Introduction: Vitamin D deficiency (VDD) has been implicated as an important factor in the development or aggravation of systemic lupus erythematosus (SLE). Patients with SLE are especially prone to the development of VDD due to the nature of their illness and avoidance of sun exposure. However, the prevalence of VD status in Bahraini patients with SLE has not been studied before. Our aim is to study the prevalence of VDD in Bahraini cohort with SLE.

Material and methods: Fifty-eight Bahraini patients with SLE were included retrospectively in this study. The mean age of the patients, was 39.78years (16.0 - 61.0, STD 12.98). Most of the patients were females 50/58. The patients were followed at the rheumatology department at “Salmanyia medical complex” in Bahrain. Controls were fifty-eight age-matched healthy Bahraini subjects. Serum levels of 25 (OH) vitamin D3 were estimated using chemilumenescence immunoassay. Chi Square and T-Test were used for analysis a p value of≤0.05 was considered significant.

Results: There was statistically significant difference (p≤0.05) in the mean serum levels of vitamin D between patients (30.67nmol/l) and controls (39.95nmom/L). There was a statistically significant difference in Phos, PTH and ALP between patients and control group with a p≤0.001 for each. In the SLE patients there were 49.1% deficient, 45.1% insufficient and 3.8% were Optimal. In the controls; 27% was deficient, 52% insufficient and 21% optimal.

Conclusion: There was high prevalence of VDD in Bahraini patients with SLE. Both patients and controls had low vitamin D levels, however the patients had statistically significant lower vitamin D serum levels compared to the controls. Our study also highlights the need for studying the effects of correcting hypovitaminosis on the clinical disease activity in Bahraini SLE patients.

Keywords: vitamin D, SLE, bahrain

SLE, systemic lupus erythematous; VDD, vitamin D deficiency; Phos, phosphate; Ca, calcium; ALP, alkaline phosphatase; PTH, parathyroid hormone; Ds-DNA, double stranded-DNA; C3, complement 3; C4, complement 4; ANA, antinuclear antibody

Systemic lupus erythematous (SLE) is a multi-systemic autoimmune rheumatic disease, where environmental and genetic factors are reported to play a major role in the pathogenesis of the disease.¹ Low vitamin D status is considered one of these factors.² Usually, exposure to UVB light triggers the endogenous production of vitamin D in the skin and consequently will be converted to the metabolically active form in the kidney. In SLE patient’s photosensitivity is considered as a risk factor that could precipitate a flare up and aggravate disease activity.³ Therefore, use of sun protection is a keystone in maintaining remission in these patients. However, avoidance of sun exposure may diminish vitamin D synthesis and aggravated Vitamin D deficiency (VDD).⁴ A part from photosensitivity and the use of sun protection, there are other factors that may place SLE patients at increased risk of VDD such as; renal involvement^5-7 and use of medications for example; anticonvulsants, antimalarial, calcineurin inhibitors or glucocorticoids, that either alter the metabolism of vitamin D or down-regulate the functions of its receptors.⁸ A mechanism other than photo- protection that could intensify VDD in SLE patients is the production of autoantibodies directed against of vitamin D⁵.

Despite the evidence that many studies in different populations report a high prevalence of VDD among patients with SLE, it still remains under-recognized and under-treated in patients with SLE disease. A retrospective longitudinal study of Italian adult SLE patients showed that Vitamin D insufficiency detected in the wintertime can be either a predisposing factor for flare or the consequence of the flare itself in SLE patients.⁴ A Canadian clinical trial, has recommended vitamin D supplementation in patients with SLE as it showed increased vitamin D levels ameliorated inflammatory and hemostatic markers and showed a tendency toward subsequent clinical improvement.⁹ Despite plentiful exposure to sunlight throughout the year in Arabic or Gulf countries, VDD is highly prevalent in Saudi patients with SLE.¹⁰ But, also in Egyptian patients with SLE.³ A recent study from Taiwan has shown that serum vitamin D levels are inversely correlated with SLE disease activity at both active and inactive disease status, as well as, with an active LN disease stage.¹¹ On the other hand, association of VDD with the development of SLE or certain clinical features or laboratory parameters has been investigated and reported, but the mechanisms behind these associations are still needed to be clarified. Thus, in patients with SLE, VDD is associated with high levels of IL-6 and hematuria.⁶ Furthermore, it also associated with the quality of sleep.¹² On the contrary, vitamin D intake has been suspected as a risk factor for development of systemic lupus erythematosus in women, however, this has been disproved by.¹³

