spectrum of oral cGVHD. In recent years there have been significant improvements in our understanding of the underlying oral cGVHD disease mechanisms. Drawing upon the current knowledge on the pathophysiology and biological phases of oral cGVHD, we address oral mucosa lichenoid and Sjogren's Syndrome-like sicca syndromes. We consider the response of alloreactive T-cells and macrophages to recipient tissues to drive the pathophysiological reactions and biological phases of acute inflammation (phase 1), chronic inflammation and dysregulated immunity (phase 2), and subsequent aberrant fibrotic healing (phase 3), which in time may be associated with an increased malignant transformation rate. When formulating treatment strategies, the pathophysiological spectrum of cGVHD is patient dependent and not every patient may progress chronologically through the biological stages. As such there remains a need to address and clarify personalized diagnostics and management to improve treatment descriptions. Within this review, we highlight the current state of the art knowledge on oral cGVHD pathophysiology and biological phases. We address knowledge gaps of oral cGVHD, with a view to facilitate clinical management and improve research quality on lichenoid biology and morbid forms of oral cGVHD. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome (SS) is an autoimmune disease that affects exocrine glands, mainly salivary and lacrimal glands. Several studies have investigated cytokine profiles in tears in order to understand the pathogenesis of SS and find additional diagnostic markers. This systematic review and meta-analysis aimed to analyze cytokines in tears of SS patients. A systematic literature search of the Cochrane, Medline via PubMed, Scopus, and Web of Science databases was conducted using key terms related to "Sjögren's syndrome" and "tears" combined with "biomarker", "cytokines", "interleukin", and "chemokines", following PRISMA guidelines. Article selection was subjected to certain eligibility criteria. A total of 17 articles (from 1998 and 2022) were selected for the quantitative and qualitative analysis. When compared to controls, concentrations of IFN-γ, TNF-α, IL-1α, IL-1 Ra, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21 and IL-22 were consistently higher; however, IL-23 was significantly lower in patients with SS compared to the controls. Tear levels of some cytokines were significantly elevated among SS groups compared to control groups. Therefore, these cytokines could be potential biomarkers of SS. However, standardization of sample collection and analytical methods is necessary in order to translate these findings into clinical practice. [ABSTRACT FROM AUTHOR]

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target. [ABSTRACT FROM AUTHOR]

Introduction Dry mouth is the main symptom of sicca syndrome, which rarely occurs as an immune‐related adverse event. Here we report a case of sicca syndrome caused by immune checkpoint inhibitor treatment. Case presentation A 70‐year‐old man was diagnosed with left renal cell carcinoma after radical left nephrectomy. Nine years later, computed tomography revealed a metastatic nodule in the upper left lung lobe. Subsequently, ipilimumab and nivolumab were administered for recurrent disease. After 13 weeks of treatment, xerostomia and dysgeusia were noted. Salivary gland biopsy revealed lymphocyte and plasma cell infiltration in the salivary glands. Sicca syndrome was diagnosed and pilocarpine hydrochloride was prescribed without corticosteroids, with continuation of immune checkpoint inhibitor therapy. The symptoms alleviated after 36 weeks of treatment, with shrinkage of the metastatic lesions. Conclusion We experienced sicca syndrome caused by immune checkpoint inhibitors. Sicca syndrome improved without steroids and the immunotherapy could be continued.

SSc is an auto-immune disease characterized by life-threatening manifestations such as lung fibrosis or pulmonary arterial hypertension. Symptoms with a detrimental impact on quality of life are also reported and sicca syndrome (xerostomia, xeropthalmia) is present in up to 80% of patients with SSc. Sicca syndrome can occur in the absence of overlap with Sjögren's disease and recent studies highlight that fibrosis of minor and major salivary glands, directly linked to the pathogenesis of SSc, could be a major contributor of xerostomia in SSc. This narrative review provides an overview of the clinical presentation, diagnostic strategies, management and future perspectives on sicca syndrome in patients with SSc. [ABSTRACT FROM AUTHOR]

