Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation

Background Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear. Objectives We sought to investigate the relationship between disease activity and systemic inflammation in patients with psoriasis, and macrovascular and microvascular function. Methods Fifty‐two patients with psoriasis (mean ± SD age 44 ± 8 years; 38 men) were compared with 50 age‐ and sex‐matched controls. Baseline demographics and high‐sensitivity C‐reactive protein (hs‐CRP) level were recorded for each subject. Psoriatic disease activity was assessed using the Psoriasis Area and Severity Index (PASI). Arterial stiffness and endothelial function were assessed using brachial to ankle pulse wave velocity (baPWV) and digital hyperaemic response measured using the peripheral arterial tonometry (PAT) index. Results Patients with psoriasis had significantly higher hs‐CRP (mean ± SD 5·3 ± 5·1 vs. 1·9 ± 1·6 mg L^?1, P < 0·01) and baPWV (mean ± SD 14·5 ± 2·5 vs. 13·2 ± 1·6 m s^?1, P < 0·01) but not PAT index (mean ± SD 2·06 ± 0·59 vs. 2·10 ± 0·44, P = 0·70) than controls. There was significant correlation of hs‐CRP with baPWV (r = 0·51, P < 0·01) and with PASI (r = 0·48, P < 0·01). Multiple linear regression analysis demonstrated that baPWV is independently correlated with age, fasting glucose and hs‐CRP (P < 0·05), but does not predict PAT index. Each mg L^?1 increase in hs‐CRP accounted for an increase in baPWV of +0·12 m s^?1 (95% confidence interval 0·01–0·22, P = 0·03). Conclusions Young patients with psoriasis have increased arterial stiffness but not microvascular dysfunction compared with healthy controls. More importantly, hs‐CRP positively correlated with, and independently predicted, arterial stiffness. This suggests that systemic inflammation in patients with psoriasis is associated with premature atherosclerosis.     

Elevation of serum epidermal growth factor and interleukin 1 receptor antagonist in active psoriasis vulgaris

Background Psoriatic plaques present a complex expression profile, including high levels of cytokines, chemokines and growth factors. Circulating cytokines have been suggested to reflect the activation status of the inflammatory process. Objectives To analyse 20 cytokines, chemokines and growth factors in 14 patients with psoriasis vulgaris at the start and during the course of ultraviolet B treatment. Methods A multiplex cytokine assay was used. Results We identified increased serum levels of epidermal growth factor (EGF) (mean 323 vs. 36·6 pg mL^?1, P =0·0001), interleukin (IL)‐1 receptor antagonist (mean 39·1 vs. 14·6 pg mL^?1, P =0·02) and tumour necrosis factor‐α (mean 7·5 vs. 4·5 pg mL^?1, P =0·04) at baseline in patients with psoriasis compared with matched controls. None of these cytokines was correlated to the severity of the disease (Psoriasis Area and Severity Index) or decreased with phototherapy, suggesting that sources other than lesional skin contribute to the production of these cytokines. Using cluster analysis, we observed coordinate upregulation of EGF, IL‐6, macrophage inflammatory protein‐1β and vascular endothelial growth factor. Conclusions The sustained high expression of inflammatory circulating cytokines is a potential mechanism linking psoriasis with its extracutaneous comorbidities.     

