© Borgis - Postępy Nauk Medycznych 10/2012, s. 787-793
*Magdalena Kolanko1, Ligia Brzezińska-Wcisło2
Stężenie kalcydiolu u chorych na łuszczycę leczonych fototerapią UVB 311
Calcidiol level in patients with psoriasis treated with NB-UVB therapy
1Dermatology Department, Independent Public Clinical Hospital of Medical University of Silesia, Katowice
Head of Department: prof. Ligia Brzezińska-Wcisło, MD, PhD
2Dermatology Department, Medical University of Silesia, Katowice
Head of Department: prof. Ligia Brzezińska-Wcisło, MD, PhD
Wstęp. Naświetlania UVB 311nm (NB-UVB) mają wpływ na ekspresję genów substancji ważnych dla przebiegu łuszczycy poprzez zdolność do naskórkowej produkcji witaminy D.
Cel pracy. Celem pracy była ocena ich wpływu na stężenie 25(OH)D w surowicy w zależności od jego wyjściowej wartości oraz BMI, wieku, płci, nawyków żywieniowych i rekreacyjnych.
Materiał i metody. U 36 chorych mierzono stężenie 25(OH)D w surowicy metodą radioimmunologiczną-RIA przed rozpoczęciem fototerapii (T0), po 1., 3. i 6. tygodniu naświetlań (T1-T3) oraz po 1. i 5. tygodniu od jej zakończenia (T4-T5). Kontrolę (28 osób) badano w T0 i T4. Obliczano wartość PASI i BMI, oznaczano fototyp skóry oraz zbierano dane dotyczące stylu życia i danych demograficznych (ankieta).
Wyniki. Stężenie kalcydiolu w T0 było wyższe u pacjentów 33,21 ng/ml niż w kontroli 25,17 ng/ml (p < 0,05). Tendencja do niższych wartości kalcydiolu u osób starszych, kobiet oraz osób z mniejszym PASI nie była istotna (p > 0,05). Stwierdzono istotną różnicę przyrostu stężenia kalcydiolu pomiędzy oznaczeniem T0 a T4 – wyższą dla grupy o stężeniu < 25 ng/ml. W T4 nastąpił wzrost stężenia kalcydiolu u pacjentów – 50,16 ng/ml (p < 0,05), a spadek w kontroli – 21,37 ng/ml. W T5 stężenie kalcydiolu u pacjentów wyniosło 51,18 ng/ml. Codziennie spożycie różnych produktów nabiałowych podawało 11-45% badanych. Spożycie ryb deklarowano jako co najmniej raz w miesiącu.
Wnioski. Początkowe stężenie 25(OH)D wpływa na jego przyrost pod wpływem UVB 311 nm. Otrzymana w trakcie naświetlań dawka promieniowania zamaskowała sezonową zmienność stężenia kalcydiolu. Początkowe stężenie 25(OH)D nie zależy od wartości BMI i PASI, wieku oraz płci. Nawyki żywieniowe i habitualne mają wpływ na stężenie kalcydiolu.
Introduction. UVB 311nm phototherapy (NB-UVB) appears to influence the psoriasis significant factor’s genes expression by epidermal syntesis of vitamin D.
Aim. The aim of this research was to examine whether NB-UVB was able to induce 25(OH)D synthesis in relationship to its initial level and BMI, age, sex, nutrition and behavioral habits.
Material and methods. Serum 25(OH) D level was measured using RIA-method in 36 patients in T0 before the first dose of radiation, in T1-T3 during the treatment and in T4 and T5 accordingly in 1st and 5th week after the end of phototherapy. The parameters in controls (28 healthy adults) were measured in T0 and T4. Assessment included also: BMI, PASI, skin phototype, questionnaire (sun exposure, nutrition habits).
