Sicca Symptoms Research Articles

Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies.

In primary Sjögren syndrome (pSS), chronic inflammation of exocrine glands results in tissue destruction and sicca symptoms, primarily of the mouth and eyes. Fatigue, arthralgia and myalgia are also common symptoms, whereas extraglandular manifestations that involve the respiratory, nervous and vascular systems occur in a subset of patients. The disease predominantly affects women, with an estimated female to male ratio of 14 to 1. The aetiology of pSS, however, remains incompletely understood, and effective treatment is lacking. Large-scale genetic and epigenetic investigations have revealed associations between pSS and genes in both innate and adaptive immune pathways. The genetic variants mediate context-dependent effects, and both sex and environmental factors can influence the outcome. As such, genetic and epigenetic studies can provide insight into the dysregulated molecular mechanisms, which in turn might reveal new therapeutic possibilities. This Review discusses the genetic and epigenetic features that have been robustly connected with pSS, putting them into the context of cellular function, carrier sex and environmental challenges. In all, the observations point to several novel opportunities for early detection, treatment development and the pathway towards personalized medicine.

Vaginal dryness in women infected by human T-lymphotropic virus type 1: an exploratory study.

Human T-lymphotropic virus type-1 (HTLV-1) causes a variety of sicca symptoms, including xeroderma, xerostomia, and xerophthalmia. We sought to evaluate vaginal dryness via the degree of perceived vaginal lubrication, vaginal hormonal cytology, and direct measurements of vaginal wetting. The research was designed as a cross-sectional study. Vaginal dryness was assessed by scores in the lubrication domain of the Female Sexual Function Index (FSFI) questionnaire and the Vaginal Maturation Index (VMI) determined by vaginal hormonal cytology, as well as the measurement of vaginal lubrication using Schirmer strips placed at the anterior vaginal wall. Medians (25th-75th percentiles) were calculated for each group and compared using a nonparametric Kruskal-Wallis test and the Dunn-Bonferroni post hoc method. Outcomes were detection of the presence of vaginal dryness in women who were infected or noninfected with HTLV-1. HTLV-1-infected women (n = 72, 57 asymptomatic and 15 with HTLV-1-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) and uninfected women (n = 49) were studied. Women with HAM/TSP had significantly lower FSFI lubrication scores than asymptomatic and uninfected women (P = .032). In addition, women with HAM/TSP had significantly lower VMI compared with the asymptomatic and uninfected groups (P = .027 and P = .039, respectively). The results of this study show a reduction in vaginal lubrication in HTLV-1-infected women diagnosed with HAM/TSP compared with asymptomatic and uninfected women. The lack of a gold standard test for the diagnosis of vaginal dryness and the fact that no assessment of vaginal pH was performed were limitations of this study. The strength of the study was the comprehensive assessment of vaginal dryness from several perspectives: subjective (perception of vaginal lubrication according to the vaginal lubrication domain of the FSFI), hormonal (vaginal hormonal cytology to assess local hormone status), and the degree of vaginal moisture (direct measurement of vaginal dryness with an instrument, the Schirmer strip, already used to measure the presence of dry eye). HTLV-1-infected women with HAM/TSP have decreased vaginal lubrication compared with asymptomatic and uninfected women after adjusting for age.

CXCL9, 10, 11/CXCR3 Axis Contributes to the Progress of Primary Sjogren's Syndrome by Activating GRK2 to Promote T Lymphocyte Migration.

Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that causes dysfunction of secretory glands and the specific pathogenesis is still unknown. The CXCL9, 10, 11/CXCR3 axis and G protein-coupled receptor kinase 2 (GRK2) involved in many inflammation and immunity processes. We used NOD/Ltj mice, a spontaneous SS animal model, to elucidate the pathological mechanism of CXCL9, 10, 11/CXCR3 axis promoting T lymphocyte migration by activating GRK2 in pSS. We found that CD4 + GRK2, Th17 + CXCR3 was apparently increased and Treg + CXCR3 was significantly decreased in the spleen of 4W NOD mice without sicca symptom compared to ICR mice (control group). The protein levels of IFN-γ, CXCL9, 10, 11 increased in submandibular gland (SG) tissue accompanied by obvious lymphocytic infiltration and Th17 cells overwhelmingly infiltrated relative to Treg cells at the sicca symptom occurs, and we found that the proportion of Th17 cells was increased, whereas that of Treg cells was decreased in spleen. In vitro, we used IFN-γ to stimulate human salivary gland epithelial cells (HSGECs) co-cultured with Jurkat cells, and the results showed that CXCL9, 10, 11 was increased by IFN-γ activating JAK2/STAT1 signal pathway and Jurkat cell migration increased with the raised of cell membrane GRK2 expression. HSGECs with tofacitinib or Jurkat cells with GRK2 siRNA can reduce the migration of Jurkat cells. The results indicate that CXCL9, 10, 11 significantly increased in SG tissue through IFN-γ stimulating HSGECs, and the CXCL9, 10, 11/CXCR3 axis contributes to the progress of pSS by activating GRK2 to promote T lymphocyte migration.

Sjogren's Syndrome: Multidisciplinary Approach to Diagnosis and Management

Purpose: Sjögren’s syndrome (SS) is a chronic and progressive multisystem autoimmune disease typically managed by rheumatologists. Diagnostic delays are common, due in large part to the non-specific and variable nature of SS symptoms and the slow progression of disease.
 Methodology: This article reviews current understanding of the clinical manifestations, diagnosis and treatment of Sjögren's syndrome and its attendant ocular manifestation. Sjögren's syndrome is a chronic inflammatory disorder of the exocrine glands with multiple non exocrine features. It is found predominantly in middle-aged women but exists throughout the population. The diagnosis of Sjögren's syndrome can be challenging because the cardinal sicca symptoms may be subclinical or attributed to other causes, such as medications or aging. Differential diagnosis of Sjögren's syndrome can be confounded by the multiple exocrine manifestations in the mouth, eyes, ears, nose, skin, vagina, and respiratory and gastrointestinal tracts. Characteristics of SS are dry eye and dry mouth, which are typically the earliest presenting complaints, eye care clinicians such as the optometrists and dental professionals are often the first point of medical contact and can provide critical collaboration with rheumatologists to facilitate both timely diagnosis and ongoing care of patients with SS.
 Findings: Current diagnostic criteria advocated by the American College of Rheumatology are predicated on the presence of signs/symptoms suggestive of SS along with at least two objective factors such as traditional biomarker positivity, salivary gland biopsy findings, and/or presence of keratoconjunctivitis sicca. Timely diagnosis of SS requires appropriate clinical vigilance for potential SS symptoms, referral and collaborative communication among rheumatology, optometrists, ophthalmology, and oral care professions.
 Unique Contribution to Theory, Practice and Policy: It is concluded that optometrists can now identify Sjogren’s patients earlier in their dry eye population with a new advanced diagnostic test Sjo,the laboratory test designed for early detection of Sjogren’s syndrome, has been available from Nicox for use by eye care professionals since November,2013. Optometrists have a role to play in the management of ocular manifestations of Sjogren’s syndrome. Such symptoms can lead to discomfort, blurred vision, and visual fatigue if not attended to immediately.
 For people with immune system disorder, inflammation of tear-secreting glands reduces tear production, resulting in chronic dry eyes. Prescription eye drops such as Tears Naturale, Cyclosporine (Restasis) or Lifetegrast(Xiidra) may be recommended by the eye doctor if you have moderate to severe dry eyes.