Paraoxonase 1 (PON1) 55 polymorphism,lipid profiles and psoriasis

Background Paraoxonase 1 (PON1) is a serum high‐density lipoprotein‐bound enzyme with antioxidant function. It hydrolyses lipid peroxides, protecting low‐density lipoproteins from oxidative modifications. Patients with psoriasis are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism. Objectives In this study, association of the PON1 55 M allele with serum arylesterase (ARE) activity, malondialdehyde (MDA), lipid profiles and psoriasis was investigated. Methods The present case–control study consisted of 100 patients with psoriasis with and without cardiovascular diseases (mean age 35·3 years) and 100 sex‐ and age‐matched unrelated healthy controls (mean age 35·7 years) from the population of western Iran. The PON1 55 Met>Leu polymorphism was detected by polymerase chain reaction–restriction fragment length polymorphism. Serum ARE activity, MDA, and lipid and apolipoprotein levels were determined spectrophotometrically, by high‐performance liquid chromatography and by enzyme assay, respectively. Results The presence of the PON1 55 M allele was found to be associated with psoriasis (odds ratio = 1·96, P = 0·017). The patients with psoriasis with the PON1 M (M/L + M/M) allele had higher MDA levels (4·12 ± 0·88 vs. 2·24 ± 0·55 μmol L^?1, P < 0·001), apolipoprotein B (APOB)/APOA1 ratio (0·91 ± 0·66 vs. 0·66 ± 0·35, P = 0·004), APOB (111 ± 38·7 vs. 88·3 ± 22·5 mg mL^?1, P = 0·001) and lipoprotein(a) [LP(a)] (21·9 ± 18·4 vs. 15·8 ± 16·6 mg mL^?1, P = 0·034), but lower ARE activity (39·6 ± 11 vs. 45·9 ± 11·8 U mL^?1, P = 0·031) than the control subjects. ARE activity showed a significant positive correlation with APOA1 and a negative correlation with MDA concentration in patients with psoriasis. Conclusions The PON1 55 M allele is a risk factor for psoriasis. Carriers of this allele have high levels of MDA, APOB and LP(a), a high APOB/APOA1 ratio and low ARE activity. These results indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of psoriasis and its related complications. These data suggest that patients with psoriasis are more susceptible to vascular diseases.     

Evidence for vitamin D deficiency and increased prevalence of fractures in autoimmune bullous skin diseases

Background Vitamin D deficiency plays a role in autoimmune diseases and risk of fractures. No data are available on vitamin D levels and vertebral fractures in autoimmune bullous skin diseases. Objectives To assess serum vitamin D levels and the prevalence of vertebral fractures in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), potentially fatal autoimmune bullous disorders. Methods We studied 13 consecutive inpatients with untreated active PV (six men and seven women, mean ± SD age 53·5 ± 14·3 years), 15 with BP (seven men and eight women, mean ± SD age 76·9 ± 12·4 years) and 28 age‐, body mass index‐ and sex‐matched controls. The 25‐hydroxyvitamin D (25‐OHD) levels and presence of vertebral fractures on spinal X‐ray were assessed in all subjects. Results In patients with PV, 25‐OHD levels were lower (mean ± SD 12 ± 4·4 ng mL^?1) and prevalence of severe hypovitaminosis D higher (62%) than in controls (mean ± SD 22·2 ± 11·7 ng mL^?1, P = 0·012; 23%, P = 0·0047, respectively). The prevalence of fractures was 54% and 31% in patients with PV and controls, respectively. Patients with BP showed lower 25‐OHD levels (mean ± SD 9·6 ± 7·2 ng mL^?1) and higher prevalence of severe hypovitaminosis D (73%) than controls (mean ± SD 22·6 ± 18·7 ng mL^?1, P = 0·022; 27%, P = 0·01, respectively). The prevalence of fractures tended to be higher in patients with BP than in controls (67% vs. 33%, respectively, P = 0·068). Conclusions The low 25‐OHD levels found in PV and BP may suggest a role for this agent in their pathogenesis. The increased prevalence of fractures should be taken into consideration in patients who must be given corticosteroids.     

Vitamin D deficiency and rickets in children and adolescents with ichthyosiform erythroderma in type IV and V skin

Background Ichthyosiform erythroderma due to keratinizing disorders may suppress cutaneous vitamin D synthesis, leading to vitamin D deficiency and rickets. Objectives To determine the prevalence of vitamin D deficiency and rickets in children and adolescents with congenital ichthyosis and other keratinizing disorders with erythroderma and scaling. Patients and methods In this cross‐sectional study, 45 children and adolescents with ichthyosiform erythroderma due to keratinizing disorders, and 66 controls (group 1: age and sex matched, with skin diseases other than keratinizing disorders; group 2: age and sex matched, healthy volunteers) were included. Evidence of rickets was determined clinically (physical examination and radiographs) and biochemically {serum calcium, phosphorus, alkaline phosphatase, 25‐hydroxy vitamin D [25(OH)D] and parathyroid hormone (PTH)}. Results All patients in the disease group had clinical, radiological or biochemical evidence of rickets [25(OH)D < 20 ng mL^?1], and analysis was done for all subjects with the available biochemical reports. The mean serum 25(OH)D levels of the disease group was 8·38 ± 5·23 ng mL^?1 and was significantly lower than in control group 1 (11·1 ± 5·8 ng mL^?1) (P < 0·01) and control group 2 (13·5 ± 6·9 ng mL^?1) (P < 0·001). The prevalence of vitamin D deficiency [25(OH)D < 20 ng mL^?1] was significantly higher in the disease group (n = 38 of 39, 97·4%) than in control group 2 (n = 12, 70·6%) (P < 0·01), and total controls (n = 56, 84·8%) (P = 0·04). The frequency of hyperparathyroidism (PTH > 65 pg mL^?1) was also significantly higher in the disease group than in controls (P < 0·01). Conclusions Children and adolescents with various forms of ichthyosiform erythroderma, especially those with pigmented skin (types IV–VI), are at increased risk of developing vitamin D deficiency and clinical rickets.     

