Sjögren’s syndrome (2nd most common rheumatic disease) and vitamin D

Dry eye more severe with lower vitamin D in Sjögren Syndrome - Dec 2019

The Association of Serum Vitamin D Level With the Severity of Dry Eye Parameters in Primary Sjögren Syndrome
Cornea. 2019 Dec 20. doi: 10.1097/ICO.0000000000002234.
Lee JH1, Kim SJ2, Byun YS2, Lee J3, Park SH3, Chung SH2.

PURPOSE: To analyze the relationship between serum 25(OH)D3 level and dry eye parameters in primary Sjögren syndrome (SS).

METHODS: This study included 74 eyes of 74 patients diagnosed with primary SS. Dry eye parameters included tear breakup time, Schirmer I value, corneal staining score, conjunctival staining score, and Ocular Surface Disease Index. The serum concentration of 25(OH)D3 was evaluated.

RESULTS:
The mean serum 25(OH)D3 level was 20.4 ± 8.0 ng/mL.
There were strong negative correlations between serum 25(OH)D3 level and corneal staining score (P < 0.001, r = -0.446) and conjunctival staining score (P < 0.001, r = -0.455).
The Schirmer I value and tear breakup time showed significant positive correlations with serum 25(OH)D3 level (P = 0.038, r = 0.261 and P = 0.003, r = 0.352, respectively).
The Ocular Surface Disease Index did not show any significant correlation with serum 25(OH)D3 level.

CONCLUSIONS: This study demonstrates that serum 25(OH)D3 level might be associated with dry eye severity in primary SS.

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Vitamin D and Sjögren syndrome - Review April 2017

Autoimmunity Reviews, Available online 12 April 2017, http://doi.org/10.1016/j.autrev.2017.04.004
Mario Garcia-Carrascoa, b, Erick Alejandro Jiménez-Herreraa, Jose Luis Gálvez-Romeroc, Luis Vázquez de Larad, Claudia Mendoza-Pintoa, b, Ivet Etchegaray-Moralesa, Pamela Munguía-Realpozoe,

Highlights
• Vitamin D immunomodulatory functions could be benefit in autoimmune diseases.
• Vitamin D deficiency has been reported in patients with Sjögren syndrome.
• UV radiation and vitamin D could interact with the Sjögren syndrome pathogenesis.
• Vitamin D low levels are associated to extraglandular manifestations.

The immunomodulatory effects of vitamin D have been extensively studied in the context of autoimmunity. Multiple studies have demonstrated a high prevalence of vitamin D deficiency in autoimmune diseases. Recently, a possible protective role of vitamin D in autoimmunity has been described; however, this function remains controversial. Few studies have investigated the role of vitamin D in patients with Sjögren syndrome (SS). In this review, we compiled the main features of SS pathogenesis, the vitamin D immunomodulatory effects and the possible interaction between both. Data suggests that vitamin D may play a role in the SS pathogenesis. In addition, vitamin D low levels have been found in SS patients, which are associated with extra-glandular manifestations, such as lymphoma or neuropathy, suggesting a possible benefit effect of vitamin D in SS.

Abbreviations APC, Antigen-presenting cell; BAFF, B-cell activating factor; DBP, vitamin D-binding protein; EBV, Epstein-Barr virus; RA, Rheumatoid arthritis; SLE, Systemic lupus erythematosus; SS, Sjögren syndrome; Treg, T regulatory cell; VDR, Vitamin D receptor; VDRE, Vitamin D response element
Publisher wants $32 for the PDF

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Novel aspects of Sjögren’s syndrome in 2012