Chronic Graft-versus-Host Disease (cGVHD) is a major long-term complication, associated with morbidity and mortality in patients following allogenic hematopoietic cell transplantation (HCT) for immune hematopoietic disorders. The mouth is one of the most frequently affected organs after HCT (45-83%) and oral cGVHD, which may appear as the first visible sign. Manifestations present with mucosal lichenoid lesions, salivary gland dysfunction and limited oral aperture. Diagnosis of oral cGVHD severity is based on mucosal lesions with symptoms of sensitivity and pain and reduced oral intake. However, diagnostic difficulties arise due to subjective definitions and low specificity to cover the spectrum of oral cGVHD. In recent years there have been significant improvements in our understanding of the underlying oral cGVHD disease mechanisms. Drawing upon the current knowledge on the pathophysiology and biological phases of oral cGVHD, we address oral mucosa lichenoid and Sjogren’s Syndrome-like sicca syndromes. We consider the response of alloreactive T-cells and macrophages to recipient tissues to drive the pathophysiological reactions and biological phases of acute inflammation (phase 1), chronic inflammation and dysregulated immunity (phase 2), and subsequent aberrant fibrotic healing (phase 3), which in time may be associated with an increased malignant transformation rate. When formulating treatment strategies, the pathophysiological spectrum of cGVHD is patient dependent and not every patient may progress chronologically through the biological stages. As such there remains a need to address and clarify personalized diagnostics and management to improve treatment descriptions. Within this review, we highlight the current state of the art knowledge on oral cGVHD pathophysiology and biological phases. We address knowledge gaps of oral cGVHD, with a view to facilitate clinical management and improve research quality on lichenoid biology and morbid forms of oral cGVHD.

In this report, we present a patient with metastatic non-small cell lung cancer who developed Sjögren's syndrome secondary to immune checkpoint inhibition. This patient had a typical clinical presentation as well as biochemical signature, developing only 18 months after the start of treatment with PD-1 inhibition (pembrolizumab). [ABSTRACT FROM AUTHOR]

Cancer immunotherapy, which seeks to stimulate a patient's own immune system to combat cancer, is quickly becoming a central pillar of cancer therapeutics and has resulted in the development of many novel anticancer therapies. One subtype of cancer immunotherapy, immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment and changed the standard of care for multiple indications. However, the advent of ICIs has produced a wide variety of inflammatory side effects termed immune‐related adverse events (IRAEs), including ICI‐induced Sicca syndrome. This article outlines the clinical features of ICI‐induced Sicca syndrome and assesses its reported incidence in clinical trials, case series, and case reports across numerous cancers and treatment modalities. Presentations of ICI‐induced Sicca syndrome in patients with pre‐existing Sjӧgren's disease and with extra‐glandular manifestations will also be explored. The pathophysiological mechanisms underlying IRAEs, including ICI‐induced Sicca syndrome, will be evaluated through an examination of existing literature. Finally, the various treatment and management strategies as well as aims for future work will be discussed and reviewed. [ABSTRACT FROM AUTHOR]