Ustekinumab does not increase body mass index in patients with chronic plaque psoriasis: a prospective cohort study

Background Chronic plaque psoriasis is frequently associated with metabolic disorders including obesity. Antitumour necrosis factor α treatments can induce body‐weight increase in patients with psoriasis. Information on the effect of ustekinumab on body weight is not available. Objectives To investigate whether therapy with ustekinumab is associated with changes in body mass index (BMI) in patients with chronic plaque psoriasis. Methods A prospective, multicentre study comparing the changes in BMI in two closed cohorts of patients with psoriasis during 7‐month treatment with ustekinumab (n = 79) or infliximab (n = 83). Results Patients treated for 7 months with infliximab showed a significant (P < 0·001) increase in mean BMI (2·1 ± 4·5%) and body weight (2·5 ± 3·3 kg) compared with patients treated with ustekinumab (0·1 ± 3·3%; 0·6 ± 1·1 kg). Some 45% of patients treated with infliximab had a BMI increase > 2%, compared with only 11% of those receiving ustekinumab (P = 0·01). In the multivariate analysis, all other clinical parameters predicted the BMI increase, except for the use of infliximab. At month 7, 96% of patients treated with infliximab and 82% of patients treated with ustekinumab achieved at least a 50% improvement from their baseline psoriasis area and severity index (PASI 50), and 69% of the infliximab group compared with 58% of the ustekinumab group achieved at least PASI 75. There was no difference in the proportion of PASI 50 and PASI 75 responders between the two groups. Conclusions In contrast to infliximab, ustekinumab does not increase BMI in patients with chronic plaque psoriasis. This difference could be taken into account in the selection of biologics when treating patients with psoriasis.     

CCL13 is a promising diagnostic marker for systemic sclerosis

Background Previous studies suggest that CCL13 may have some role in the pathogenesis of systemic sclerosis (SSc). Objectives To determine serum levels of CCL13 and its clinical associations in patients with SSc. Methods Serum CCL13 levels were examined by enzyme‐linked immunosorbent assay in 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), 20 patients with dermatomyositis (DM), 29 patients with atopic dermatitis (AD) and 50 healthy individuals. Results Mean ± SD serum CCL13 levels were elevated in patients with SSc (81·3 ± 55·8 pg mL^?1) compared with healthy controls (15·0 ± 9·9 pg mL^?1; P < 0·001) and patients with SLE (22·0 ± 6·9 pg mL^?1; P < 0·001), DM (24·4 ± 36·1 pg mL^?1; P < 0·001) and AD (18·0 ± 6·4 pg mL^?1; P < 0·001). Among patients with SSc, there were no differences in serum CCL13 levels between limited cutaneous SSc and diffuse cutaneous SSc. In a longitudinal study, CCL13 levels were generally unchanged during the follow‐up. Conclusions Serum CCL13 was specifically increased in patients with SSc, but not in patients with SLE, DM or AD or in healthy controls. CCL13 could be a promising serological marker for SSc.     

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial

Background Psoriasis is a chronic disease that significantly diminishes the health‐related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor α monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods In this double‐blind, placebo‐controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg^?1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3‐ and 5‐mg kg^?1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg^?1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty‐three per cent and 40% of patients in the 3 and 5 mg kg^?1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50–75% improvement in PASI during the same period (60%). Conclusions Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.     

