Vitamin D production in psoriasis patients increases less with narrowband than with broadband ultraviolet B phototherapy

Background: Phototherapy of psoriasis is an effective treatment. In addition to standard broadband ultraviolet radiation B (UVB), (280–320 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) has become an important treatment for psoriasis. The same wavelength range of UVB (290–315 nm) induces synthesis of vitamin D. The aim was to compare the effect of broadband with NBUVB therapy on vitamin D synthesis in patients with psoriasis.
Methods: Sixty-eight Caucasian patients (17 women and 51 men) mean age 54.1 ± 16.0 years, with active plaque psoriasis, were treated with broadband UVB ( n =26) or NBUVB ( n =42) two to three times/week for 8–12 weeks. The serum concentrations of 25-hydroxyvitamin D (25(OH)D3), 1,25-dihydroxyvitamin D (1,25(OH)₂D3), intact parathyroid hormone (PTH), calcium and creatinine were measured before the first exposure and after the last dose of radiation.
Results: In broadband UVB treated patients, 25(OH)D3 increased from 37.9 ± 16.9 to 69.4 ± 19.7 ng/ml ( P <0.0001) and in patients treated with NBUVB from 34.8 ± 11.9 to 55.3 ± 17.6 ng/ml ( P <0.0001) and P =0.008 between the treatment groups. PTH decreased on broadband UVB ( P <0.05). The serum concentrations of 1,25(OH)₂D3, calcium or creatinine remained unaltered.
Conclusion: Serum 25(OH)D3 in psoriasis patients increased less with NBUVB than with broadband UVB phototherapy. Psoriasis improved on both regimens.     

Vitamin D3 levels and bone mineral density in patients with psoriasis and/or psoriatic arthritis

Limited data are available on the vitamin D₃ status and bone mineral density (BMD) of patients with psoriasis or with psoriatic arthritis. Our study intended to explore possible correlations between vitamin D status and BMD, as well as among these parameters and the features of the underlying disorder. Seventy‐two patients with psoriasis/or psoriatic arthritis (female : male ratio, 40:32; mean age, 58.5 ± 11.6 years; mean duration of follow up, 142.7 ± 147.7 months) participated in the study. We evaluated the characteristic clinical features of the underlying disease, performed bone densitometry of the lumbar spine and the hip region, measured the serum vitamin 25(OH)D₃ levels of the patients, and undertook the statistical analysis of the relationships between the clinical and the laboratory parameters. The proportion of patients with a low BMD value did not exceed that seen in the general population. We found an inverse correlation between the serum level of vitamin 25(OH)D₃ and body mass index, as well as between the former and the severity of skin involvement. Furthermore, the activity of psoriatic arthritis was significantly higher in patients with inadequate vitamin D₃ status. In patients with psoriatic arthritis, BMD significantly exceeded the values measured in patients suffering from psoriatic skin lesions only. Our findings suggest the importance of evaluating the vitamin D₃ status and screening for comorbid conditions in patients with psoriasis or psoriatic arthritis. This appears justified, in particular, due to the possible role of hypovitaminosis D₃ in provoking the development of skin lesions and joint symptoms.     

Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis

Background Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D₃ synthesis. Objective The aim of the study was to investigate the effect of climate therapy on vitamin D₃ synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. Methods Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24–65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8–18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients’ individual skin UV doses based on UV measurements were estimated. Results Sun exposure for 15 days lead to a 72.8% (± 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25‐hydroxyvitamin D [25(OH)D] increased from 57.2 ± 14.9 nmol/L before therapy to 104.5 ± 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25‐dihydroxyvitamin D [1,25(OH)₂D] increased from 146.5 ± 42.0 to 182.7 ± 59.1 pmol/L (P = 0.01); the ratio of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A₁c (HbA₁c) levels decreased from 5.6 ± 1.7% to 5.1 ± 0.3% (P < 0.0001). Conclusion Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.     

Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with thiazide diuretics in a case of psoriasis

Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of inflammatory skin diseases such as psoriasis. Hypercalcemia has not been previously reported during treatment with topical tacalcitol. We experienced a male patient with psoriasis and hypertension whose conditions were treated with tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and urinary excretion of calcium increased gradually. On day 28 of the treatment, his serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was terminated, seven days later, the serum calcium level had returned to the reference range without any specific treatment. The present case is the first report of hypercalcemia induced by vitamin D3 ointment and thiazide simultaneously.     