• Objective clinical, histological and US manifestations of sicca syndrome are highly frequent in SSc patients. • Sjogren-SSc patients (overlap) had more severe glandular involvement than isolated Sjogren and isolated Sicca-SSc patients. • Specific SSc US patterns of salivary gland involvement are still to be defined. This study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes. Sixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc). SSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure. SjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract Objectives To assess the prevalence and determinants of xerostomia among adults and identify how many of the ones experiencing xerostomia have Sicca and Sjogren's syndromes. Materials and methods This cross-sectional study included 1405 35–74-year-old Lithuanians (51.7% response rate) from the five largest Lithuanian cities and 10 peri-urban and rural areas that were randomly selected from each of the 10 Lithuanian counties. Xerostomia was determined by the self-reported experience of dry mouth as "often" or "always". A dentist diagnosed Sicca syndrome by unstimulated whole sialometry and the Schirmer's test, and all cases were referred to a rheumatologist to confirm Sjogren's syndrome. Self-reported questionnaires collected data about the determinants. Results The prevalence of xerostomia was 8.0% (n = 112), Sicca syndrome was diagnosed for 8 participants (0.60%), and Sjogren's syndrome for 2 participants (0.14%), with this being the first time it was diagnosed. Experiencing xerostomia was associated with older age (OR 1.7, 95% CI 1.1–2.6), urban residence (OR 3.3, 95% CI 1.6–5.0), presence of systemic diseases (OR 2.5, 95% CI 1.4–3.3), and the use of alcohol (OR 0.6, 95% CI 0.4–0.9). The higher proportion of participants with Sicca syndrome involved females, of older age, having systemic diseases, and using medications. Conclusions The prevalence of xerostomia was 8.0% and the determinants of xerostomia were older age, urban residence, systemic diseases, and absence of using alcohol. In total, 0.6% of participants had Sicca syndrome, which was more prevalent among females, older subjects, those with systematic diseases, and those using medications. Sjogren's syndrome was diagnosed in 0.14% of participants. Clinical relevance Dental clinicians need to be trained to identify potential Sjogren's syndrome cases.

The article discusses the importance of ultrasound examination of the salivary glands in Sjogren’s disease for the diagnosis, as well as for assessing the activity of the disease. The characteristics of the main ultrasound changes in the salivary glands and the pathogenetic reasons of these changes are given. The results of studies of the dynamics of changes in ultrasound parameters both in patients not receiving treatment and in the presence of various methods of therapy are presented. The paper also provides basic data on the role of ultrasound in the differential diagnosis of diseases involving the salivary glands.

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune rheumatic disease where xerophthalmia, xerostomia and presence of anti-SSA and anti-SSB antibodies are typical features. Its prevalence is higher in over-65 aged population than in other age groups. In the elderly, pSS diagnosis comes up against a whole series of critical points that may favor its misdiagnosis. The aim of our article is to discuss the most relevant of them: the frequent occurrence of a seronegative subset, the presence of systemic features not related to sicca syndrome, the sicca syndrome as iatrogenic manifestation and the possibility of a biopsy false negative of labial salivary glands.

Sjogren’s syndrome (SS) is an autoimmune disease that affects exocrine glands, mainly salivary and lacrimal glands. Several studies have investigated cytokine profiles in tears in order to understand the pathogenesis of SS and find additional diagnostic markers. This systematic review and meta-analysis aimed to analyze cytokines in tears of SS patients. A systematic literature search of the Cochrane, Medline via PubMed, Scopus, and Web of Science databases was conducted using key terms related to “Sjögren’s syndrome” and “tears” combined with “biomarker”, “cytokines”, “interleukin”, and “chemokines”, following PRISMA guidelines. Article selection was subjected to certain eligibility criteria. A total of 17 articles (from 1998 and 2022) were selected for the quantitative and qualitative analysis. When compared to controls, concentrations of IFN-γ, TNF-α, IL-1α, IL-1 Ra, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21 and IL-22 were consistently higher; however, IL-23 was significantly lower in patients with SS compared to the controls. Tear levels of some cytokines were significantly elevated among SS groups compared to control groups. Therefore, these cytokines could be potential biomarkers of SS. However, standardization of sample collection and analytical methods is necessary in order to translate these findings into clinical practice.

Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.

