Low Vitamin D strongly associated with Systemic Sclerosis - many studies

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Systemic Sclerosis decribed by GPT-4 - March 2023

Systemic sclerosis, also known as systemic scleroderma, is a rare autoimmune disorder characterized by the overproduction of collagen, which leads to the hardening and thickening of connective tissues in the body. This chronic condition affects multiple organs and systems, including the skin, blood vessels, muscles, and internal organs like the heart, lungs, kidneys, and gastrointestinal tract.

The exact cause of systemic sclerosis is not well understood, but it is believed to involve a combination of genetic and environmental factors that trigger an abnormal immune response. This immune response leads to inflammation and excessive collagen production, resulting in the fibrosis and thickening of tissues.

Systemic sclerosis is classified into two main subtypes:

• Limited cutaneous systemic sclerosis (lcSSc): This subtype primarily affects the skin on the hands, arms, face, and legs. It progresses more slowly and is generally associated with a better prognosis.
• Diffuse cutaneous systemic sclerosis (dcSSc): This subtype is more severe, as it affects not only the skin but also internal organs. It progresses more rapidly and can cause significant complications.

Symptoms of systemic sclerosis may include:
Skin thickening, hardening, and tightness
Raynaud's phenomenon (extremities turning blue or white in response to cold or stress)
Joint pain and stiffness
Muscle weakness
Fatigue
Gastrointestinal issues (e.g., acid reflux, difficulty swallowing)
Shortness of breath and pulmonary issues
Kidney problems
Heart complications

Diagnosis typically involves a combination of clinical evaluation, blood tests (to detect specific autoantibodies), and imaging studies to assess internal organ involvement. Treatment options may include medications to manage symptoms and slow disease progression, physical therapy, and, in some cases, immunosuppressive drugs. As systemic sclerosis can be a complex and potentially life-threatening condition, it is crucial for patients to receive ongoing care and monitoring from a multidisciplinary team of healthcare professionals.

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Systemic Sclerosis and vitamin D meta-analysis - Oct 2024

Vitamin D association with systemic sclerosis and its clinical features: A systematic review, meta-analysis, and meta-regression
Journal of Scleroderma and Related Disorders 61 references, PDF behind paywall
Tarak Dhaouadi dhaouaditarak at yahoo.fr, Awatef Riahi,...

Objectives:
The aim of this review was to summarize existing data on the contribution of Vitamin D level and/or deficiency/insufficiency to systemic sclerosis susceptibility and its clinical features.
Methods:
An electronic literature search for eligible studies among all papers published prior to 30 June 2024 was conducted through PubMed, EMBASE, Web of science, and Scopus databases. Meta-analyses estimating pooled raw mean differences, odds ratios, and Pearson r together with subgroup analyses and meta-regressions were performed for the association of Vitamin D with susceptibility to systemic sclerosis and disease presentation.
Results:
Combined analysis revealed a significant decrease in Vitamin D level in systemic sclerosis patients comparatively to healthy controls, with raw mean differences 95% CI = −11.68 [−15.43 to −7.92] ng/mL, p < 1 E-10. Likewise, Vitamin D insufficiency (Vitamin D < 30 ng/mL) and deficiency (<10 ng/mL) were significantly associated with systemic sclerosis; odds ratios 95% CI = 3.58 [2.59–4.95], p < 1 E-10 and odds ratios 95% CI = 7.67 [3.97–14.83], p < 1 E-10, respectively. Moreover, decreased Vitamin D level was significantly associated with interstitial lung disease occurrence (raw mean differences 95% CI = −3.61 [−6.93 to −0.3], p = 0.003), while Vitamin D deficiency was associated with increased systolic pulmonary arterial pressure, raw mean differences (95% CI = 4.17 [1.44–6.89], p = 0.003). Besides, Vitamin D level was negatively correlated with the modified Rodnan skin score, r (95% CI = −0.26 [−0.44 to −0.08], p = 0.004). Conversely, Vitamin D level was significantly increased in systemic sclerosis patients with cutaneous calcinosis, raw mean differences (95% CI = 4.18 [1.07–7.28], p = 0.008).