Combination therapy with vitamin D analogues

Monotherapy with vitamin D analogues has been shown to be effective in the treatment of psoriasis. Vitamin D analogues have also been used in combination with other topical therapies, systemic therapies and phototherapy. In many instances, the efficacy of these other treatments can be maximized and adverse effects minimized when combined with vitamin D analogues. The combination of a topical corticosteroid with a vitamin D analogue can work synergistically to improve efficacy and reduce the side-effects from both treatments. However, caution must be used when mixing the two agents, as some topical corticosteroids will result in the degradation of the vitamin D analogue. Benefit from phototherapy is also increased when using vitamin D analogues, so that greater improvement occurs with fewer treatments. Effects on minimal erythema dose must be considered and the potential for ultraviolet blocking by vitamin D analogues may affect treatment. Some vitamin D analogues may also be susceptible to degradation by certain wavelengths of ultraviolet light. Combining vitamin D analogues with systemic agents exerts a dose-sparing effect, thus reducing the possibility of side-effects, but such combinations require further study. As long as treatments are used correctly, the benefits of combination therapy with vitamin D analogues usually outweigh the few drawbacks.     

UV-based therapy and vitamin D

The ultraviolet (UV) light spectrum has long been known to induce biologic effect on the skin. For a large number of cutaneous disorders, phototherapy and photochemotherapy are effective therapeutic options with excellent safety profiles and well-documented side effects. Despite their ease of administration and benefits, phototherapeutic treatment modalities require appropriate space for the equipment, trained staff, and patient education prior to initiating treatment. However, when the initial barriers to treatment can be overcome, UV therapy can offer patients significant relief from their cutaneous disease. Furthermore, UVB-based phototherapy can produce significant alteration to vitamin D levels. With the recent research implicating association of low vitamin D levels with a variety of health conditions, whether patients receiving phototherapy or, more specifically, those getting vitamin D supplement may be protected from these diseases remains to be established.     

Increased 25(OH)D3 level in redheaded people: Could redheadedness be an adaptation to temperate climate?

About 1-2% of European population are redheaded, meaning they synthesize more pheomelanin than eumelanin, the main melanin pigment in humans. Several mutations could be responsible for this phenotype. It has been suggested that corresponding mutations spread in Europe due to a founder effect shaped either by a relaxation of selection for dark, UV-protective phenotypes or by sexual selection in favour of rare phenotypes. In our study, we investigated the levels of vitamin D precursor 25(OH)D3 (calcidiol) and folic acid in the blood serum of 73 redheaded and 130 non-redheaded individuals. In redheaded individuals, we found higher 25(OH)D3 concentrations and approximately the same folic acid concentrations as in non-redheaded subjects. 25(OH)D3 concentrations correlated with the intensity of hair redness measured by two spectrophotometric methods and estimated by participants themselves and by independent observers. In non-redheaded individuals, 25(OH)D3 levels covaried with the amount of sun exposure and intensity of suntan while in redheaded individuals, this was not the case. It suggests that increased 25(OH)D3 levels in redheaded individuals are due to differences in physiology rather than in behaviour. We also found that folic acid levels increased with age and the intensity of baldness and decreased with the frequency of visiting tanning salons. Our results suggest that the redheaded phenotype could be an evolutionary adaptation for sufficient photosynthesis of provitamin D in conditions of low intensity of UVB radiation in central and northern parts of Europe.     

The vitamin D receptor gene polymorphism rs1544410 T/T genotype as a predictor of factor vitamin D thresholds deficiency in patients with psoriasis vulgaris—A preliminary study

Background

Many clinical features of psoriasis include a rash with itchy, scaly patches, most frequently on the knees, elbows, trunk, and scalp. By studying genes involved with psoriasis receptivity, the pathologic pathways of psoriasis become clearer and more understood.

Aim

To predict the participation of rs1544410 in serum vitamin D levels (SDL) in psoriasis, psoriasis susceptibility, and severity.

Patients/Methods

One hundred five patients with psoriasis were categorized by body surface area as mild, moderate, and severe. SDL and genetic analysis of rs1544410 were performed using polymerase chain reaction and standard Sanger methods.

