Abstract: The recent success of vitamin D and its analogues in the treatment of psoriasis has generated extensive research into the role of vitamin D and calcium in this hyperproliferative skin disease. This study aimed at studying the calcium serum level in patients suffering from psoriasis. In this case control studies, 98 hospitalized cases with psoriasis were compared with 100 patients who were hospitalized due to other diseases. Two groups were matched for age and gender. The type of psoriasis, age and sex of patients and serum calcium and albumin levels in two groups were documented in a especial questionnaire. Of all 98 patients with psoriasis, 37.2% were hypocalcemic and 63.7% had normal serum calcium. There was no hypercalcemia. In other group 9% were hypocalcemic, 89 and 2% were normocalcemic and hypercalcemic respectively. In 64.9% of hypocalcemic psoriatic patients, low serum albumin was noted. But all of control group had normal levels. Hypocalcemia is a risk factor of psoriasis. It is better to include dairy as calcium resource in daily diet of patients suffering from psoriasis.
INTRODUCTION
Psoriasis is a chronic, recurrent skin disorder characterized histologically by cutaneous inflammation, increased epidermal proliferation, hyperkeratosis, angiogenesis, abnormal keratinization, shortened maturation time and parakeratosis (Gisondi et al., 2011; Hagforsen et al., 2012). Outbreaks often correlate with environmental triggers, often linked to nutritional deficiencies and poor eating habits (Hazarika, 2009). It is of important and prevalent skin diseases developing due to increasing epidermal cells multiplication. The disease may be intensified by different factors such that the lesions may extend, erythroderma (affecting of more than 90% of body skin) may develop and the patient may be hospitalized (Durakovic et al., 2001; Gold 2009). Evidently, it will result in intensifying kinds of disabilities as well as imposing heavy expenditures to the patients (Waqar and Sarkar, 2009). The best cure and remedy for psoriasis is to understand what is causing it in the first place. In addition to standard broadband ultraviolet radiation B (BUVB), (280-315 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) and heliotherapy (treatment with natural sunlight) have become important treatment modalities for psoriasis (Carlesimo et al., 2010; Osmancevic et al., 2010). Intracellular calcium plays an important part in the regulation of proliferation and differentiation of keratinocytes (Lebwohl et al., 2009). Some cases of various forms of this skin disease have been found to show disturbances in systemic calcium metabolism. Association of mild hypocalcemia with pustular psoriasis of von Zumbush, a rather severe form of psoriasis, has been observed (Plavina et al., 2008). Reportedly, hypoparathyroidism may cause the onset or aggravate psoriasis in patients with surgical hypoparathyroidism and primary hypoparathyroidism. Association of the disease with pseudohypoparathyroidism was also reported (Braun et al., 2007). Moreover, we showed that topical application of 1,2,5 dihydroxyvitamin D, [1,25-(OH),D], a well known calcitropic hormone, improved skin lesions of psoriatic patients (Lebwohl et al., 2007). It has been demonstrated that decrease of calcium serum leads to intensifying and extending the lesions in most patients. Accordingly, vitamin D systemic compounds and oral calcium are recommended to treat the problem (Noborio et al., 2006). The present study was conducted to evaluate calcium serum level in patients suffering from psoriasis.
MATERIALS AND METHODS
The present study was a case-control one. The case group was consisted of 98 psoriatic patients hospitalized at skin clinic of Sina hospital, Tabriz, Iran from Apr. 2010 to Apr. 2012. There were 100 non-psoriatic patients in the control group hospitalized in the same center. This study was approved by ethic committee of Tabriz University of medical sciences. Written consent was obtained from all the study population. Both groups were the same considering number of males and females and age range and calcium metabolism disorder was not seen in these groups. Calcium and serum albumin levels were measured in both groups. All tests were conducted in biochemical laboratory of Sina Hospital. Considering available kits, normal calcium range of serum was 8.2-10.5 mg dL-1 with ionized calcium. Other understudy variables included evaluating kind of psoriasis, serum calcium level considering kind of psoriasis and in the case group, calcium intake in daily diet as well as signs of muscular and skeletal pains in the subjects. SPSSTM, version 16 is the used statistical software program. The results were expressed as Means±SD The Chi-square test was used for statistical analysis. The level of statistical significance was set at a value of p<0.05.