Plasma homocysteine and folate levels in patients with chronic plaque psoriasis

Background Hyperhomocysteinaemia is a well‐known risk factor for cardiovascular diseases. Patients with severe chronic plaque psoriasis have a higher risk of death due to arterial and/or venous thrombosis. Objectives To investigate the relationship among plasma homocysteine and folate levels and severity of chronic plaque psoriasis in a selected cohort of patients with psoriasis without known risk factors for acquired hyperhomocysteinaemia. Methods We performed a case–control study in 40 patients with chronic plaque psoriasis and 30 age‐ and sex‐matched healthy controls. Cases and controls were selected excluding individuals with conditions or diseases associated with acquired hyperhomocysteinaemia, and were also asked to stop alcohol and coffee consumption for 1 week before blood sampling. The plasma levels of homocysteine and folic acid were measured and were correlated with the severity of psoriasis (Psoriasis Area and Severity Index, PASI). Results Patients with psoriasis had plasma homocysteine levels higher than controls (mean ± SD 16·0 ± 5·6 vs. 10·4 ± 4·7 μmol L^?1; P < 0·001). Conversely, folic acid levels were lower in patients with psoriasis compared with controls (mean ± SD 3·6 ± 1·7 vs. 6·5 ± 1·7 nmol L^?1; P < 0·001). Plasma homocysteine levels in patients with psoriasis correlated directly with disease severity (PASI) and inversely with folic acid levels. Plasma folic acid levels were inversely correlated with the PASI. No abnormalities of plasma vitamin B₆ and B₁₂ were found. Conclusions Patients with psoriasis may have a tendency to hyperhomocysteinaemia, which may predispose to higher cardiovascular risk. Dietary modification of this risk factor appears relevant to the global management of patients with moderate to severe psoriasis.     

Serum leptin concentration is increased in patients with Behçet's syndrome and is correlated with disease activity

Summary Background Behçet's syndrome is a systemic, relapsing immuno‐inflammatory disease with a generalized vasculitis of the microvasculature endothelial dysfunction. Leptin, a recently discovered neuroendocrine hormone, is a metabolic peptide that appears to be involved. Serum proinflammatory cytokines upregulate leptin levels and leptin itself directly induces nitric oxide production from endothelial cells with its specific receptors. Objectives To detect changes of serum leptin concentrations in patients with Behçet's syndrome compared with age‐ and sex‐matched healthy volunteers by using enzyme‐linked immunosorbent assay. We also investigated whether disease activity or the duration of Behçet's syndrome correlates with leptin concentration. Methods Thirty‐five consecutive patients with Behçet's syndrome (41·2 ± 8·4 years, 16 male, 19 female) and 20 age‐ and sex‐matched healthy control subjects (40·4 ± 10·91 years, nine male, 11 female) were included in this study. The body mass index (BMI) [weight (kg) height^?1 (m²)] was calculated for subjects at study enrolment. We measured serum leptin with a leptin enzyme immunoassay kit, and acute‐phase reactants, including erythrocyte sedimentation rate, α₁‐antitrypsin, α₂‐macroglobulin and neutrophil count. The Mann–Whitney U‐test was used for statistical analysis and P < 0·05 was considered significant. Values were expressed as mean ± SD. Results The gender ratio, age and BMI were not substantially different among Behçet's patients and controls. The mean serum leptin concentrations in patients with Behçet's syndrome (16·8 ± 7·49 ng mL^?1) were significantly (P < 0·001) higher than in healthy control volunteers (7·5 ± 2·77 ng mL^?1). Active Behçet's patients had significantly (P = 0·001) higher leptin concentrations (20·5 ± 7·99 ng mL^?1) when compared with patients in inactive periods (12·8 ± 4·43 ng mL^?1). In addition, patients with longer disease duration (mean, 20·1 ± 5·15 years) had also significantly (P = 0·013) higher leptin concentrations (20·2 ± 8·52 ng mL^?1) than those with shorter disease duration (13·4 ± 4·52 ng mL^?1) (mean, 7·4 ± 3·29 years). All acute‐phase reaction parameters were found to be significantly (for each, P < 0·01) increased in active disease. Conclusions Leptinmay have a role in modulating endothelial function and may be involved in mechanisms for vessel endothelium repair, during an exacerbation as well as in chronic disease.     

