SEARCH

SEARCH BY CITATION

Summary

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References

Background  Vitamin D could have important immunomodulatory effects in psoriasis.

Objectives  To measure 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and calcium serum levels in patients with psoriasis and the associations with some relevant clinical features.

Methods  A cross-sectional study was conducted over 1 year including 145 patients with chronic plaque psoriasis, 112 patients with rheumatoid arthritis (RA) and 141 healthy controls. 25(OH)D, PTH and calcium serum levels were measured in a centralized laboratory. Demography, comorbidities, disease severity and exposure time to sunlight (which was derived by questionnaire) were collected.

Results  The prevalence of vitamin D deficiency [25(OH)D levels < 20 ng mL−1] in patients with psoriasis was 57·8% vs. 37·5% in patients with RA and 29·7% in healthy controls (< 0·001). In winter, the prevalence of vitamin D deficiency rose to 80·9% in patients with psoriasis, to 41·3% in those with RA and to 30·3% in healthy controls (< 0·001). Patients with psoriasis or psoriatic arthritis did not differ in 25(OH)D serum levels nor in the prevalence of vitamin D deficiency. In the logistic regression analysis, vitamin D deficiency was associated with psoriasis independently of age, sex, body mass index, calcium, PTH levels and season of blood sampling. A limitation is that the study design does not allow a causal or temporal relationship between vitamin D deficiency and psoriasis to be established.

Conclusions  Vitamin D deficiency may be common in patients with psoriasis, especially in winter.

Much debate has taken place over the definition of vitamin D deficiency. Most agree that a serum level of 25-hydroxyvitamin D [25(OH)D] below 20 ng mL−1 (or 50 nmol L−1) is an indication of vitamin D deficiency, which has long been recognized as a pathological condition characterized by muscle weakness, rickets or osteomalacia. Vitamin D insufficiency, characterized as a serum level of 25(OH)D ranging from 10 to 30 ng mL−1 (25–75 nmol L−1) and without overt clinical symptoms, has recently become an important medical concern.1 Vitamin D insufficiency is extremely common in the U.S.A. and Europe where its prevalence is estimated to be as high as 50–80% in the general population.2–4 Defining a level of serum 25(OH)D as low or insufficient depends on the level that is defined as normal. Health authorities used different cut-offs for their definitions of sufficient and optimal status. The Institute of Medicine Committee found 20 ng mL−1 to be the level that is needed for good bone health for all individuals.5 Substantial evidence suggests that vitamin D plays a pivotal role in modulating dendritic cell function and regulating keratinocytes and T-cell proliferation.6,7 Epidemiological data have also confirmed that vitamin D deficiency may be a risk for development of autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis, systemic lupus erythematosus and Crohn disease.8–11

In this study we estimate the prevalence of vitamin D deficiency in patients with chronic plaque psoriasis and analyse the association of vitamin D with clinical features. The results show that vitamin D deficiency may be common in patients with psoriasis, especially in winter time.

Materials and methods

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References

Patients

This was a cross-sectional study including 145 adult patients with chronic plaque psoriasis (i.e. cases), 112 patients with RA and 141 healthy controls. Patients with psoriasis were recruited from those consecutively attending the outpatient clinic of the Dermatology Section of the University Hospital of Verona (Verona, Italy) and of the University Hospital of L’Aquila over a period of 1 year (from December 2009 to December 2010). Healthy controls were recruited from the partners or relatives of patients if not affected by psoriasis, in order to minimize the differences due to dietary intake of vitamin D. Patients with RA were recruited from those consecutively attending the outpatient clinic of the Rheumatology Section of the University Hospital of Verona. The rationale for including patients with RA is to have a control with another chronic immune-mediated inflammatory disease that has already been associated with vitamin D deficiency. Consequently, patients with RA represent a ‘positive’ control, other than a healthy population (‘negative’ control). The diagnosis of RA was confirmed by an experienced rheumatologist according to the 1987 American College of Rheumatology revised criteria.12 The inclusion criteria for the patients with psoriasis were a clinical diagnosis of chronic plaque psoriasis (i.e. lasting at least 6 months) independently of the actual Psoriasis Area and Severity Index (PASI) score; and the absence of systemic or topical antipsoriatic treatments, including phototherapy and/or topical vitamin D derivatives, for at least 3 months before study investigations. Cases and controls were recruited if aged > 18 years. Patients with other types of psoriasis (guttate, erythrodermic and pustular psoriasis), those with concomitant inflammatory bowel diseases (i.e. Crohn disease and ulcerative colitis) and those receiving therapeutic interventions that might influence vitamin D status, including bisphosphonates, systemic corticosteroids, vitamin D and calcium supplements, were excluded. All the subjects were white skinned.