Melatonin: a potential therapeutic approach for the management of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that primarily affects the exocrine glands and is mainly characterized by sicca symptoms of the eyes and mouth. Approximately 30-50% of pSS patients develop systemic multi-organ disorders including malignant lymphoma. The etiology of pSS is not well understood; growing evidence suggests that uncontrolled immune/inflammatory responses, excessive oxidative stress, defected apoptosis, dysregulated autophagy, exosomes, and exogenous virus infections may participate in the pathogenesis of pSS. There is no ideal therapeutic method for pSS; the management of pSS is mainly palliative, which aims to alleviate sicca symptoms. Melatonin, as the main secretory product of the pineal gland, has been evidenced to show various physiological functions, including effects of immunoregulation, capability of antioxidation, moderation of autophagy, suppressive activities of apoptosis, regulative capacity of exosomes, properties of anti-infection, and improvement of sleep. The beneficial effects of melatonin have been already validated in some autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). However, our previous research firstly revealed that melatonin might inhibit pathogenic responses of peripheral Th17 and double-negative (DN) T cells in pSS. More importantly, melatonin administration alleviated the development of pSS in animal models with reduced infiltrating lymphocytes, improved functional activity of salivary gland, and decreased production of inflammatory factors as well as autoantibodies. Owing to the important biological properties reported in melatonin are characteristics closely related to the treatment of pSS; the potential role and underlying mechanisms of melatonin in the administration of pSS are certainly worth further investigations. Consequently, the aim of this review is to give a deep insight to the therapeutic potency of melatonin for pSS.

Sjogren’s Syndrome: An Ocular Overview

Sjogren’s syndrome (SS) is a chronic systemic autoimmune disorder which predominantly affects the salivary and lacrimal glands (exocrine glands) resulting in presentation of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia), collectively known as sicca symptoms. Although ren SS primarily affects glands, in some cases there is extra-glandular involvement indicating an autoimmune response can occur in other organs and tissues. SS is categorised into primary, when symptoms occur in isolation, or secondary, when symptoms occur in conjunction with another autoimmune disorder such as rheumatoid arthritis or systemic lupus erythematosus.

New aspects of clinical and immunological characteristics in patients with anti-asparaginyl tRNA synthetase (anti-KS) autoantibody.

Anti-asparaginyl tRNA synthetase (anti-KS) antibody is present in patients with interstitial lung disease (ILD) accompanied by polymyositis/dermatomyositis. We examined clinical/immunological features of these patients. Polymyositis/dermatomyositis or ILD patients were screened for autoantibodies, and clinical/immunological data were collected retrospectively. ILD was diagnosed by computed tomography, and clinical/immunological features of anti-KS-positive patients were compared with those of anti-Jo-1-positive patients. Sixteen anti-KS-positive patients [female = 11; male = 5; average age 63.6 years (range, 40-81) years] were diagnosed: seven had ILD, four had clinically amyopathic DM (CADM) and ILD, three had Sjögren's syndrome (SS) and ILD one each had rheumatoid arthritis and ILD, or CADM/SS overlap and ILD. All patients had ILD with chronic onset and clinical course; 11/16 (69%) had nonspecific interstitial pneumonia, and five (31%) had usual interstitial pneumonia pattern. Regarding skin manifestations, 4 (27%) had typical DM rash and 11 (69%) had mechanic's hands. All anti-KS-positive patients had no clinical muscle weakness or serum creatine kinase elevation; 8/16 patients (50%) had sicca symptoms at a significantly high frequency compared with anti-Jo-1-positive patients (50% vs 11%, P = 0.01). Anti-KS-positive patients might form a distinguishable subset closely associated with sicca symptoms, CADM and chronic-type ILD with a relatively favourable prognosis.