Results. Calcidiol level in T0 was higher in patients 33.21 nmg/ml vs. 25.17 ng/ml in controls (p < 0.05). The tendency to lower calcidiol levels among older, women and in patients with a lower PASI index value wasn’t significant (p > 0.05). There was a statistically significant difference in the increase of calcidiol level in patients between T0 and T4 – higher in the group of level < 25 ng/ml. There was an increase of calcidiol level in patients in T4 – 50.16 ng/ml (p < 0.05) and a decrease in controls – 21.37 ng/ml. In T5 calcidiol level in patients was 51.18 ng/ml. 11-45% participants reported consumption of different dairy products. The consumption of fish was declared as at least once a month.
Conclusions. The initial level of 25(OH)D has an impact on its growth by NB-UVB. The dose of UVB 311 nm received during the irradiation masked seasonal variability of the calcidiol level. There was no effect of BMI or PASI index values, age or gender on the calcidiol level. Nutrition and behavioral habits have an impact on the calcidiol level.
Psoriasis is a genetic inflammatory dermatosis characterized by abnormally exaggerated epidermal cellular turnover and erythematous lesions with silvery scale (plaque psoriasis). This disease constitutes a significant clinical problem due to its high frequency, chronic and recurrent course and no possibility of an ultimate cure (1, 2).
Due to its efficiency, safety and cost-effectiveness, one of the treatment modalities of moderate psoriasis is narrow-band UVB phototherapy (NB-UVB, with a maximum emission at 311 nm), which appears to influence the disease significant factor’s genes expression by epidermal syntesis of vitamin D (3, 4).
Calcitriol (active metabolit of vitamin D) has been shown to affect leucocytes by phosphorylation of their vitamin D receptor (VDR). Further studies showed that 1α, 25(OH)2D directly influences differentiation of Th2, increasing the production of interleukin IL-4, IL-5, IL-10 and TGF-β, and decreasing the synthesis of IL-2 and INF-γ. In this way calcitriol has an antiproliferative effect on keratynocytes (4). It was also confirmed that cacitriol produced in the skin may have an endo- and autocrine effect within keratinocytes themselves, but also a paracrine effect within the neighbouring cells, mainly by regulating their growth, differentiation and apoptosis, which also explains the efficiency of UVB therapy in psoriasis (5, 6).
Vitamin D is obtained in humans in two ways: by photoconversion of 7-dehydrocholesterol (7-DHC; this is its main source: 90-100%) or can be delivered with food (about 10%), especially fish (i.a. salmon, mackerel, sardines, tuna), milk, train-oil and artificial fortified butter and margarine (7, 8).
Calcidiol constitutes a basic form of vitamin D present in the blood with the biological half-time of 19 days (it can be stored in liver and fat tissue for longer time) (7, 9).
The aim of this research was to examine whether NB-UVB was able to induce serum 25(OH)D synthesis in relation to its initial level and PASI, BMI, age, sex, dietary and behavioral habits of patients with psoriasis treated with phototherapy.
Material and methods
The study was performed in 36 adult patients of the Dermatological Clinic of Medical University of Silesia (SUM) in Katowice (7 women and 29 men), aged 21-72 years (47.92+/-13.31 (mean+/-SD), BMI 19.03-36.42 kg/m2 (27.34+/-3.82), skin phototype II and III (Fitzpatrick) who were qualified to NB-UVB phototherapy due to moderate forms of psoriasis (PASI 8.4-17.4 (12.95+/-2.74)) and 28 healthy volunteers (13 women and 15 men), aged 26-59 years (43.78+/-8.15) and BMI 18.59-32.61 kg/m2 (25.61+/-4.02). Irradiation was conducted in the years 2008-2011, in periods during which the UVB doses present in the atmosphere at this latitude are irrelevant to the cutaneous production of vitamin D (November-March).
Three groups of patients were irradiated (12, 11 and 13 people) in a UV Dermalight-Medisun 2800 PC-AB cabin (Schulze&Böhm GmbH, Germany). The phototherapy started from 0.1 J/cm2 dose and consisted of 20 irradiations (total dose of 22.0 J/cm2) which lasted approximately 7 weeks. Patients assigned to each group started phototherapy on the same day. The control group of healthy volunteers for the patients from group I included 23 people, for group II – 17 people, and for group III – 20 people.