Clinical evaluation

All subjects were interviewed and examined to collect age, sex, body mass index (BMI), alcohol consumption and smoking habit data. Alcohol consumers were defined as those who were used to consuming alcohol on a daily basis. Current smokers were defined as participants who smoked cigarettes daily or who had stopped smoking < 5 years before enrolment in the study. Nonsmokers were participants who had smoked < 5–10 packs of cigarettes during their lifetime or who had stopped smoking > 5 years before the enrolment. BMI was calculated as weight (kg) divided by height (m) squared. Psoriasis-related variables included disease duration and severity according to the PASI and the presence of psoriatic arthritis (PsA). The presence of PsA was diagnosed according to the CASPAR criteria.13 Patients with psoriasis were defined as having diabetes mellitus if they were taking hypoglycaemic medications or if a physician had ever told them that they had diabetes. Cases and controls were interviewed about the use of drugs affecting bone metabolism, including bisphosphonates, corticosteroids, calcium and vitamin D supplements. Exposure to sunlight from March to September (sun-exposure time) was quantified as < 10, 10–20, 20–30 or > 30 min daily.14 Patients and controls were asked to complete a diary card in each season.

Laboratory assessment

One serum sample was collected from each subject. Four aliquots were mailed on dry ice to the laboratory of the University of Verona and kept at −80 °C until measurement of parathyroid hormone (PTH), 25(OH)D and calcium using commercial enzyme-linked immunosorbent assay (ELISA) kits (IDS, St Joseph, MI, U.S.A.) with interassay coefficient of variation ranging from 5% to 15%. Patients were diagnosed as having vitamin D deficiency when serum level of 25(OH)D was measured as < 20 ng mL−1 or 50 nmol L−1. The serum 25(OH)D level is the best indicator of overall vitamin D status because this measurement reflects total vitamin D from dietary intake and sunlight exposure, as well as the conversion of vitamin D from adipose stores in the liver.1 C-reactive protein (CRP) was measured by a Behring nephelometer (Messer Grisheim GmbH, Bad Soden, Germany). Spring was defined as the time of the year ranging from 21 March to 20 June; summer from 21 June to 22 September; autumn from 23 September to 20 December and winter from 21 December to 20 March. Sixty-five out of 145 (47%) patients with psoriasis were sampled in spring, 30 (21%) in summer, 24 (16%) in autumn and 24 (16%) in winter. Healthy controls and patients with RA were sampled at approximately the same time as the patients with psoriasis, without significant differences between the proportions of patients sampled in the four seasons.

Statistical analysis

All analyses were performed using STATA 10.0 (StataCorp LP, College Station, TX, U.S.A.) and GraphPad 4.0 (GraphPad Software, San Diego, CA, U.S.A.). Data are expressed as mean (SD) or percentages. Skewed variables were logarithmically transformed to improve normality for statistical purposes and then back-transformed to their natural units for presentation in tables and figures. Statistical analyses included anova (for continuous variables) and χ2-test with the Yates correction for continuity (for categorical variables). The Pearson test was used to explore the linear correlation between PASI and 25(OH)D serum levels. Independence of the association of vitamin D deficiency and presence of psoriasis was assessed by multivariate regression analysis. In the fully adjusted regression model, age, sex, smoking habit, BMI, psoriasis, psoriasis duration and PASI score were also included as independent covariates. A P-value < 0·05 was considered statistically significant.