Le syndrome de Gougerot-Sjögren (SGS) est une maladie auto-immune systémique dont le diagnostic est parfois tardif et difficile à établir en raison de présentations cliniques très variées. Le SGS peut être primitif ou associé à une autre maladie auto-immune systémique ou spécifique d'organe. Le tableau clinique caractéristique associe un syndrome sec oculo-buccal à une asthénie et des douleurs articulaires et musculaires. Une atteinte systémique est observée chez plus d'un tiers des patients dont le lymphome, pouvant révéler la maladie. Des critères internationaux consensuels ont été établis pour permettre de faire un diagnostic de certitude, afin de pouvoir proposer, le plus précocement possible, un suivi et des mesures thérapeutiques adaptées. Ces critères, qui prennent en compte des paramètres cliniques, immunologiques et histologiques, sont facilement utilisables en pratique courante, et permettent également d'éliminer les nombreux diagnostics différentiels d'un syndrome sec. L'association du SGS à une autre maladie auto-immune systémique (lupus, polyarthrite rhumatoïde, sclérodermie systémique,...) mérite d'être identifiée car le SGS et la maladie auto-immune associée peuvent mutuellement modifier leurs profils cliniques, biologiques et évolutifs. Ainsi, le concept de SGS « secondaire » a-t-il évolué vers celui de SGS « associé ». Sjögren's syndrome (SS) is a systemic autoimmune disease for which diagnosis is difficult and often delayed because of its highly variable clinical presentation. SS may be primary (pSS) or associated with another systemic or organ-specific autoimmune disease. The typical clinical presentation is a dry oculo-buccal syndrome associated with fatigue and joint and muscle pain. Systemic involvement is seen in more than one third of patients, including lymphoma, and may reveal the disease. International consensus criteria have been established to enable a reliable diagnosis to be made, so that follow-up and appropriate therapeutic measures can be proposed as early as possible. These criteria, which take into account clinical, immunological and histological parameters, are easily applicable in everyday practice, and also make it possible to eliminate the many differential diagnoses of a dry syndrome. The association of SS with another systemic autoimmune disease (lupus, rheumatoid arthritis, systemic scleroderma,...) should be investigated because SS and the associated autoimmune disease may mutually modify their clinical, biological and evolutionary profiles. This leads to the evolution of the concept of "secondary" SS towards that of "associated" SS. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is the most common blood-borne chronic infection in the United States. Chronic lymphocytic sialadenitis and sicca syndrome have been reported in chronic HCV infection. Up to 55% of these patients may have xerostomia; the mechanisms of the xerostomia and salivary gland (SG) hypofunction remain controversial. The objectives of this project are to establish if xerostomia associates with SG and HCV infection and to characterize the structural changes in SG and saliva composition. Eighteen HCV-infected patients with xerostomia were evaluated for SG dysfunction; 6 of these patients (patients 1–6) were further evaluated for SG histopathological changes and changes in saliva composition. The techniques used include clinical and laboratory assessment, SG ultrasonography, histological evaluation, sialochemical and proteomics analysis, and RNA in situ hybridization. All the HCV patients had low saliva flow, chronic sialadenitis, and SG fibrosis and lacked Sjögren syndrome (SS) characteristic autoantibodies. Further evaluation of a subgroup of 6 HCV patients (patients 1–6) demonstrated diffuse lymphocytic infiltrates that are predominantly CD8+ T cells with a significant increase in the number of inflammatory cells. Alcian Blue/periodic acid–Schiff staining showed significant changes in the ratio and intensity of the acinar secretory units of the HCV patients' minor SG. The submandibular glands showed significant ultrasonographic abnormalities in the parenchyma relative to the parotid glands. Significant changes were also observed in the concentration of sodium and mucin 5b. Although no significant correlation was observed between the lymphocytic infiltrates and the years of HCV chronic infection, a positive correlation was observed between HCV RNA–positive epithelial cells and the years of HCV infection. Consistent with the low saliva flow and xerostomia, patients showed changes in several markers of SG acinar and ductal function. Changes in the composition of the saliva suggest that HCV infection can cause xerostomia by mechanisms distinct from SS. [ABSTRACT FROM AUTHOR]