RESULTS
Out of 98 hospitalized patients, 43 cases (43.8%) suffered from vulgaris psoriasis, 38 cases (38.7%) from dispersed pustular psoriasis, 4 cases (4.08%) from erythrodermic psoriasis and 14 cases (14.2%) from vulgaris psoriasis along with psoriatic arthritis. Considering serum calcium level, the patients were divided into three hypocalcaemia (low calcium serum level), normocalcaemia (normal calcium level) and hypercalcaemia (calcium level higher than normal). In this study, hypercalcaemia was not observed. Out of 98 hospitalized patients, low level of serum calcium was seen in 37 cases (37.2%) but hypocalcaemia frequency was only 9% in the control group (Table 1). Calcium serum levels were compared considering kinds of psoriasis. As observed, hypocalcaemia frequency is high in more severe kinds of psoriasis (e.g., erythrodermic psoriasis). Fifty seven point one percent of the patients with vulgaris psoriasis along with arthritis had hypocalcaemia since 42.9% of the patients had normal level of calcium (Table 2). Results obtained from evaluating other understudy variables are as follow: out of 37 patients with hypocalcaemia, 21 (56.8%) were male and 16 (42.3%) female. In hypocalcemic patients, 24 cases (64.9%) had low level of serum albumin, 22 cases (59.6%) suffered from dispersed muscular, skeletal pain as well as backache and 26 patients (72.7%) did not use calcium resources in their daily diet or their consumption was very insignificant. In all patients of the control group, serum albumin was at normal level.
| Table 1: | Demographic data of psoriasis patients |
| Table 2: | Frequency of calcium serum level (%) in hospitalized patients suffering from psoriasis |
DISCUSSION
Psoriasis is categorized as hyper proliferative diseases because increase of frequency of epidermis basal cells contributing in mitosis is seen in the disease. Considering available reasons of psoriasis, the main reason is not known but several factors such as family records and accompanying with some Human Leukocytes Antigens (HLA) has been mentioned (Duweb et al., 2005). Several studies have approved the close relation between psoriasis and serum calcium level. The researches demonstrated that hypocalcaemia resulting from psoriasis intensifies following parathyroidectomy such that psoriasis intensification and atopic dermatitis have been introduced as manifestations of hypoparathyroidism (Cuevas and Arrazola, 2005). On the other hand, hypocalcaemia may lead to developing of kinds of generalized pustular psoriasis (Lee et al., 2005). It should be remembered that intracellular calcium is kept in mitochondria, reticulum sarcoplasmic and reticulum endoplasmic. Activating cell cytoplasmic membrane receptors lead to rerelease of calcium in cytosol. If concentration of the free intracellular calcium decreases, it will either actively release from free intracellular resources or enter the cell actively and through adenosine triphosphatase (Guilhou, 1998). About 45% of serum calcium connects to albumin, therefore, serum calcium especially ionized calcium level depends on serum albumin level and it is better to measure serum albumin level while measuring serum calcium level. Under hypoalbuminosis conditions, the measured number should be corrected in order to obtain real numbers (Matsushita et al., 2005). According to the researches, there are several evidences regarding involvement of nucleotid in pathogenesis of psoriasis such that decrease of circular adenosine monophosphate result in increase of cellular proliferation in psoriatic patients (Dimon-Gadal et al., 1998). It seems that increase of phosphorylase kinase activity involving in adenosine triphosphatase metabolism result in psoriasis intensification and decrease of its activity due to treating with calcipotriol result in psoriasis recovery. It can be attributed to calcium metabolism changes (Dessy et al., 2011). Several studies have indicated to calcium role in controlling cellular multiplication and differentiation. On the other hand, measuring epidermis calcium concentration in patients suffering from psoriasis demonstrated low level of the material and justify parakeratosis in such conditions (Shahriari et al., 2010). Prescribing some calcium channels blockers such as diltiazem in some patients have resulted in developing psoriasiform rashes. The lesions were recovered after stopping the drugs consumption (Brown and Slatopolsky, 2008). According to the results of the present study, low level of serum calcium was observed in all erythrodermic and half of the patients suffering from dispersed pustular psoriasis. The results are in correspondence with other researches (Kitamura et al., 1993). Additionally, hypocalcaemia in the control group is clearly less frequent than the case group (9% vs. 37.2%). Since erythroderma and dispersed pustular psoriasis are regarded as more severe kinds of psoriasis, more frequency of hypocalcaemia is justifiable in the patients and it can be considered as one of the factors leading to lesions intensification or extension. However, calcium replacement has been conducted in all patients. Also, as mentioned previously, it is better to calculate corrected amounts of serum ionized calcium in patients suffering from hypoalbuminemia. In spite of correcting the numbers, calcium was at normal range just in few patients and it is practically ignorable. According to the same evidences, use of vitamin D compounds such as calcipotriol has been recommended in treating psoriasis. Vitamin D analogues play a significant role in cellular multiplication and differentiation in addition to calcium balance (Gumowski-Sunek et al., 1995). Meanwhile, vitamin D facilitates entrance of calcium inside the cells (through calcium-dependent proteins) and imposes its hormone effects in cell differentiation. Immune modulation feature can be regarded as another effect mechanism of these compounds (Reichrath, 2007). Therefore, vitamin D analogues result in recovery of psoriatic lesions through different mechanisms.
CONCLUSION
It is better to include dairy as calcium resource in daily diet of patients suffering from psoriasis. Additionally, considering that vitamin D compounds such as calcipotriol are topical drugs and lack severe systemic complications, their role in treating psoriatic lesions should be taken into account. In case of intensification of psoriasis lesions, it is important to pay attention to hypocalcaemia as an important factor.