Results

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References

The characteristics of the study population are reported in Table 1. Patients with psoriasis were younger than patients with RA; they were more frequently smokers and alcohol consumers and had a greater BMI compared with those with RA and with healthy controls. Levels of 25(OH)D were significantly lower in patients with psoriasis compared with healthy controls (< 0·01), whereas there was no difference between patients with psoriasis and those with RA (< 0·45) (Fig. 1). Mean serum levels of 25(OH)D were 19·3 ± 10·8 ng mL−1 in female patients with psoriasis and 21·2 ± 11·5 ng mL−1 in male patients (< 0·3). There were no differences in PTH and calcium serum levels among the three groups (< 0·09 and < 0·2, respectively). There were no differences between the three groups in the prevalence of those exposed to sun > 30 min per day from March to September (< 0·4).

Table 1.   Characteristics of the study population
 Psoriasis (= 145Rheumatoid arthritis (= 112)Healthy controls (= 141)P-value
  1. BMI, body mass index; 25(OH)D; 25-hydroxyvitamin D; PTH, parathyroid hormone.

  2. aThe prevalence of those reporting exposure to sunlight > 30 min per day from March to September.

Male/female, n91/5422/9084/57 
Prevalence of men (%)6319600·001
Age (years), mean ± SD51·9 ± 13·357·9 ± 10·951·4 ± 7·00·01
Alcohol consumption (%)48·220·36·70·0001
Smoking habit (%)37·416250·002
BMI (kg m2), mean ± SD26·6 ± 4·124·9 ± 3·424·0 ± 3·70·001
Sun-exposure time > 30 min per day (%)a3329340·4
25(OH)D (ng mL−1), mean ± SD20·7 ± 11·324·0 ± 11·437·1 ± 27·60·001
PTH (pg mL−1), mean ± SD58·7 ± 24·555·8 ± 25·256 ± 18·90·09
Calcium (mg dL−1), mean ± SD9·5 ± 0·49·4 ± 0·29·3 ± 0·30·2
image

Figure 1.  Serum levels of 25-hydroxyvitamin D [25(OH)D] in healthy controls (white bar), patients with psoriasis (grey bar) and patients with rheumatoid arthritis (RA) (dashed bar). *< 0·001 vs. healthy controls.

Download figure to PowerPoint

The prevalence of 25(OH)D deficiency in the three groups is reported in Figure 2. The prevalence of patients with 25(OH)D deficiency was much higher in those with psoriasis compared with patients with RA (< 0·01) and healthy controls (< 0·001) (Fig. 2b). As expected, serum 25(OH)D levels varied significantly according to the season during which the blood sampling was taken. In particular, in those with psoriasis, serum 25(OH)D levels (ng mL−1) were 19·1 ± 7·6 (mean ± SD) in spring, 27 ± 14·5 in summer, 20·1 ± 12·6 in autumn and 16 ± 10·5 in winter (< 0·01). The proportion of psoriatic patients with vitamin D deficiency was higher during the winter, i.e. 81% (17 of 21 patients) compared with spring, i.e. 60% (39 of 65 patients), summer 37% (11 of 30 patients) and autumn 58% (14 of 24), < 0·01 (Fig. 2a). Similarly, the prevalence of vitamin D deficiency in winter increased to 41% in patients with RA and to 30% in healthy controls (< 0·001). Mean serum levels of 25(OH)D in patients with psoriasis (= 86) were similar to those in patients with psoriasis and concomitant PsA (= 59) (21·3 ± 11·6 vs. 19·7 ± 10·8 ng mL−1; < 0·4) as well as the prevalence of those with vitamin D deficiency (54% vs. 63%; < 0·2). The clinical and biochemical data of patients with psoriasis stratified by vitamin D deficiency (= 81) are reported in Table 2. As expected, serum 25(OH)D levels were significantly lower in patients with deficiency compared with those without deficiency (14·9 ± 3·1 vs. 46·5 ± 28·1; < 0·0001). In contrast, there were no differences in age, sex, smoking status, BMI, prevalence of diabetes or PsA, severity of psoriasis and serum levels of CRP, PTH and calcium between the two groups. In particular, there was no significant linear correlation between PASI score and 25(OH)D levels. In the multivariate regression analysis, vitamin D deficiency was associated with the presence of psoriasis [odds ratio (OR) 2·5; 95% confidence interval (CI) 1·18–4·89; < 0·01] independently of age, sex, BMI, calcium, PTH levels and season during which the blood sample was taken (Table 3). Moreover, 25(OH)D deficiency was directly associated with the PTH serum levels (OR 1·22; 95% CI 1·08–1·34; < 0·04).

image

Figure 2.  (a) Proportion of patients with psoriasis with vitamin D deficiency in different seasons. *< 0·01 vs. autumn, spring and summer. (b) Proportion of subjects with vitamin D deficiency *< 0·001 vs. healthy controls and patients with rheumatoid arthritis (RA). 25(OH)D, 25-hydroxyvitamin D.