BMC Medicine 2013, 11:93 doi:10.1186/1741-7015-11-93
Angela Tincani 1,2*, Laura Andreoli 2, Ilaria Cavazzana 1, Andrea Doria 3, Marta Favero 3, Maria-Giulia Fenini 4, Franco Franceschini 1, Andrea Lojacono 5, Giuseppe Nascimbeni 6, Amerigo Santoro 7, Francesco Semeraro 6, Paola Toniati1 and Yehuda Shoenfeld 8 * *Corresponding author: Angela Tincani tincani at med.unibs.it
1 Rheumatology and Clinical Immunology Unit, Spedali Civili, Piazzale Spedali Civili 1, 25100 Brescia, Italy
2 Chair of Rheumatology, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili, Piazzale Spedali Civili 1, 25100 Brescia, Italy
3 Rheumatology Unit, Department of Medicine, University of Padua, Azienda Ospedaliera di Padova, Via Giustiniani 2, Padua, 35128, Italy
4 Rheumatology Unit, Vallecamonica Hospital, Via Manzoni 142, Esine (Brescia), 25040, Italy
5 Obstetrics and Gynecology Unit, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, Brescia, 25100, Italy
6 Ophthalmology Unit, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, Brescia, 25100, Italy
7 Pathology Unit, Spedali Civili, Piazzale Spedali Civili 1, Brescia, 25100, Italy
8 Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Hashomer, 52621, Israel
Received: 19 November 2012; Accepted: 15 February 2013; Published: 4 April 2013

Sjögren’s syndrome (SS) is a systemic progressive autoimmune disease characterized by a complex pathogenesis requiring a predisposing genetic background and involving immune cell activation and autoantibody production. The immune response is directed to the exocrine glands, causing the typical ‘sicca syndrome’, but major organ involvement is also often seen. The etiology of the disease is unknown. Infections could play a pivotal role: compared to normal subjects, patients with SS displayed higher titers of anti-Epstein-Barr virus (EBV) early antigens, but lower titers of other infectious agent antibodies such as rubella and cytomegalovirus (CMV) suggest that some infections may have a protective role against the development of autoimmune disease. Recent findings seem to show that low vitamin D levels in patients with SS could be associated with severe complications such as lymphoma and peripheral neuropathy. This could open new insights into the disease etiology. The current treatments for SS range from symptomatic therapies to systemic immunosuppressive drugs, especially B cell-targeted drugs in cases of organ involvement. Vitamin D supplementation may be an additional tool for optimization of SS treatment.

PDF is attached at the bottom of this page

Sections on vitamin D clipped from the PDF

Novel aspects of SS: the role of infections and vitamin D Infections and SS

The etiology of autoimmune diseases (AID) is multifactorial where genetic, immunologic, hormonal and environmental factors play in concert in their induction. The final step determining the date of emergence of an AID is most probably an environmental trigger, which is generally of infectious origin [73]. In the interplay between infectious agents and autoimmunity it was found that the same infectious agent (that is, Epstein-Barr Virus (EBV)) may be involved in inducing many autoimmune diseases, while the same autoimmune disease may be caused by various agents (that is, EBV, cytomegalovirus (CMV), Helicobacter pylori, and so on) [74].
Recently, several multicenter studies analyzed a large number of sera samples (>2,500) from patients with AID such as SS, SLE, antiphospholipid syndrome (APS), RA, vasculitides, and others for the presence of a profile of anti-infectious agents antibodies including EBV, CMV, H. pylori,rubella,treponema,Herpesvirus and toxoplasmosis. In several diseases a higher prevalence and titers of anti-infectious antibodies were found compared with healthy controls matched for sex, age and ethnicity [75-80]. For instance, in patients with SS the prevalence and titers of antibodies against EBV-early antigen were significantly higher than in their control group (P = 0.0003).

Interestingly, in some diseases lower titers of anti-infectious agents were found, such as the lower prevalence and titers of rubella and CMV antibodies (IgM) detected in patients with SS compared to controls (P <0.02). This may allude indirectly to the notion that some infectious agents may have a protective rather thanapathogenicrole for a specific autoimmune disease.
Furthermore, a certain infectious agent may determine why an individual with the 'proper' genetic background will develop one AID rather than others, as well as its clinical manifestations and severity.