Time-Dependent Analysis of Sicca Symptoms and Anti-Ro/SSA and Anti-La/SSB Antibodies in Patients with AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and Sjögren syndrome (SS) are likely comorbidities. However, the exact effects of age and disease duration on the positivity rates of serum anti-Ro/SSA and anti-La/SSB (anti-SSA/SSB) antibodies and the presence of sicca symptoms in patients with AQP4-IgG remain unknown. In the present study, we evaluated the data from patients with suspected NMOSD who had neurological episodes and tested for serum AQP4-IgG. Associations between the presence of serum AQP4-IgG and SS-related findings were evaluated. The presence of anti-SSA/SSB antibodies [odds ratio (OR), 7.34; 95% confidence interval (CI), 5.71-9.43; p < 0.0001] and that of sicca symptoms (OR, 2.08; 95% CI, 1.67-2.58; p < 0.0001) were both higher in patients with AQP4-IgG (n = 1,651) than in those without AQP4-IgG (n = 2,796). Meanwhile, neither age nor the elapsed time from neurological onset was linked to the prevalence of anti-SSA/SSB antibodies or sicca symptoms, and the prevalence rates of the SS-related factors were elevated since the onset of neurological episodes in those with AQP4-IgG. The frequency of sicca symptoms among those with anti-SSA/SSB antibodies was irrespective of AQP4-IgG (OR, 1.11; 95% CI, 0.67-1.85; p = 0.6892). The measured AQP4-IgG titers did not differ significantly according to the presence of anti-SSA/SSB antibodies (p = 0.2386; Mann-Whitney U test). In summary, age and duration of NMOSD were not the factors producing an elevated prevalence of anti-SSA/SSB antibodies and sicca symptoms in patients with AQP4-IgG, implying that the occurrence of comorbid SS is likely to temporarily precede or synchronize with the onset of AQP4-IgG-positive NMOSD.

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series

BackgroundThe majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease. Aims and methodsTo retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland. ResultsIn all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time. ConclusionsBelimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

Primary Sjögren’s syndrome with renal tubular acidosis and central pontine myelinolysis: An unusual triad

Primary Sjögren's syndrome (pSS) is a complex, multisystem autoimmune disorder. It is characterized by lymphocytic infiltration of the exocrine glands. In the setting of pSS, the presence of systemic disease is an important prognostic determinant, but involvement of the kidney is uncommon. The triad of pSS, distal renal tubular acidosis (dRTA), and central pontine myelinolysis (CPM) is rare and potentially fatal. A 42-year-old woman presented with dRTA, profound hypokalemia, and CPM characterized by progressive global quadriparesis, ophthalmoplegia, and encephalopathy. Sjögren's syndrome was diagnosed based on sicca symptoms, clinical features, and strongly positive anti-SSA/Ro and anti-SSB/La autoantibodies. The patient responded well to electrolyte replacement, acid-base correction, corticosteroids, and subsequent cyclophosphamide therapy. Early recognition and appropriate treatment resulted in good kidney and neurological outcomes in this case. This report highlights the need to consider the diagnosis of pSS in unexplained dRTA and CPM, as it has a favorable prognosis if recognized and managed timeously.

Ocular surface changes before and after upper eye lid blepharoplasty

Background: Blepharoplasty has been the most effective treatment for upper eyelid dermatochalasis. Dry eye disease after blepharoplasty can only be detected after sufficient time to allow for resolution of the early and intermediate sicca symptoms. Aim of work: studying the ocular surface changes before and after upper eyelid blepharoplasty.Patients and methods: our prospective interventional cohort study conducted on 30 patients, (aged between 40 and 60 years) underwent upper eye lid blepharoplasty. Results: The included 30 subjects were females only aged from 40 years to 60 years with the Mean ± standard deviation were 51.07±4.93 years. The values of tear meniscus height, depth, and cross-section area decreased significantly at 1 month postoperatively, then started to increase after 3 months postoperative and returned like preoperative after 6 months.Conclusion: Upper eye lid blepharoplasty can affect the ocular surface and tear film stability. The values of tear meniscus height, depth, and cross-section area and dry eye tests except the ocular surface staining decreased significantly at 1 month postoperatively, then started to increase after 3 months postoperative and returned like preoperative after 6 months.