Evaluation of zinc level in skin of patients with necrolytic acral erythema

Summary Background Necrolytic acral erythema (NAE) is considered a cutaneous sign of hepatitis C virus infection. Its exact pathogenesis is still not fully understood, with some reports about decreased serum zinc levels but none about its level in the skin. Objectives To assess skin (lesional and perilesional) and serum zinc levels in patients with NAE and compare them with levels in control subjects. Methods Fifteen patients with NAE and 10 healthy controls were included in this study. Assessment of zinc level, in serum by graphite furnace atomic absorption spectrophotometry and in lesional and perilesional skin biopsies by flame atomic absorption spectrometry, was done in all subjects. Re‐evaluation of serum and lesional skin zinc level was done after oral zinc treatment. Results Mean ± SD zinc levels were significantly lower in patients (serum 0·44 ± 0·13 mg L^?1; lesional skin 42·6 ± 18·9 mg L^?1; perilesional skin 32·5 ± 17·2 mg L^?1) than controls (serum 1·17 ± 0·29 mg L^?1; skin 100·1 ± 2·77 mg L^?1), with a positive correlation between lesional and perilesional skin zinc (r = 0·91, P < 0·01). Oral zinc supplementation significantly increased serum and skin zinc levels (by 159% and 4%, respectively; P < 0·05). Conclusions NAE is associated with decreased serum and skin zinc levels. Oral zinc supplementation corrects decreased levels of plasma and skin zinc much earlier than the desired clinical benefits appear.     

Correlation between serum 25‐hydroxyvitamin D levels and severity of atopic dermatitis in children

Background Vitamin D deficiency could be associated with the prevalence of atopic dermatitis (AD). Objectives We carried out a study to see whether deficient/insufficient levels of vitamin D correlate with the severity of atopic skin disease. Methods Using the SCORAD index, we evaluated the severity of disease in 37 children (17 girls and 20 boys) aged between 8 months and 12 years with AD, consecutively enrolled in the study. Serum levels of 25‐hydroxyvitamin D [25(OH)D] were determined by a chemiluminescent method. Specific IgE (sIgE) to Staphylococcus aureus enterotoxins and sIgE to Malassezia furfur were assayed by the ImmunoCAP system. anova and the Pearson correlation test were used for statistical evaluation. Results We found severe, moderate and mild AD in nine (24%), 13 (35%) and 15 (41%) children, respectively. Mean ± SD serum levels of 25(OH)D were significantly higher (P < 0·05) in patients with mild disease (36·9 ± 15·7 ng mL^?1) compared with those with moderate (27·5 ± 8·3 ng mL^?1) or severe AD (20·5 ± 5·9 ng mL^?1). The prevalence of patients with sIgE to microbial antigens increased in relation to vitamin D deficiency and AD severity. Conclusions These data suggest that vitamin D deficiency may be related to the severity of AD and advocate the need for studies evaluating the use of vitamin D as a potential treatment in patients with this disease.     

Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial

Background Previous epidemiological, animal and human data report that lycopene has a protective effect against ultraviolet radiation (UVR)‐induced erythema. Objectives We examined whether tomato paste – rich in lycopene, a powerful antioxidant – can protect human skin against UVR‐induced effects partially mediated by oxidative stress, i.e. erythema, matrix changes and mitochondrial DNA (mtDNA) damage. Methods In a randomized controlled study, 20 healthy women (median age 33 years, range 21–47; phototype I/II) ingested 55 g tomato paste (16 mg lycopene) in olive oil, or olive oil alone, daily for 12 weeks. Pre‐ and postsupplementation, UVR erythemal sensitivity was assessed visually as the minimal erythema dose (MED) and quantified with a reflectance instrument. Biopsies were taken from unexposed and UVR‐exposed (3 × MED 24 h earlier) buttock skin pre‐ and postsupplementation, and analysed immunohistochemically for procollagen (pC) I, fibrillin‐1 and matrix metalloproteinase (MMP)‐1, and by quantitative polymerase chain reaction for mtDNA 3895‐bp deletion. Results Mean ± SD erythemal D₃₀ was significantly higher following tomato paste vs. control (baseline, 26·5 ± 7·5 mJ cm^?2; control, 23 ± 6·6 mJ cm^?2; tomato paste, 36·6 ± 14·7 mJ cm^?2; P = 0·03), while the MED was not significantly different between groups (baseline, 35·1 ± 9·9 mJ cm^?2; control, 32·6 ± 9·6 mJ cm^?2; tomato paste, 42·2 ± 11·3 mJ cm^?2). Presupplementation, UVR induced an increase in MMP‐1 (P = 0·01) and a reduction in fibrillin‐1 (P = 0·03). Postsupplementation, UVR‐induced MMP‐1 was reduced in the tomato paste vs. control group (P = 0·04), while the UVR‐induced reduction in fibrillin‐1 was similarly abrogated in both groups, and an increase in pCI deposition was seen following tomato paste (P = 0·05). mtDNA 3895‐bp deletion following 3 × MED UVR was significantly reduced postsupplementation with tomato paste (P = 0·01). Conclusions Tomato paste containing lycopene provides protection against acute and potentially longer‐term aspects of photodamage.     