Low levels of vitamin D are associated with neuropathy and lymphoma among patients with SS

The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin D, may play a role in the pathogenic process and disease expression.
The levels of vitamin D and their association with manifestations of SS were studied in a large international multicenter cohort [81]. Vitamin D levels were determined in 176 patients with pSS and 163 matched healthy volunteers utilizing LIAISON chemiluminescent immunoassays (DiaSorin, Saluggia, Italy). Mean vitamin D levels were comparable between patients with SS and controls: 21.2 ± 9.4 ng/ml and 22.4 ± 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of patients with SS and associated with lower vitamin D levels (18.6 ±5.5 ng/ml vs 22.6 ± 8 ng/ml (P =0.04)). Lymphoma was diagnosed in 4.3% of patients with SS, who had lower levels of vitamin D, 13.2 ± 6.25 ng/ml, compared to patients with SS without lymphoma (22 ± 8 ng/ml; P= 0.03). Other clinical and serological manifestations did not correlate with vitamin D status.

This study reported for the first time the presence of low vitamin D levels in patients with pSS with peripheral neuropathy.
Overall, it seems that vitamin D deficiency may be a component in the pathogenesis of neuropathy in pSS, and may be used for monitoring and treatment of this condition [82-87].

Patients with pSS are at increased risk for NH lymphoma compared to healthy populations [44]. While the relationship between vitamin D and the risk for lymphoma in pSS has not been reported previously, there is some evidence from case-control studies that low dietary intake of vitamin D is associated with an increased risk for NHL in the normal population [88,89]. Vitamin D and its metabolites have been shown to have an antiproliferative effect on lymphoma cell lines and to attenuate their vitamin D receptor (VDR) expression [90].

Thus, low vitamin D levels may join low complements components and the presence of cryoglobulins in predicting eventual development of lymphoma in patients with SS.

Given the associations between hypovitaminosis D and severe complications of SS, it can be proposed that vitamin D supplementation should be given to every patient with SS.

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Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjögren's syndrome.

J Autoimmun. 2012 Sep;39(3):234-9. doi: 10.1016/j.jaut.2012.05.018. Epub 2012 Jul 24.
Agmon-Levin N, Kivity S, Tzioufas AG, López Hoyos M, Rozman B, Efes I, Shapira Y, Shamis A, Amital H, Youinou P, Shoenfeld Y.
The Zabludowicz Center for Autoimmune Diseases, The Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.

BACKGROUND/PURPOSE: Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin-D may play a role in the pathogenic process and disease expression. Thus, we aimed to evaluate levels of vitamin-D and their association with manifestations of SS.

METHODS: Vitamin-D levels were determined in 176 primary SS patients and 163 matched healthy volunteers utilizing the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). A correlation between vitamin-D levels and clinical and serological manifestations of SS was performed.

RESULTS: Mean vitamin-D levels were comparable between SS patients and control 21.2 ± 9.4 ng/ml and 22.4 ± 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of SS patients and associated with lower vitamin-D levels (18.6 ± 5.5 ng/ml vs. 22.6±8 ng/ml (p = 0.04)). Lymphoma was diagnosed in 4.3% of SS patients, who had lower levels of vitamin-D (13.2 ± 6.25 ng/ml), compared to SS patients without lymphoma (22 ± 8 ng/ml), (p = 0.03). Other clinical and serological manifestations did not correlate with vitamin-D status.