25(OH)D serum concentration was measured by radioimmunoassay method (DiaSource 25OH Vitamin D total-RIA-CT Kit) and was checked 6 times: before the first dose of irradiation (T0), after 1st, 3rd and 6th week of irradiation (T1-T3) and in week 1 and 5 after the end of phototherapy (T4-T5). The parameters of controls were measured 2 times (measurement concurrent with measurements T0 and T4 for patients).
The enrolled persons were subjected to a physical examination and biochemical serum tests assessing liver and kidney functions (creatinine, AlAT, AspAT, billirubine, prothrombin time, INR, fibrinogen in serum) in order to identify possible disturbances influencing vitamin D metabolism. Their dermatological status was assessed using the PASI index according to the Fredriksson’s guidelines, before, during and after the phototherapy. Complete remission was defined as PASI below 3 or its reduction by more than 90% (10, 11). The psoriatic patients were enrolled for UVB phototherapy if PASI was > 7.
The body mass index (BMI), Fitzpatrick’s skin phototype (12) and minimal erythema dose for UVB irradiation (MED, TH-1E lamp (Cosmedico Medizintechnik)) were defined before the treatment started. The data on the disease history in psoriatic patients and the dietary habits, exposition to sun irradiation, demographic information, concomitant diseases, drugs and diet supplements which can influence vitamin D levels in healthy and psoriatic patients were collected in the form of a questionnaire designed by us.
The persons enrolled into the study were informed about its aim and signed written consents for participation. The study obtained the agreement from the SUM Bioethical Commission in Katowice.
The obtained results were subjected to statistical analysis using StatisticaTM v 6.0 PL software. Significant differences were defined as p < 0.05.
The mean levels of 25(OH)D in serum (T0) of the patients were 33.21+/-16.14 ng/ml (mean+/-SD) and significantly higher in comparison to the control groups (p < 0.05) (fig. 1), and remained within the current recommendations (7). When analysing the group according to the month of the treatment’s beginning, higher levels of calcidiol were found at T0 in group 1 (phototherapy started in November (45.34+/-19.32 ng/ml) in comparison to group 2 and 3 (phototherapy started in January; 29.43+/-10.17 and 25.22+/-11.24 ng/ml, respectively – the level defined as hypovitaminosis). The results of mean 25(OH)D concentrations obtained for control group (25.17+/-11.59 ng/ml) and for each patient group (28.25+/11.24, 26.2+/-13,57 and 20.21+/-8.64 ng/ml, respectively) were defined as hypovitaminosis according to the current guidelines. Table 1 shows persons grouped according to the serum 25(OH)D concentration at T0.
Fig. 1. Serum 25(OH)D level (ng/ml) in patient and control groups at T0.
Table 1. Serum 25(OH)D level (ng/ml) in patient and control groups at T0.
|25(OH)D ||Recommended level|
|Hypo-vitaminosis (20-30 ng/ml)||Deficiency|
(< 10 ng/ml)
(> 80 ng/ml)
|Patient groups ||18 (50%)||10 (27.78%)||7 (19.44%)||0 (0%)||1 (2.78%)|
|Control groups ||16 (29.09%)||18 (32.73%)||19 (34.55%)||2 (3.64%)||0 (0%)|
After the end of phototherapy (T4), the mean serum levels of 25(OH)D in the combined tested groups increased to 50.16+/-22.29 ng/ml (p = 0.001) and were within the presently valid recommendations. The results obtained for each group were also compliant with the recommended levels and were 64.26+/-19.01, 31.9+/-15.3 and 49.63+/-19.92 ng/ml, respectively. When comparing with T0, a decrease in the percentage of patients with hypovitaminosis and vitamin D deficiency was observed, with an increase in the percentage of patients showing recommended vitamin D levels. The mean calcidiol levels in the control group of 21.37+/-14.5 ng/ml indicated hypovitaminosis and the similar results were obtained for group 1 and 3 (28.23+/15.59 and 25.22+/-13.48 ng/ml, respectively). The group 2 showed a decrease in 25(OH)D concentrations down to 10.45+/-5.9 (vitamin D deficiency). The increase in the percentage of patients with vitamin D deficiency together with a decrease in the percentage of patients with hypovitaminosis and the recommended 25(OH)D levels were observed. The mean calcidiol concentrations in patient groups at T4 were significantly higher in comparison to control groups (p < 0.05).