Conclusion:
This meta-analysis showed that decreased Vitamin D level was associated with

• susceptibility to systemic sclerosis,
• interstitial lung disease occurrence,
• increased systolic pulmonary arterial pressure, and
• higher modified Rodnan skin score.

Conversely, calcinosis was found to be associated with increased Vitamin D level.

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Vitamin D is the most common deficiency with Systemic Sclerosis - Dec 2022

Micronutrient Deficiencies in Systemic Sclerosis: A Scoping Review
Rheumatol . 2022 Dec 17;14:309-327. doi: 10.2147/OARRR.S354736. eCollection 2022.
Audrey D Nguyen 1, Zsuzsanna H McMahan 2, Elizabeth R Volkmann 1

Purpose: The primary aim is to identify the micronutrient deficiencies commonly reported in SSc. The exploratory aim is to evaluate associations between micronutrient deficiencies and SSc clinical manifestations.

Patient and methods: We conducted a scoping review of all published reports on SSc and nutrition in PubMed from its inception to August 2020. Clinical trials, observational studies, meta-analyses, and case series (with ≥20 cases) containing data on nutritional deficiency and SSc were included. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for reporting our findings. Two reviewers (ADN and ERV) studied the titles and abstracts of all search results with pre-specified inclusion and exclusion criteria.

Results: Among 790 retrieved publications, 35 full-length articles and 3 abstracts met the inclusion/exclusion criteria. Included studies took place across multiple geographic locations and included patients with both diffuse and limited cutaneous SSc.
Vitamin D deficiency was the most commonly reported deficiency described in SSc, followed by

• vitamin B12,
• vitamin B9,
• selenium,
• zinc, and
• iron.

In addition, some small studies found deficiencies in vitamins B1, B6, C, E, and A. While some studies reported associations between specific micronutrient deficiencies and SSc disease features (eg, interstitial lung disease was commonly associated with vitamin D deficiency and elevated homocysteine [Hcy]), the evidence to support these associations was not robust.

Conclusion: Micronutrient deficiencies are common in SSc and are associated with specific SSc features. Routine screening for micronutrient deficiencies may lead to early detection of malnutrition. Future studies are needed to understand how interventions to replete micronutrient deficiencies affect patient outcomes in SSc.
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Vitamin D in Systemic Sclerosis: A Review - Sept 2022

Nutrients 2022, 14(19), 3908; https://doi.org/10.3390/nu14193908
first author Mattia Perazzi

Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc);

Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies.

Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent;

Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis
 Download the PDF from VitaminDWiki 1

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Systemic Sclerosis review (SS associated with low Vitamin D) Nov 2021

Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review
Alexandra-Diana Diaconu ,1 Iustina Ostafie ,1 Alexandr Ceasovschih ,2,3 Victorița Șorodoc ,2,3 Cătălina Lionte ,2,3 Codrina Ancuța ,1,3 and Laurențiu Șorodoc 2,3

Background. Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. Aim. This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings.

Methods and Results. A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles.

Conclusions. Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients.
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Systemic sclerosis and Vitamin D literature review (97% had <20 ng)– Jan 2017

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature
Clinical Rheumatology, pp 1–8, Online: 09 January 2017, DOI: 10.1007/s10067-016-3535-z
Dilia GiuggioliEmail authorM. ColaciG. CassoneP. FallahiF. LumettiA. SpinellaF. CampomoriA. ManfrediC. U. ManziniA. AntonelliC. Ferri

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease’s features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A ) and 49 with (group B ) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B ); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (=30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = -0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level =30 ng/ml (8/15 vs. 6/34; p = 0.017).
In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.