In the Kingdom of Bahrain, a population-based study has confirmed a high prevalence of VDD in healthy subjects, especially in females, and that showed a seasonal variation.¹⁴ Nevertheless, vitamin D status in Bahraini patients with SLE has not been investigated before. In this current study we would like to assess the prevalence of VDD in patients with SLE in Bahrain and to evaluate any association with the clinical predictors in such patients. Our aim is to conduct a retrospective cross-sectional study to investigate the vitamin D serum levels together with other biochemical parameters that generally considered to be involved in VD regulation such as; calcium, phosphorus, and parathyroid hormone (PTH), as well as, alkaline phosphatase as a marker for bone turnover. We aimed to investigate these parameters in a relatively large Bahraini cohort with SLE (58 patients), furthermore, to evaluate the impact of VDD on the exacerbation of pain and ill musculoskeletal health, as well as, clinical data, disease activity as assessed by presence of specific lupus autoantibodies (ds-DNA), but also ANA, C3 and C4 in these patients group. We also aimed to compare VD serum levels and the other biochemical parameters with the corresponding values in healthy controls.

Patients

Fifty-eight Bahraini patients with systemic lupus erythematous (SLE) were included retrospectively in this study. The demographic data are depicted in Table 1. The mean age of the patients was 39.78 years (range 16 -61years). However, most of the patients are female 50/58 (86.2%), while the male patients are only eight (13.8%). The patients were carefully followed at the rheumatology department at the main hospital in Bahrain “Salmanyia medical complex (SMC)”. All patients fulfilled the American College of Rheumatology (ACR) criteria from 1997 for the diagnosis of SLE.¹⁵ Fifty-eight healthy Bahraini subjects were used as controls. The controls are healthy Bahraini subjects and they are age-match, but only around 74% (35 females and 8 males) are also sex-matched.

Methods

The measurement of the serum level of 25(OH) Cholecalciferol, vitamin D (D3), was estimated using chemilumenescence immunoassay on Advia Centaur Analyzer (LoD 8.0 nmol/L). Serum levels < 30 nmol/L were considered as VDD, levels between 30 nmol/L and 50 nmol/L (≥ 30 ˂ 50) were classified as vitamin D insufficiency and optimal levels were ≥ 50 nmol/L. The complements, C3 & C4, were done by automated nephlometry using seimens reagents and BN Prospect machine. ANA test was done by indirect immunofloresence (IIF) method using hep2 slides from BIORAD Company. Anti-dsDNA levels were tested by automated ELIA using uniCAP machine from Phadi (pharmacia diagnostics -Thermo scientific co). Calcium, phosphorus and alkaline phosphatase levels in the serum were analyzed using spectrosphometric technique on Advia Chemistry XPT Analyzer. Intact PTH was determined in serum by two-site sandwich immunoassay, using direct chemiluminometric technology on Advia centaur analyzer (analytical sensitivity 0.265 pmol/L).

Statistical analysis

Data was entered and analyzed using SPSS version 23.0. Quantitative variables were presented as mean ± SD and qualitative variables were parented as count and percentages. Pearson correlation coefficient was used to measure the strength of linear relationship between Vitamin D and the risk factors, while Chi-Square was used to measure the association between Vitamin D deficiency and patient status. Independent 2-sample t-test was used to test the significance difference in population means. P-value < 0.05 was considered as statistically significant.