Efficacy of cyclosporine eyedrop 0.1% in the treatment of dry eye in primary sjogren's syndrome: A prospective Indian study

Objectives: The objective of this study was to evaluate the efficacy and safety of 0.1% cyclosporine A (CsA) eyedrop in patients having primary Sjogren's syndrome (SS) in India. Methods: A prospective consecutive case series of total 20 patients with moderate-to-severe dry eyes were treated with 0.1% CsA eyedrop twice daily along with lubricating eyedrop for 3 months. Efficacy measures included ocular staining score (OSS), van Bijsterveld score (VBS), and Schirmer's score of each eye based on the 2016 ACR-EULAR classification. Subjective improvement was also recorded at the final visit. Any adverse effects were noted. Results: Treatment with 0.1% CsA eyedrop showed a statistically significant improvement at 3 months for both OSS and VBS in each eye of study patients. A similar improvement in Schirmer's score was noted in each eye of the subjects. Subjective improvement of ocular sicca symptoms was also demonstrated. There was excellent compliance to therapy. The 0.1% CsA formulation did not show any topical or systemic side effects in any patient. Conclusion: The 0.1% ophthalmic preparation of CsA is safe and effective in the management of moderate-to-severe dry eyes in patients with primary SS in this pilot study in Indian patients.

Central Nervous System Involvement in Primary Sjögren’s Syndrome: Narrative Review of MRI Findings

Central nervous system (CNS) involvement is one of the numerous extraglandular manifestations of primary Sjögren's syndrome (pSS). Moreover, neurological complaints precede the sicca symptoms in 25-60% of the cases. We review the magnetic resonance imaging (MRI) lesions typical for pSS, involving the conventional examination, volumetric and morphometric studies, diffusion tensor imaging (DTI) and resting-state fMRI. The most common radiological lesions in pSS are white matter hyperintensities (WMH), scattered alterations hyperlucent on T2 and FLAIR sequences, typically located periventricularly and subcortically. Cortical atrophy and ventricular dilatation can also occur in pSS. Whilst these conditions are thought to be more common in pSS than healthy controls, DTI and resting-state fMRI alterations demonstrate evident microstructural changes in pSS. As pSS is often accompanied by cognitive symptoms, these MRI alterations are expectedly related to them. This relationship is not clearly delineated in conventional MRI studies, but DTI and resting-state fMRI examinations show more convincing correlations. In conclusion, the CNS manifestations of pSS do not follow a certain pattern. As the link between the MRI lesions and clinical manifestations is not well established, more studies involving larger populations should be performed to elucidate the correlations.

Determinants of health-related quality of life across the spectrum of connective tissue diseases using latent profile analysis: results from the LEAP cohort.

Poor health-related quality of life (HRQoL) is well recognized in patients with CTD. We hypothesized that subgroups of patients across the spectrum of CTD experience different HRQoL patterns and aimed to determine patient-level characteristics associated with these different subgroups. Using the eight continuous domains of the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire we performed data-driven clustering to derive latent profiles (LPs) of patients with distinct HRQoL patterns. Multivariable ordinal logistic regression was used to determine patient-level characteristics associated with each HRQoL subgroup identified. A total of 309 CTD patients completed the SF-36 questionnaire. The most impaired SF-36 domains in each disease group were vitality, general health and bodily pain. The physical component of the SF-36 was consistently more impaired compared with the mental component, with similar scores across disease groups. Three LPs were identified with poor [n = 89 (29%)], average [n = 190 (61.4%)] and excellent [n = 30 (9.7%)] HRQoL. LPs were not associated with diagnostic grouping or autoantibody profiles. Black background [odds ratio (OR) 0.22 (95% CI 0.08, 0.63)], Indo-Asian background [OR 0.39 (95% CI 0.19, 0.78)], concomitant fibromyalgia [OR 0.40 (95% CI 0.20, 0.78)], sicca symptoms [OR 0.56 (95% CI 0.32, 0.98)] and multimorbidity [Charlson Comorbidity Index; OR 0.81 (95% CI 0.67, 0.97)] were associated with the 'poor' HRQoL LP. Distinct HRQoL subgroups exist that are not primarily driven by a specific diagnosis or autoantibody profiles. We identified a number of key demographic and clinical factors associated with poor HRQoL. These factors need to be addressed across the whole CTD spectrum as part of a holistic management approach aimed at improving overall patient outcomes.