The significant changes in the level of serum 25(OH)D were observed in periods: T1-T2 (p < 0.001), T2-T3 (p < 0.001), T3-T4 (p < 0.05) and T0-T4 (p = 0.001). The lowest mean calcidiol levels were found at T0, while the highest at T2 (after 3 weeks from the beginning of phototherapy) and were 65.24+/-34.63 ng/ml, figure 2. Quantification performed at 5 weeks after the phototherapy ended (T5) showed that the mean 25(OH)D concentrations in the combined patient groups were at the level similar to that of T4 and were 51.18+/-21.63 ng/ml.
Fig. 2. The changes in the level of serum 25(OH)D (ng/ml) in all periods (T0-T5).
The psoriatic patients were divided into two groups – with the low (< 25 ng/ml, group I) and high (> 25 ng/ml, group II) initial calcidiol levels and compared between the groups for the increases in the parameter between the phototherapy start (T0) and its end (T4). It was concluded that the increase was the highest in the patients with initially low vitamin D levels in comparison to the patients with the higher values (p < 0.05) (fig. 3).
Fig. 3. Increase of 25(OH)D level (ng/ml) between T0 and T4 in the psoriatic patients divided into two groups – with the low (< 25 ng/ml, group I) and high (> 25 ng/ml, group II) initial calcidiol levels.
After the phototherapy ended, the PASI value was significantly lower than before the therapy (p < 0.0001) – it decreased from 12.95 (+/-2.74) to 1.63 (+/-1.75) (fig. 4). The percentage of patients with the improvement of their clinical status was 82.35% (PASI 75), and 47.05% (PASI 90).
Fig. 4. The changes in the PASI index value in all periods (T0-T5).
The lower levels of calcidiol were found (T0) in the sera of patients > 53 yrs (38.69 ng/ml), women (26.56 ng/ml) and in patients with the PASI value of < 12.5 (32.03 ng/ml) in comparison with patients < 53 yrs (28.31 ng/ml), men (34.82 ng/ml) and patients with the PASI value > 12.5 (34.88 ng/ml), although these differences were not statistically significant (p > 0.05). No significant relationships were observed (p > 0.05) between the phototherapy in history and the 25(OH)D concentrations (T0) in the tested patients groups, and between BMI, gender and 25(OH)D concentrations (T0) either in the combined patient groups or in the combined control groups.
No differences between particular patients groups in the serum calcidiol increases (ng/ml) (gender, age, PASI index, phototherapy in history) were found in the successive tests (T0-T4); p > 0.05.
The data on dietary habits were collected on the basis of our own questionnaire – it included questions on frequency of consuming products containing significant amounts of natural or artificially added vitamin D. A positive correlation was detected between the serum 25(OH)D concentrations and the frequency of margarine consumption (p < 0.005) in the patient groups. The mean level of 25(OH)D in the group of 13 persons (36%) consuming margarine every day was increased to over 40 ng/ml, and in the group of consuming less frequently than every day, consisting of 23 patients (64%), it was below 30 ng/ml. However, similar correlation was not found in healthy persons, for whom frequency of consuming margarine every day was similar (35% of the tested persons). Furthermore, no correlations were found between the serum 25(OH)D levels and the frequency of consuming milk and other dairy products, cod and fatty fish (mackerel, tuna, salmon, sardines) either in the patient or in the control groups.
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