Download figure to PowerPoint

Table 2.   Clinical and biochemical characteristics of patients with chronic plaque psoriasis
 With vitamin D deficiencya (= 81)Without vitamin D deficiency (= 64)P-value
  1. PASI, Psoriasis Area and Severity Index; CRP, C-reactive protein; 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone. a25(OH)D < 20 ng mL−1.

Sex (% men)62640·7
Age (years), mean ± SD52·0 ± 13·152·6 ± 15·30·8
Body mass index (kg m−2), mean ± SD26·4 ± 4·427·2 ± 4·20·3
Current smokers (%)32390·3
Type 2 diabetes (%)1040·2
Psoriasis duration (years), mean ± SD19·8 ± 13·121·7 ± 14·50·4
Psoriatic arthritis (%)35440·2
PASI, mean ± SD7·8 ± 126·4 ± 7·70·3
CRP (mg L−1), mean ± SD4·6 ± 6·03·6 ± 6·00·3
25(OH)D (ng mL−1), mean ± SD14·9 ± 3·146·5 ± 28·10·0001
PTH (pg mL−1), mean ± SD58·3 ± 24·459·3 ± 24·70·8
Calcium (mg dL−1), mean ± SD9·4 ± 0·49·5 ± 0·50·7
Table 3.   Independent predictors of 25-hydroxyvitamin D deficiency (= 81)
Independent variableOdds ratio95% CIP-value
  1. CI, confidence interval; PTH, parathyroid hormone.

Age (years)1·000·96–1·000·5
Sex (men vs. women)0·950·43–2·090·9
Body mass index (kg m−2)0·940·86–1·030·2
Calcium (mg dL−1)1·730·72–4·810·2
PTH (pg mL−1)1·221·08–1·340·04
Season1·390·95–2·040·08
Psoriasis (yes vs. no)2·51·18–4·890·01

Discussion

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References

The major finding of this study is that vitamin D deficiency is very frequent in patients with chronic plaque psoriasis and in those with PsA. This finding was more common (i.e. 80% of cases) in winter, but it was found also in summer in approximately 50% of patients. The association between vitamin D insufficiency and psoriasis was confirmed independently of age, sex, BMI, PASI score, PTH and the season in which the serum sample was taken. We found also a higher prevalence of vitamin D deficiency in patients with RA, as already reported.15

The finding of vitamin D deficiency in patients with psoriasis could be relevant for several reasons. Firstly, it has been clearly established that vitamin D deficiency is a risk factor for osteoporosis and increases the risk of falling in the elderly.16 An increased risk of male patients with psoriasis developing osteoporosis has been addressed in a large population-based case–control study conducted in Israel.17 Secondly, observational studies in large cohorts have shown significant associations between low levels of 25(OH)D and increased risk of diabetes mellitus, metabolic syndrome and cardiovascular mortality.18,19 Similarly, psoriasis is frequently associated with cardiometabolic comorbidities and with an increased cardiovascular mortality.20–22 Moreover, low levels of vitamin D may also have important implications in the pathogenesis of psoriasis. Vitamin D3 acts mainly on the vitamin D receptor to regulate keratinocyte growth and differentiation, but also has an influence on immune functions of dendritic cells and T lymphocytes.23,24 Vitamin D3 inhibits production of interleukin (IL)-2 and IL-6, blocks transcription of interferon-γ and granulocyte-macrophage colony-stimulating factor mRNA, and inhibits cytotoxic T cells and natural killer cell activity.25 Topical vitamin D derivatives, including calcipotriol (calcipotriene) and calcitriol, have immunomodulatory effects on monocytes, macrophages, T cells and dendritic cells.26 Indeed, topical vitamin D derivatives are extensively used as monotherapy or in combination with steroids for the topical treatment of psoriasis.27 Moreover, phototherapy increases the levels of serum 25(OH)D in patients with psoriasis and it has been proposed that narrowband ultraviolet (UV) B radiation may mediate its beneficial effect on psoriasis also by increasing endogenous vitamin D levels.28 That oral supplementation with vitamin D could be effective in the treatment of psoriasis was suggested some years ago.29,30 Furthermore, the recent finding of a resolution of adalimumab-induced psoriasis in a woman with RA after the use of high vitamin D doses for the treatment of vitamin D deficiency raises the interesting question on the possible use of vitamin D in the treatment of psoriasis.31 However, it is clear that more definitive evidence is required to demonstrate that a serum level of 25(OH)D < 20 ng mL−1 in psoriasis is pathologically low, and that clinical benefit would be gained from vitamin D supplementation.