Sjogren’s Sensory Neuropathy: A Potentially Treatable Condition with Early Intervention

Objective To describe 2 cases of Sjögren's syndrome sensory neuronopathy (SSSN) in which early intervention resulted in excellent clinical outcomes. Background Acquired sensory neuronopathies (i.e. dorsal root ganglionopathies) are rare sensory neuropathies most commonly associated with Sjögren's syndrome (SS) and paraneoplastic syndromes. Design/Methods We describe 2 patients who presented with painful sensory symptoms, sicca symptoms and with positive SSA and antinuclear antibodies. The first patient presented with perceived symmetric hand weakness (despite no motor nerve conduction abnormalities), total body numbness and paresthesia, as well as sensory ataxia, while the other presented with asymmetric numbness and pain in the left foot and hand. The electrophysiological profiles varied considerably between the 2 patients. The first patient demonstrated complete absence of sensory nerve action potentials (SNAPs) whereas the second patient had only asymmetrical superficial peroneal and sural SNAPs, corresponding with his clinical deficit. The first patient was diagnosed with SSSN, while the other was diagnosed with asymmetrical sensory neuropathy in SS. The first patient was treated with mycophenolate mofetil (MMF) with dramatic symptomatic improvement and near recovery of clinical deficits. The second patient was treated with prednisone, methotrexate, and ultimately switched to MMF and rituximab with significant improvement in symptoms. Results NA. Conclusions SS is commonly associated with sensory neuropathies including sensory neuronopathies. Both patients met diagnostic criteria for SSSN, though with differing severities. To date, there has been no randomized controlled trial evaluating treatments of SSSN. However, our findings suggest that early use of MMF could result in considerable benefit in a disease that is often functionally devastating.

Association Between Vitamin D and Minor Salivary Gland Inflammation.

Objective There has been increasing research regarding the effects of vitamin D on autoimmune disorders. There is some evidence of a correlation between vitamin D levels and sicca symptoms. We attempted to evaluate the correlation between vitamin D levels and inflammation of the minor salivary gland (MSG). Methods Data for 214 patients who had undergone MSG biopsy were reviewed. Eighteen patients with other autoimmune/neoplastic processes were excluded. Seventy-seven of 196 patients had serum Vitamin D levels available and were selected for this retrospective study. Demographic, clinical, and immunological features, extra-glandular manifestations, autoantibodies, and clinical laboratory tests were collected and compared between patient groups with a focus score (FS) of 0 and 1 or more. Results Out of 77, 29 patients had an FS of 0 while 48 had an FS of 1 or more. Mean vitamin D levels were noted to be lower in patients with an FS of 1 when compared to patients with an FS of 1 or more. Conclusion In this study, patients with an FS of 1 were noted to have low vitamin D levels but this association was not seen at a higher FS.

Comprehensive analysis of clinical and laboratory features of 440 published cases of Sjögren's syndrome and renal tubular acidosis.