25-Hydroxyvitamin D levels in African-American and Caucasian/Hispanic subjects with cutaneous lupus erythematosus

Background Because exposure to ultraviolet radiation accounts for a significant portion of endogenous vitamin D production, subjects with cutaneous lupus (CLE) who practise sun‐protective measures are at risk for vitamin D insufficiency. Previous studies have shown light‐skinned subjects with CLE to have lower serum 25‐hydroxy (25‐OH) vitamin D levels than normal controls. Objectives To assess the status of vitamin D insufficiency in dark‐skinned individuals with CLE. Methods We performed a cross‐sectional study comparing serum 25‐OH vitamin D levels in 25 African‐American (AA) subjects with CLE and 26 normal AA subjects matched by age, sex and season in Dallas, Texas. A questionnaire on demographics, medical history and lifestyle habits was administered to determine factors potentially affecting vitamin D levels. Findings were contrasted to a similar comparison in 26 Caucasian and Hispanic (C/H) subjects with CLE and 24 normal C/H subjects matched by age, sex and season. Results We found similar mean ± SD 25‐OH vitamin D levels in AA subjects with CLE (52·0 ± 18·5 nmol L^?1) and normal AA subjects (54·8 ± 21·2 nmol L^?1) (P = 0·62). Almost half of AA subjects in both groups were vitamin D insufficient. A larger difference in 25‐OH vitamin D levels was found between C/H subjects with CLE (59·4 ± 21·0 nmol L^?1) and normal C/H subjects (70·5 ± 27·4 nmol L^?1) (P = 0·12). Two‐way anova demonstrated that skin colour (AA vs. C/H) had a significant effect on 25‐OH vitamin D levels (P = 0·008), although CLE status (CLE vs. normal) did not (P = 0·13). Conclusions Providers are encouraged to address vitamin D insufficiency concerns in all dark‐skinned individuals. Future studies should stratify subjects by skin colour in determining differences between subjects with CLE and normal controls.     

Activation of blood coagulation in bullous pemphigoid: role of eosinophils, and local and systemic implications

Background Bullous pemphigoid (BP) is a blistering skin disease caused by autoantibodies to hemidesmosomal proteins, with eosinophils participating in blister formation. Eosinophils are a source of tissue factor (TF), an initiator of blood coagulation. Objectives To evaluate the local and systemic activation of coagulation in BP. Methods We studied 20 patients with active BP (eight re‐evaluated during remission) and 40 controls. The coagulation markers prothrombin fragment F1+2 and d ‐dimer were measured in the plasma of all subjects and in both plasma and blister fluid of patients with BP. TF was evaluated immunohistochemically in skin specimens from the 20 patients and in 20 normal samples. Results F1+2 and d ‐dimer levels were higher in plasma of patients with BP (649 ± 96 pmol L^?1 and 18·52 ± 3·44 nmol L^?1, respectively) than in plasma of controls (157 ± 7 pmol L^?1 and 1·42 ± 0·06 nmol L^?1; P = 0·0001), and were very high in blister fluid (40 449 ± 3491 pmol L^?1 and 1532·32 ± 262·81 nmol L^?1; P = 0·0001). Plasma and blister fluid F1+2 and d ‐dimer levels paralleled blood and tissue eosinophilia and disease severity. In the eight patients re‐evaluated during remission, there was a marked reduction in F1+2 (from 1127 ± 144 to 287 ± 52 pmol L^?1; P = 0·005) and d ‐dimer (from 24·03 ± 4·08 to 4·69 ± 1·51 nmol L^?1; P = 0·029). Immunohistochemistry revealed strong TF reactivity in BP skin (P = 0·0001), and colocalization studies confirmed eosinophils as a source of TF. Conclusions The coagulation cascade is activated in BP and correlates with the severity of the disease and with eosinophilia, indicating that eosinophils play a role in coagulation activation via TF. The hypercoagulability may contribute to inflammation, tissue damage, blister formation and possibly thrombotic risk in BP.     