The demographic data of patients and controls is shown in Table 1. The mean age of patients is 39.77, range between 16– 61years (STD 12.98). The mean age for the controls is 44.81 (range 31 - 55, STD 5.46). Most of our patients are females 50/58 (86%) and the males are 8 (14%). In the control groups the females are 35/58 (60%) and only 23 are males (40%). There are statistical differences in patients compared to controls group in each of Phos, ALP, and PTH, but not the calcium. The results of the comparison of vitamin D and other parameters between SLE patients are depicted in Table 2. The mean serum level for vitamin D for SLE patient is 30.67 (range; 11 - 54 nmol/l), while for control the mean serum level of vitamin D is 39.59 (range 13 - 122 nmol/l). There is statistical significant difference in vitamin D serum levels between SLE patients and controls (p value = 0.005, (95% CI -15.13 – -2.70). (STD 12.11). On classifying the patients into deficient, insufficient and optimal (Figure 1), The current study demonstrated that the deficient SLE patients had lower serum levels compared to deficient control group and that deference was statistical significant (p = > 0.01) (Table 3).

Figure 1 Classification Of Vitamin D in Patients vs Controls.

Regarding, the patient group the deficient were 26 (49.1%), insufficient were 25 (47.1%), while only two patients had optimal levels (2.8%). Concerning the controls, deficient were 17 (29%), insufficient were 29 (50%) and optimal were 12 (21%). There is a statistically significant difference between patients and control groups in all risk factors (Phos, PTH and ALP) except Ca with a (p values ≤ 0.001 in each of the investigated parameters) (Table 2). Table 4, showed Sperman correlation in patients cohort. There were positive correlations between PTH and Phos, ALP and uric acid (r=0.277), (r=0.275) and (r=0.584), respectively. Also there is correlation between C3 and C4, (r=0.609), C3 and CRP (r=0.290), C3 and ALP (r=0.383) and C3 and Phos (r=0.451). Table 5, showed the Spearman correlation in the controls group. There are correlation between vitamin D and PTH (r=0.346), but also between PTH and Ph (r=0.282), and between Phos and calcium (r=0.282).

The current retrospective study is a cross-sectional study of a large cohort of Bahraini SLE patient and is the first study to investigate the vitamin D status in Bahraini SLE patients. We found that there is a high prevalence of VDD among Bahraini SLE patients. Almost half of our patients (49.1%) having vitamin deficiency with a level less than 30 nmol/L, while 96% of the patients have abnormal vitamin D levels (deficient or insufficient), this is in keeping with other studies in other parts of the world.¹⁶ In a Norway study the majority of recently settled immigrants from all age groups from the Middle East, South Asia and Africa showed that female adolescents from these regions had low levels of 25(OH) D.^17,18 It is important to note that even when patients were classified according to their vitamin D into three levels, we could still be able to show statistically significant difference in VDD class (vitamin D serum levels ˂ 30 nmol/l) between patients and controls. Our finding about high prevalence of vitamin D is consistent with another study in the region that has revealed VDD in Saudi patients with SLE.¹⁰

Surprisingly, our study failed to describe any correlation between hypovitaminosis and the risk factors for disease activity as assessed by the presence of specific lupus autoantibodies (ds-DNA) and/or low C3 and C4, or between hypovitaminosis and any of the investigated parameters including the risk factors for vitamin D disregulation in these patients group. These findings needed to be confirmed by another Bahraini study using any of the standard disease activity indices use for SLE disease. In contrast, in the control group the current study revealed a positive correlation between vitamin D and PTH at 0.01and between PTH and Phos at 0.05, however, a correlation between Ca and Phos at 0.01 was also found.¹⁹ The significance of low Vitamin D in our patients with SLE may be explained partly by the state of chronic inflammatory condition and renal involvements as many of our SLE patients have glomerular disorders (data not shown). It will be interesting to evaluate the effect of correcting hypovitaminosis D in these patients cohort and observing the frequency or severity of arthralgia and myalgia and also if there will be any association with any of disease activity indices. In conclusion, the current results about high prevalence of VDD suggest VDD as a possible risk factor for SLE in Bahrain and provide guidance for future studies looking at a potential role of vitamin D in the prevention and/or treatment of SLE. The present study also highlights the need for another study looking for the effects of correcting hypovitaminosis on the clinical status and disease activity in Bahraini patients with SLE disease.

None.

The author declares no conflict of interest.

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