Result

Our findings revealed that SDL were higher in healthy subjects than in patients. The rs1544410 genotype TT was more prevalent in patients, while CT was more prevalent in controls. Our findings revealed that the T alleles were frequently more in the patient group than in the controls. (p ≤ 0.001). While in healthy normal individuals, the C alleles were frequently more (p ≤ 0.001). SDL are lower in patients with the TT genotype. Patients with moderate form of psoriasis have higher SDL than those with mild or severe form.

Conclusion

rs1544410 polymorphism has been linked to a higher probability of psoriasis and SDL deficiency. However, grander scale studies in a larger number of people are necessary.     

Combination of photochemotherapy (PUVA) and ultraviolet B (UVB) in the treatment of psoriasis vulgaris

Nineteen patients with psoriasis vulgaris were treated with a combination of psoralen-ultraviolet A (PUVA) and ultraviolet B (UVB) on the right side of their bodies and with PUVA therapy alone on the left side. Herein is an analysis of the results. There were no significant differences in the mean number of treatments, the mean UVA dose at clearing, or the mean cumulative UVA dose between the PUVA-UVB side and the PUVA side. However, in 4 cases, the PUVA-UVB side cleared more rapidly than the PUVA side. Interestingly, patients who received PUVA-UVB on one side and PUVA on the other required fewer treatments, a lower ultraviolet (UV) dose at clearing, and a lower cumulative UV dose than did patients who were treated with only PUVA monotherapy or UVB monotherapy, following the same protocol. This combined method may be useful in the treatment of chronic psoriatic patients, because of rapid clearing and a marked reduction in the total cumulative UV radiation. However, further follow-up studies are indicated due to the long-term side effects of combined UV radiation.     

Comparison of the efficacy of calcipotriol and maxacalcitol in combination with narrow-band ultraviolet B therapy for the treatment of psoriasis vulgaris

BACKGROUND: Combination treatment with topical vitamin D(3) and narrow-band ultraviolet B (UVB) radiation is effective against psoriasis vulgaris. We compared the efficacy of the topical vitamin D(3) derivatives calcipotriol and maxacalcitol in combination therapy. MATERIALS AND METHODS: In this retrospective observational study, 21 patients admitted to Nagoya City University Hospital between April 2001 and September 2004 were enrolled. RESULTS: Combination treatment with calcipotriol or maxacalcitol and narrow-band UVB was effective against psoriasis vulgaris. Calcipotriol induced a more rapid improvement and required lower levels of narrow-band UVB irradiation to be effective. Serum calcium levels were slightly increased after 4 weeks of treatment, but there was no significant difference between the two groups. No other adverse effects were observed in either of the two groups. CONCLUSION: The findings of this retrospective observational study indicated that combination treatment with topical vitamin D(3) derivatives and narrow-band UVB is effective against psoriasis without any obvious side-effects. These findings provide further evidence that calcipotriol has advantages over maxacalcitol regarding the narrow-band UVB-accumulated treatment dose and improvement rate of psoriasis area and severity index (PASI) scores.     

Biological therapy in genital psoriasis in women

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA‐G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA‐G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti‐IL17 (Secukinumab, Ixekizumab) and anti‐IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti‐TNFα patients, 6 anti‐IL17 and 1 anti‐IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA‐G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.     

Narrowband UVB phototherapy for psoriasis: Results with fixed increments by skin type (as opposed to percentage increments)

Many authors currently advocate 10-20% dosage increments between phototherapy sessions when treating psoriasis with narrowband ultraviolet B (UVB). However, such regimens are associated with a risk of significant erythema. In order to reduce this risk, a fixed increment regimen was developed using increments ranging from 30 mJ/cm2 for skin type II to 150 mJ/cm2 for type VI. Starting doses, also based on skin type, range from 180 to 400 mJ/cm2. Data from 20 patients with moderate to severe plaque psoriasis [13 male, 7 female, age range 17-74, skin types II (3), III (10), IV (3), V (1), VI (3)] completing 27 courses of phototherapy of more than 3 weeks' duration between 8/96 and 12/97 were compared. Complete, or near-complete clearing occurred in 8/13 courses (62%) with a frequency of attendance (during the initial 24 sessions) of >2.5 sessions per week, 4/8 (50%) with a frequency of 2.0-2.5, and 1/6 (17%) with a frequency of <2.0. In the subset of patients taking low-dose oral retinoids, rates of clearing were higher. Overall, 10 of 20 patients (50%) cleared, usually within 24-30 sessions. The average maximum dosage in such cases was 1400 mJ/cm2. There were only 13 instances of minor erythema, and 1 instance of severe erythema resulting in desquamation and requiring interruption of treatment. This was due to the inadvertent administration of an excessive 300 mJ/cm2 increment to a type VI patient. In summary, using a conservative fixed increment regimen, clearing of psoriasis is possible while minimizing the risk of serious erythema. Results are enhanced when patients attend 3 phototherapy sessions per week.     