Vitamin D status in patients with chronic plaque psoriasis

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 (P < 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 (P < 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.     

Serum 25‐hydroxyvitamin D serum levels in a large German cohort of patients with melanoma

Background Observational studies have suggested that 25‐hydroxyvitamin D [25(OH)D] is associated with better outcomes in patients with malignant melanoma (MM). Objectives To study the relationship between serum 25(OH)D levels and clinical parameters in a large German cohort of patients with MM. Methods We prospectively investigated the 25(OH)D serum levels of 764 patients with MM using the direct competitive chemiluminescence LIAISON^® immunoassay. Patients with MM who were taking 25(OH)D supplements were not included. Results Median serum 25(OH)D baseline levels were 12·3 ng mL^?1 (lower quartile: 7·3 ng mL^?1, upper quartile: 20·2 ng mL^?1). Of the 764 patients, 564 (73·8%) had 25(OH)D deficiency [25(OH)D < 20 ng mL^?1], 145 (18·8%) had 25(OH)D insufficiency [25(OH)D ≥ 20, < 30 ng mL^?1] and only 55 (7·2%) had serum 25(OH)D levels within the normal range (≥ 30 ng mL^?1). Using a multiple regression model, lower 25(OH)D levels were significantly associated with higher Breslow tumour thickness (class: < 1 mm; 1–4 mm; > 4 mm, regression coefficient ?1·45, P = 0·028) and higher American Joint Committee on Cancer 2002 melanoma stage (regression coefficient: ?0·79, P = 0·036). Conclusions In patients with MM, decreased 25(OH)D serum levels are associated with increased tumour thickness and advanced tumour stage. Hence, evidence is accumulating that patients with MM might benefit from 25(OH)D supplements.     

A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial

Background There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance. Objectives To compare the efficacy and safety of a new, once‐daily, two‐compound scalp formulation (Xamiol^®; LEO Pharma A/S, Ballerup, Denmark) containing calcipotriol 50 μg g^?1 plus betamethasone 0·5 mg g^?1 (as dipropionate), with the active ingredients as single compounds in the same vehicle. Methods This 8‐week, multicentre, double‐blind, parallel‐group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the two‐compound scalp formulation (n = 568), betamethasone dipropionate 0·5 mg g^?1 (n = 563), or calcipotriol 50 μg g^?1 (n = 286). The primary efficacy measure was the proportion of patients with ‘absence of disease’ or ‘very mild disease’ according to investigators’ assessments at week 8. Results The proportion of patients with ‘absence of disease’ or ‘very mild disease’ at week 8 was significantly higher in the two‐compound group (68·4%) than the betamethasone dipropionate (61·0%, P = 0·0079) or calcipotriol (43·4%, P < 0·0001) groups. The proportion of patients rating their scalp psoriasis as ‘clear’ or ‘almost clear’ was significantly higher for the two‐compound scalp formulation (69·6%) than for betamethasone dipropionate (59·9%, P = 0·0006) or calcipotriol (44·7%, P < 0·0001). The incidence of lesional/perilesional adverse events was lower in the two‐compound and betamethasone dipropionate groups than the calcipotriol group. Conclusions The two‐compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle.     

Paediatric-onset psoriasis is associated with ERAP1 and IL23R loci, LCE3C_LCE3B deletion and HLA-C*06

Summary Background Recent genome‐wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking. Objectives To compare the association between known risk alleles and psoriasis in well‐defined cohorts with paediatric‐ and adult‐onset psoriasis. Methods Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric‐onset (< 18 years) and adult‐onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85). Results Paediatric‐onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0·042) and IL23R loci (P = 0·042), LCE3C_LCE3B‐del (P = 0·003) and HLA‐C*06 (P = 1·72 × 10^?19) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult‐onset psoriasis a significant association was found for HLA‐C*06 (P = 5·11 × 10^?6) and for LCE3C_LCE3B‐del (P = 0·042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci. Conclusions Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric‐onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric‐onset psoriasis than in adult‐onset psoriasis.