CONCLUSIONS: In this study, low levels of vitamin-D correlated with the presence of peripheral neuropathy and lymphoma among SS patients. The link between vitamin-D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin-D in the pathogenesis of these processes. Plausible beneficial effect for vitamin-D supplementation may thus be suggested.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22835660

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Primary Sjögren's syndrome and malignancy risk: a systematic review and meta-analysis {Vit D not mentioned in abstract}

Ann Rheum Dis doi:10.1136/annrheumdis-2013-203305, Clinical and epidemiological research
Yan Liang, Zaixing Yang, Baodong Qin, Renqian Zhong
Department of Laboratory Diagnostics, Changzheng Hospital, Second Military Medical University, Shanghai, China
Correspondence to Dr Yang Zaixing and Professor Renqian Zhong, Department of Laboratory Diagnostics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China; yangzaixingdiyi at 163.com and rqzhong at yahoo.com
Accepted 14 April 2013, Published Online First 17 May 2013

Objective To investigate the association between primary Sjögren's syndrome (pSS) and the risks of malignancy including overall malignancy and site-specific malignancies through a systematic review and meta-analysis.

Methods We searched Pubmed before January 2013, with a restriction to English language publications. Studies were included if they met the following criteria: (1) a cohort or observational study; (2) pSS as one of the exposure interests; (3) cancer as an outcome of interest; (4) relative risk (RR) or standardised incidence rate (SIR) with 95% CIs. We used a random or fixed effects model to calculate the pooled RR according to the heterogeneity test.

Results Fourteen studies involving more than 14 523 patients with pSS were included. Compared with the general population, patients with pSS had
significantly increased risks of

• overall cancer (pooled RR 1.53; 95% CI 1.17 to 1.88),
• non-Hodgkin lymphoma (NHL) (pooled RR 13.76; 95% CI 8.53 to 18.99) and
• thyroid cancer (pooled RR 2.58; 95% CI 1.14 to 4.03).

A significant association was found in various subgroup meta-analyses for NHL but, for overall malignancy, a significant association was only found in some groups.
Additionally, the number of studies exploring the association of pSS with the risk of solid malignancies was so small that we could not carry out subgroup meta-analyses.

Conclusions This meta-analysis indicates that pSS is significantly associated with increased risks of overall malignancy, NHL and thyroid cancer.
However, it is not yet known whether the apparent increased risk of overall malignancy in patients with pSS is due to the relatively high prevalence of NHL in that group.

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Clips from Wikipedia April 2013

Nine out of ten Sjögren's patients are women[4][5] and the average age of onset is after menopause in women, although Sjögren's occurs in all age groups in both women and men.

It is estimated to affect as many as 4 million people in the United States alone, making it the second most common rheumatic disease.

The hallmark symptom of Sjögren's syndrome is a generalized dryness, typically including xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), part of what are known as sicca symptoms.

In addition, Sjögren's syndrome may cause skin, nose, and vaginal dryness, and may affect other organs of the body, including the kidneys, blood vessels, lungs, liver, pancreas, peripheral nervous system (distal axonal sensorimotor neuropathy) and brain.

The overall prevalence of Sjögren’s Syndrome is estimated to be between 0.2 and 0.65% of the total population.

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Mega Doses Of Vitamin D reduces Sjögren’s fatigue for one person

SjoDry’s Drag Race Sep 2015
Does not state how much was used
Includes the following description
A chronic, slowly progressive autoimmune disease that affects the “exocrine” (moisture producing) glands of the body. It is classified as a “connective tissue disease.” Some other types of connective tissue diseases are: Lupus, Scleroderma, and Rheumatoid Arthritis. Ninety percent of those afflicted with SS are women. Sjogrens can accompany other autoimmune diseases, most frequently seen in conjunction with Rheumatoid Arthritis. When it is found with another connective tissue disease, it is called “secondary sjs.”

Sjogren’s Syndrome is classified as “primary sjs” when no other connective tissue disease is present. Sjogren’s Syndrome causes dry eyes, dry mouth, and it can also affect other major organ systems. Uncommonly, it can affect the central nervous system.

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See also Vitamin D Life

• Geoepidemiology of autoimmune rheumatic diseases file, not web page
• All items in category Autoimmune 164 items
• Hypothesis of Autoimmunity which includes Barr Virus and Vitamin D Deficiency – 2012
• Dry eyes associated with low vitamin D