Publisher wants $40 for the PDF, but the references online are free

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Systemic sclerosis and low vitamin D – June 2016

Low vitamin D status in systemic sclerosis and the impact on disease phenotype.
Eur J Rheumatol. 2016 Jun;3(2):50-55. Epub 2016 Feb 1.
Groseanu L1, Bojinca V1, Gudu T2, Saulescu I1, Predeteanu D1, Balanescu A1, Berghea F1, Opris D1, Borangiu A1, Constantinescu C1, Negru M1, Ionescu R1.
1Department of Internal Medicine, Division of Rheumatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Department of Internal Medicine, Division of Rheumatology, Sfanta Maria Clinical Hospital, Bucharest, Romania.
2Department of Internal Medicine, Division of Rheumatology, Sfanta Maria Clinical Hospital, Bucharest, Romania.
Most people with Systemic sclerosis have < 30 ng of vitamin D

OBJECTIVE:
Vitamin D has pleiotropic effects including immunomodulatory, cardioprotective, and antifibrotic properties and is thus able to modulate the three main links in scleroderma pathogenesis. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis and to analyze the associations between the concentration of vitamin D and the features of systemic sclerosis.
MATERIAL AND METHODS:
Fifty-one consecutive patients were evaluated for visceral involvement, immunological profile, activity, severity scores, and quality of life. The vitamin D status was evaluated by measuring the 25hydroxy-hydroxyvitamin D serum levels.
RESULTS:
The mean vitamin D level was 17.06±9.13 ng/dL. Only 9.8% of the patients had optimal vitamin D levels; 66.66% of them had insufficient 25(OH)D levels, while 23.52% had deficient levels.
No correlation was found between vitamin D concentration and age, sex, autoantibody profile, extent of skin involvement, or vitamin D supplementation. Vitamin D levels were correlated with the diffusing capacity of the lung for carbon monoxide (p=0.019, r=0.353), diastolic dysfunction (p=0.033, r=-0.318), digital contractures (p=0.036, r=-0.298), and muscle weakness (p=0.015, r=-0.377) and had a trend for negative correlation with pulmonary hypertension (p=0.053, r=-0.29).
CONCLUSION:
Low levels of vitamin D are very common in systemic sclerosis. Poor vitamin status seems to be related with a more aggressive disease with multivisceral and severe organ involvement, especially pulmonary and cardiac involvement.
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Systemic sclerosis Vit D: Low, varied with season, not change with 1,000 IU – June 2017

Vitamin D deficiency and clinical correlations in systemic sclerosis patients: A retrospective analysis for possible future developments.
PLoS One. 2017 Jun 9;12(6):e0179062. doi: 10.1371/journal.pone.0179062. eCollection 2017.
Trombetta AC1, Smith V2, Gotelli E1, Ghio M1, Paolino S1, Pizzorni C1, Vanhaecke A2, Ruaro B1, Sulli A1, Cutolo M1.

RESULTS:
Average 25(OH)D serum concentration was 18.7 ±9 ng/ml (<20 classified as deficiency). A significant correlation was found with presence/absence of lung bi-basal fibrotic changes (16.1 ±8 ng/ml and 20 ±10 ng/ml, respectively; p = 0.04). Peripheral vascular (p = 0.03), kidney (p = 0.02), gastrointestinal (p = 0.05) Medsger's DSS parameters were found to correlate with 25(OH)D serum concentrations. No significant correlations were observed with digital ulcers incidence, strictly correlated to patterns of microangiopathy, defined at NVC analysis (p<0.0001). Interestingly, no effects of treatment with oral colecalciferol (Dibase 1,000 IU daily for at least 6 months) were found on 25(OH)D serum concentrations in treated (18.8 ±10 ng/ml) or untreated (18.7 ±9 ng/ml) SSc patients (p = 0.81). A significant difference was observed among seasonal 25(OH)D serum concentrations (winter: 14.6 ±7.8 ng/ml, spring: 17.2 ±7.9 ng/ml, summer: 21.43 ±10 ng/ml, autumn: 20.2 ±10 ng/ml; p = 0.032) in all patients.