To describe the clinical and laboratory features of Sjögren's syndrome (SS) with renal tubular acidosis (RTA) from published literature. A systematic search of indexed publications in all languages till December 2021 identified cases of SS with RTA (SS-RTA) and were included if either antibody (anti-SSA/anti-SSB) or salivary gland histopathology were positive. There were 440 cases of SS-RTA (63.9% from Asia, 95.5% women). The median (range) age was 37 (6-78) years. Only 7.7% had a previous diagnosis of SS. Oral or ocular sicca symptoms were present in 63.7%. Positive ocular tests, oral tests, anti-SSA, anti-SSB and salivary gland histopathology were reported in 256/331 (77.3%), 123/128 (96%), 382/407 (93.9%), 298/379 (78.6%), and 246/268 (91.8%), respectively. Hypokalemic paralysis (HP) was the presenting feature in 63.6%; 25% had multiple episodes of HP and 8.4% had respiratory paralysis. Type 1, type 2, combined type 1 & 2, and type 4 RTA was seen in 388, 8, 38, and 3 patients, respectively. Proximal dysfunction and RTA complications were infrequently evaluated. Fanconi syndrome, nephrogenic diabetes insipidus, proteinuria, and low estimated glomerular filtration rate were found in 45, 21, 178, and 157, respectively. Nephrocalcinosis, renal stones, and osteomalacia were reported in 92, 79, and 72, respectively. Tubulointerstitial nephritis was found in 142 out of 152 renal biopsies. SS-RTA is an early manifestation of SS characterized by younger age and subclinical sicca symptoms. Although evaluated less frequently, oral sicca signs and salivary gland biopsy have a high positive yield. HP is the most common presentation. RTA is mostly distal; proximal dysfunction and complications were infrequently assessed.

Histological evolution of IgG4 related disease

Histological evolution of IgG4 related disease

How Are Sicca Signs and Symptoms Associated With Depression Among Men Classified With and Without Sjögren Disease?

Sjögren disease (SjD) cohorts represent rich resources to study associations between dry eye/mouth (sicca) signs/symptoms and depression. Because SjD affects mainly women, little is known about men with sicca signs/symptoms and associations with depression. The Sjögren's International Collaborative Clinical Alliance contained many men allowing for studying associations between sicca signs/symptoms and depression. We hypothesized that sicca symptoms would be positively associated with depression in males. Cross-sectional study. At baseline, participants completed questionnaires and underwent ocular and oral examinations. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression models were used to identify associations between depression and SjD diagnostic criteria and sicca symptoms. Of 309 males, 98 were classified as SjD, whereas 198 were classified as non-SjD. We found that having a labial salivary gland biopsy with focus score ≥1 foci/mm2 was associated with a lower odds of being classified as depressed (odds ratio [OR]: 0.36, 95% CI: 0.18-0.73, P=.01). Having positive anti-Sjögren syndrome antigen A antibody was associated with lower odds of being classified as depressed (OR: 0.44, 95% CI: 0.23-0.88, P=.02). Higher odds of depression were found with ocular burning (OR: 3.16, 95% CI: 1.74-5.73, P < .001), light sensitivity (OR: 2.59, 95% CI: 1.48-4.55, P=.001), and complaints of dry mouth (OR: 4.58, 95% CI: 1.54-13.63, P=.006). Ophthalmologists should be specific when inquiring about ocular discomfort (focusing on burning and light sensitivity) and consider querying about depression and/or providing mental health resources to those who endorse such qualities.

Saliva Free Light Chains in Patients with Neuro-Sjögren.

Background: Sjögren’s syndrome (SS) is an autoimmune disease characterized by sicca symptoms and various extra-glandular manifestations. The diagnosis of SS requires sicca symptoms, anti-SSA(Ro)-antibody positivity, and/or pathological focus scores on a minor salivary gland biopsy. Previous studies have investigated different biomarkers in order to avoid invasive diagnostic procedures. It was found that kappa and lambda free light chains (KFLC and LFLC) in saliva are specific for SS. Methods: FLC concentrations in saliva and serum were determined in 130 patients—50 with SS and neurological involvement (Neuro-Sjögren) and 80 neurological controls. The EULAR SS disease activity index and patient reported index (ESSPRI) were determined in patients with SS. Results: Patients with SS revealed increased pain and decreased saliva production according to the ESSPRI and Saxon test, respectively, with increasing FLC concentrations in the saliva. No significant differences in serum and salivary protein concentrations were observed between patients with SS and controls. Conclusion: KFLC and LFLC concentrations in saliva are not suitable to distinguish patients with Neuro-Sjögren and neurological control subjects, thus a diagnostic biopsy is still required. The association of salivary KFLC and LFLC concentrations with saliva production and ESSPRI pain score suggests a complex relationship between dryness and pain in patients with SS.