Purpose: Xerostomia is an underrecognized adverse effect of immunotherapy (IO) that can significantly impact patients' quality of life by leading to poor nutritional status, dental caries, and oral candidiasis. The purpose of this case series was to describe the onset, severity, clinical course, and management of IO-induced xerostomia. Methods: This was a retrospective case series conducted at an outpatient cancer center. Data collection was conducted via chart review. The severity of dry mouth symptoms was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: Six patients with advanced solid tumors who received a PD-1 inhibitor or PD-1/CTLA-4 inhibitor combination therapy were evaluated. The median time to onset of xerostomia was 4.5 months overall, though symptoms developed sooner in patients who received IO as subsequent-line therapy (median = 1.9 months). All patients developed other immune-related adverse events (IRAEs) such as hypothyroidism. Five patients (83%) had grade 2 dry mouth symptoms, and similarly, 5 patients eventually required prescription medications such as sialogogues and topical or systemic corticosteroids to alleviate symptoms. Two patients (33%) required interruptions in IO. All 3 patients who received cevimeline noticed improvement in symptoms, and one patient who received prednisone dosed at 1 mg/kg/day tapered over 5 weeks also experienced significant relief. Conclusion: While the optimal management of IO-induced xerostomia has not yet been established by national guidelines, increased awareness can prompt faster initiation of supportive care measures that can prevent significant discomfort and poor oral intake. Thoughtful use of over-the-counter topical agents, sialogogues, corticosteroids, and treatment interruptions can help improve tolerability of this adverse effect. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome (SS) is an autoimmune disease affecting exocrine glands with known properties to cause chronic systemic multi-organ disease involvement. It produced the typical features of sicca syndrome, but due to insidious onset of the disease, patient may present with complications of the condition at the initial presentation. We present a case of primary Sjogren's syndrome (SS) who first presented with pulmonary manifestations and was subsequently diagnosed as Lymphocytic Interstitial Pneumonia (LIP). The patient was extensively investigated and received appropriate treatment modalities. [ABSTRACT FROM AUTHOR]

Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies—all exerted system's enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a "sick eye in a sick body" makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles. [ABSTRACT FROM AUTHOR]

The objective of this review was to assess and evaluate whether the published diagnostic accuracy studies provide evidence to sustain the current diagnostic guidelines put forth by ACR/EULAR used for patients with suspected Sjögren's syndrome (SS). Literature databases, including Medline, Embase, and EBM Reviews, were searched for relevant studies on the correlation between ACR/EULAR criteria, particularly those with a direct comparison between their accuracy in diagnosing Sjögren's syndrome. We followed Cochrane, QUADAS-2, and STARD guidelines and the four-phase flow diagram by the PRISMA Statement. Reports in several languages, but only human studies were considered. Three studies assessed the accuracy of the current diagnostic tests, and these did not present adequate designs that would allow a well-supported conclusion with a high level of certainty. Due to significant clinical and methodological heterogeneity, a meta-analysis was not performed. A qualitative review of the papers was undertaken. Neither the comparative nor the non-comparative study designs permit conclusive recommendations regarding an alternative diagnostic pathway for SS. Well-designed studies of the diagnostic accuracy of SS tests are needed to validate current guidelines or to suggest changes to the current guidelines. [ABSTRACT FROM AUTHOR]

Purpose The aim was to study the prevalence and related risk factors of dry eye disease (DED) in a random population sample from Cairo and upper Egypt. Materials and methods A clinic-based, cross-sectional, observational, multicenter study was conducted on eyes of healthy individuals accompanying ophthalmological patients coming for ocular examination in outpatient clinics of Ain Shams University Hospital and Al Watany Eye Hospital, Cairo; Saint Mary Hospital, Qena; and Aswan Eye center, Aswan, Egypt. Eyes were selected by systematic random sampling. Two questionnaires were used: the Ocular Surface Disease Index and another one covering medical history and risk factors for DED. External ocular examination, tear film break-up time, and Schirmer’s tests were done. Diagnosis of DED was established on an Ocular Surface Disease Index score of 50 or above associated with at least one of DED symptoms together with either tear film break-up time of less than or equal to 5 s or Schirmer’s test measurement of less than or equal to 10 mm. Results A total of 603 eyes were included; 290 of which were of male participants and 313 were of female ones. The age range was 18–94 years, with a mean age of 50.06±19.06 years. The prevalence of DED was 77.6% (468 eyes). There was a statistically highly significant difference in DED prevalence among all age groups (P