CONCLUSION:
Serum 25(OH)D deficiency was found to correlate with lung involvement, peripheral vascular, kidney and gastrointestinal Medsger's DSS parameters and with seasonality In SSc patients. Supplementation with oral colecalciferol was found not effective in increasing 25(OH)D serum concentrations. Therefore, for successful replacement, supra-physiological vitamin D3 doses or programmed UVB light exposure should be tested.
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Systemic Sclerosis + Raynaud’s => other health problems - 2016

Many Systemic Sclerosis Patients with Raynaud’s Syndrome Soon Develop Other Conditions Oct 2016

• "Of the initial 9,891 SSc patients followed during the EUSTAR study, 695 patients with a median age of 52.7 years had a baseline visit within one year after Raynaud’s onset, and developed skin sclerosis (75%); GI symptoms (71%); impaired diffusing capacity for monoxide below 80% (65%); DU (34%); cardiac involvement (32%); FVC below 80% (31%); increased PAPsys (14%); and renal crisis (3%)."

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See also VitaminDWiki

• Rare diseases hit fewer than 1 in 1500 people, but 1 in 12 people have a rare disease (vitamin might D help)
• Sclerodoma and vitamin D deficiency
• Autoimmune disease clusters run in families (polyautoimmunity) are associated with low vitamin D

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VitaminDWiki - Autoimmune

• 200 items in Autoimmune category
• Vitamin D and   MS    Asthma    RA    Diabetes    Gut   Allergy    Hay Fever    Lupus    Psoriasis
• Predicted 95% autoimmune cured by HIGH-DOSE vitamin D - 2014
• 10% of the UK have Autoimmune Diseases - Lancet May 2023 PDF is behind a paywall
  • Increase in 20 years : coeliac disease 2.19 X. Sjogren's syndrome 2.09, and Graves' disease 2.07
  • All 43 references are FREE on-line
• Autoimmune diseases fought by Vitamin D, especially if have more than 40 ng – Sept 2022
• The BEST Nutrient for Autoimmune Conditions (Vitamin D) - video May 2022
• The number 1 Deficiency behind All Autoimmune Diseases (Vitamin D) video - Dec 2023
• Autoimmune disease clusters run in families having low D
• How Vitamin D reduces inflammation, improves immunity and fights autoimmunity – review Dec 2018
• 120 doctors and 20,000 MS patients using high dose Vitamin D Dec 2018
• Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018
• Vitamin D Receptor is associated in over 58 autoimmune studies
• More autoimmune disease if higher pollution or lower UVB - Feb 2023
• Many autoimmune diseases associated with low vitamin D or poor Vit D genes – July 2019
  

See also web: consensus that ~50 diseases are autoimmune, ~50 more are suspected:

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19 VitaminDWiki studies in both Autoimmune and Vitamin D Receptor categories

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10,100 studies of "Systemic Sclerosis" "vitamin d" in Google Scholar as of March 2023

Google Scholar

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See also web

• http://www.scleroderma.org
  “The word “scleroderma” comes from two Greek words: “sclero” meaning hard, and “derma” meaning skin. Hardening of the skin is one of the most visible manifestations of the disease.”
  “It’s estimated that about 300,000 Americans have scleroderma. About one third of those people have the systemic form of scleroderma.”
  “Overall, female patients outnumber male patients about 4-to-1.”
  “It is known that scleroderma involves an overproduction of collagen”
  “Systemic scleroderma can involve the skin, esophagus, gastrointestinal tract (stomach and bowels), lungs, kidneys, heart and other internal organs. It can also affect blood vessels, muscles and joints.”

• Arthritis in patients with systemic sclerosis
  meta-analysis of 7 studies of SS and RA:, a prevalence of 26%
• Arthritis in systemic sclerosis: systematic review of the literature and suggestions for the performance of future clinical trials in systemic sclerosis arthritis June 2012
  "Musculoskeletal (MSK) pain is a frequent (between 40-80%) complaint of patients with systemic sclerosis (SSc). "

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