NB-UVB治疗银屑病的疗效及其对皮损角质形成细胞周期蛋白D1和E的影响

目的：观察311nm窄谱中波紫外线（NB—UVB）对银屑病的疗效，以及治疗前后皮损角质形成细胞周期蛋白D1、E（cyclinD1、E）的表达。方法：以Cosmedico皮肤检测仪检测25例患者的最小红斑量（IVIED），以PASI评价疗效，并以免疫组化法检测皮损部位cyclinD1、E的表达。结果：NB—UVB治疗银屑病的临床有效率为92％；光疗前绝大多数皮损可检测到两种蛋白，但分布于不同的表皮细胞层，光疗后皮损中cyclinD1、E的表达较治疗前明显下降（均P〈0．01）；cyclinD1、E表达情况与PASI值呈正相关。结论：NB—UVB治疗银屑病安全、有效；下调表皮角质形成细胞中cyclinD1、E的表达可能是NB—UVB治疗银屑病的机制之一。     

Evidence of a marked 25-hydroxyvitamin D deficiency in patients with congenital ichthyosis

BACKGROUND: Vitamin D is essential for bone mineralization, and its deficiency may be the cause of skeletal fractures and osteomalacia. Geographical or ethnic factors may modulate the cutaneous synthesis of vitamin D. We hypothesized that major changes in keratinization may similarly alter the cutaneous synthesis of vitamin D. OBJECTIVES: To explore calciotrophic hormones, parameters of bone remodelling and bone mineral density (BMD) in nine patients with non-bullous congenital ichthyosis. PATIENTS AND METHODS: Six patients were European, three were North African. Four had received acitretin over a long period of time. A complete biological investigation, including serum and urinary calcium and phosphorus, calciotrophic hormones [intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D)], bone formation and resorption markers, was performed on all patients during the winter season and repeated among four patients after summer. BMD was measured in all patients. RESULTS: All patients had a marked 25-(OH)D deficiency, clearly below the deficiency threshold of 25 nmol/L. Patients from North Africa had a greater deficiency than European patients, perhaps because of the difference in skin pigmentation. iPTH remained normal in European patients but was elevated among the North Africans. After sun exposure, an improvement in vitamin status was visible in only one patient. Bone formation and resorption markers remained normal. Femoral neck osteodensitometry indicated values near the osteopaenic threshold in two young North African females. No deleterious effect of retinoids on vitamin D metabolism was observed. CONCLUSION: Patients, and in particular pigmented patients, with congenital ichthyosis present a severe deficiency in vitamin D. Care provided to protect the skeletal future of these patients involves measuring BMD and prescribing supplementation.     

Anti-inflammatory effects of tacalcitol (1,24(R)(OH)2D3, TV-02) in the skin of TPA-treated hairless mice

Tacalcitol (1,24(R)(OH)2D3, TV-02) inhibited the TPA-induced inflammatory cell infiltration (largely neutrophils) histopathologically and myeloperoxidase (MPO) activity dose-dependently. Tacalcitol inhibited the mRNA expression and protein production of TPA-induced macrophage inflammatory protein-2 (MIP-2) and KC, the functional analogue of human interleukin (IL)-8, in the skin. Immunohistochemical staining of the TPA-applied skin revealed that mast cells expressed MIP-2, whereas KC was observed in keratinocytes, fibroblasts and outer root sheath of hair follicles. Furthermore, tacalcitol inhibited TPA-induced mast cell degranulation 24 hr after application without influence on the total number of mast cells. In this study, tacalcitol was found to have an inhibitory effect on cutaneous inflammation such as inhibition of neutrophil infiltration, MIP-2 and KC production, and mast cell degranulation in TPA-treated hairless mice. These results suggest that tacalcitol modulates cutaneous inflammation as well as keratinocyte proliferation and differentiation, and the inhibitory effect of tacalcitol on cutaneous inflammation may contribute to clinical the effectiveness in the treatment of psoriasis.