Background: Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS).Methods: Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.Results: A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with more frequent symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/584; 35%), and Dry With Autoimmune Features (DAFpos, 94/584;16%). DAFpos patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8; p < 0.001), most extra-glandular manifestations (p < 0.001), and highest median SGUS Score (DAFpos: 8 [IQR 4–10] vs. SG: 2 [1–4] vs. DAFneg 4 [2–5]; p < 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed.Discussion: SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAFpos cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.

Introduction Sicca syndrome, characterized by xerophthalmia and xerostomia, is associated with various autoimmune and non-autoimmune conditions, posing diagnostic challenges. Sjögren's syndrome (SS) is the most prevalent systemic autoimmune disease linked to sicca symptoms. This study evaluates the diagnostic accuracy of salivary gland scintigraphy (SGS) in distinguishing SS from non-Sjögren's sicca conditions, alongside other diagnostic tests. Methods A retrospective analysis was conducted at Hospital Universitario La Paz from December 2019 to March 2023, including 142 patients diagnosed with sicca syndrome. Correlations between qualitative and quantitative SGS data (GE Healthcare, Chicago, Illinois) and multiparametric sicca evaluations were assessed. Results Among the 142 patients, 84 (59.15%) were classified as having SS, with 55 (65.48%) seropositive for anti-Ro antibodies. Abnormal SGS results were found in 135 (95.07%) patients. Qualitative SGS categorized seven (4.93%) as mild, 53 (37.32%) as moderate, 50 (35.21%) as severe, and 21 (14.79%) as functionally annulled. Moderate or worse impairment had a sensitivity of 0.88 and a specificity of 0.17. Functional annulment had a sensitivity of 0.17 and a specificity of 0.97. Quantitative SGS using ejection fraction thresholds of ≤30% and ≤20% had sensitivities of 0.35 and 0.18 and specificities of 0.84 and 0.94, respectively. Quantitative SGS metrics correlated with unstimulated whole salivary flow (WUSF; 0.243; p=0.003) and inversely with lymphocytic infiltration (-0.281; p=0.001). The 2016 American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) classification criteria for Sjögren's syndrome demonstrated an area under the curve (AUC) of 0.932, which improved to 0.951 with the inclusion of SGS parameters. Conclusions SGS is a significant diagnostic tool in the multiparametric evaluation of sicca syndrome, showing strong correlations with histological and immunological markers. Its integration into diagnostic criteria enhances the differentiation between SS and non-Sjögren's sicca conditions, suggesting its potential inclusion in future classification frameworks., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Hospital Universitario La Paz issued approval PI-5756. The necessary suitability requirements of the protocol in relation to the study objectives are met. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Álvarez Troncoso et al.)

Objectives: To assess the prevalence and determinants of xerostomia among adults and identify how many of the ones experiencing xerostomia have Sicca and Sjogren's syndromes. Materials and methods: This cross-sectional study included 1405 35–74-year-old Lithuanians (51.7% response rate) from the five largest Lithuanian cities and 10 peri-urban and rural areas that were randomly selected from each of the 10 Lithuanian counties. Xerostomia was determined by the self-reported experience of dry mouth as "often" or "always". A dentist diagnosed Sicca syndrome by unstimulated whole sialometry and the Schirmer's test, and all cases were referred to a rheumatologist to confirm Sjogren's syndrome. Self-reported questionnaires collected data about the determinants. Results: The prevalence of xerostomia was 8.0% (n = 112), Sicca syndrome was diagnosed for 8 participants (0.60%), and Sjogren's syndrome for 2 participants (0.14%), with this being the first time it was diagnosed. Experiencing xerostomia was associated with older age (OR 1.7, 95% CI 1.1–2.6), urban residence (OR 3.3, 95% CI 1.6–5.0), presence of systemic diseases (OR 2.5, 95% CI 1.4–3.3), and the use of alcohol (OR 0.6, 95% CI 0.4–0.9). The higher proportion of participants with Sicca syndrome involved females, of older age, having systemic diseases, and using medications. Conclusions: The prevalence of xerostomia was 8.0% and the determinants of xerostomia were older age, urban residence, systemic diseases, and absence of using alcohol. In total, 0.6% of participants had Sicca syndrome, which was more prevalent among females, older subjects, those with systematic diseases, and those using medications. Sjogren's syndrome was diagnosed in 0.14% of participants. Clinical relevance Dental clinicians need to be trained to identify potential Sjogren's syndrome cases. [ABSTRACT FROM AUTHOR]