Several conditions may contribute to low serum levels of vitamin D in the general population, including poor dietary intake of vitamin D; sun avoidance and/or negligible sun exposure, possibly related also to impaired quality of life; malabsorption due to inflammatory bowel disease, gluten enteropathy, gastric surgery, biliary disease, or intestinal bacteria overgrowth; use of antiseizure medications (e.g. phenobarbital or phenytoin) and long-term use of glucocorticoids.32 The reason for the higher prevalence of vitamin D deficiency in patients with psoriasis is not clear. However, we can exclude the possibility that this difference was related to different sun exposure between groups. Vitamin D deficiency has been already reported in other chronic immune-mediated inflammatory skin diseases including atopic dermatitis, vitiligo and chronic urticaria.31–33 A possible role of vitamin D deficiency in the development of these conditions has been also proposed.33–35

Once detected, vitamin D deficiency could be corrected, although no evidence of the possible benefits of vitamin D supplementation in reducing inflammation and/or the risk of other incident autoimmune diseases has yet been proven.36 Moreover, optimal dosage regimens for vitamin D remain uncertain. In general, for every 100 IU of vitamin D taken in, there is an increase of roughly 1 ng mL−1 (3 nmol L−1) in the serum level of 25(OH)D. Most trials assessing the effectiveness of the supplementation of 25(OH)D levels and the risk of fractures and falling have used daily doses of vitamin D between 400 and 1000 IU.37,38 Toxicity from vitamin D supplementation is very rare and consists principally of acute hypercalcaemia, which usually results from doses that exceed 10 000 IU per day.5 The tolerable upper level of daily vitamin D intake recently set by the Institute of Medicine is 4000 IU.5

This study has some limitations. Firstly, the cross-sectional study design does not allow a causal or temporal relationship between vitamin D insufficiency and psoriasis to be established. Prospective studies will be required to resolve these issues. Moreover, we did not assess daily vitamin D intake in foods; however, we excluded from the study patients receiving oral supplementation of vitamin D or drugs that interfere with calcium metabolism. Furthermore, we decided to choose the partners of patients with psoriasis as a control group in order to minimize differences due to different dietary intake of vitamin D. We chose patients with RA who were not matched for sex because the prevalence of RA is significantly higher in women, whereas psoriasis has a similar prevalence in men and women. If we had matched for sex we could have added a selection bias in the study.

In conclusion, vitamin D deficiency may be common in patients with psoriasis, especially in winter time. Therefore, patients could be routinely screened for vitamin D insufficiency for a more comprehensive management.

What’s already known about this topic?

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References
  •  Vitamin D deficiency, defined as serum levels of 25-hydroxyvitamin D [25(OH)D] < 20 ng mL−1, has recently become an important medical concern because of the confirmed association with osteoporosis, immune-mediated diseases, cardiometabolic diseases as well as with some cancers.

What does this study add?

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References
  •  Vitamin D deficiency may be common in patients with psoriasis, especially in winter time.

References

  1. Top of page
  2. Summary
  3. Materials and methods
  4. Results
  5. Discussion
  6. What’s already known about this topic?
  7. What does this study add?
  8. References