Background: Sublabial gland biopsy is the 'gold standard' in establishing the diagnosis of primary Sjögren's syndrome. Bleeding and nerve damage are complications. Our centre has adopted the use of the chalazion clamp to provide a dry surgical field to address these challenges. This study aimed to assess the accuracy of minor salivary gland harvest rate using this technique. Method: A retrospective review of all minor salivary gland biopsies was carried out in a single tertiary referral centre over a five-year period. Results: Forty-one biopsy patients were identified, with a mean age of 56.1 years. There was 100 per cent accuracy in harvest rate in our series. Twelve patients (29 per cent) were positive for primary Sjögren's syndrome. No patients had a complication immediately or at one month follow up. Conclusion: Dry surgical field sublabial gland biopsy is a safe and highly effective technique in the diagnosis of primary Sjögren's syndrome. Initial results indicate it may provide a higher harvest rate with fewer complications than traditional non-ischaemic techniques. [ABSTRACT FROM AUTHOR]

The association between estrogen receptor (ER) positive breast cancer (BC) and autoimmune disorders has been recently recognized. In particular exposure to aromatase inhibitors is associated with a significant increased risk of rheumatological autoimmune disorders. The purpose of this study was to investigate Sjogren syndrome (SjS) occurrence in patients with ER-positive BC. This is a prospective study analyzing 110 consecutive patients with ER-positive BC treated with anti-hormonal therapy. New 2016 American College of Rheumatology/European League against Rheumatism (ACR-EULAR) classification criteria were used to identify patients with SjS. Ultrasonography of salivary glands (SG) was used to screen patients with negative disease biomarkers, to candidate them to SGs biopsy. Sicca syndrome was detected in 51 patients (46%), whereas a true primary SjS was diagnosed in 11 patients (10%). Even if the evaluation of incidence and prevalence of primary SjS vary widely, to the best of our knowledge, the data from the present study emphasize a previously unsuspected high prevalence of defined pSjS that causes BC sicca symptoms complaints. Hypothesis, explanation of this link and even possible biases are discussed.

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Abstract Background Distal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities. Case presentation We describe a case of a 57-year-old Caucasian woman with previous episodes of hypokalemia, severe muscle weakness, and fatigue. Upon further questioning, symptoms of dry eye and dry mouth became evident. Initial evaluation revealed hyperchloremic metabolic acidosis, severe hypokalemia, persistent alkaline urine, and a positive urinary anion gap, suggestive of distal renal tubular acidosis. Additional laboratory workup and renal biopsy led to the diagnosis of primary Sjögren’s syndrome with associated acute tubulointerstitial nephritis. After potassium and bicarbonate supplementation, immunomodulatory therapy with hydroxychloroquine, azathioprine, and prednisone was started. Nonetheless, her renal function failed to improve and remained steady with an estimated glomerular filtration rate of 42 ml/min/1.73 m2. The literature on this topic was reviewed. Conclusions Cases of renal tubular acidosis should be carefully evaluated to prevent adverse complications, uncover a potentially treatable condition, and prevent the progression to chronic kidney disease. Repeated episodes of unexplained hypokalemia could be an important clue for diagnosis.