Histamine release in skin monitored with the microdialysis technique does not correlate with the weal size induced by cow allergen

Summary The purpose of this study was to monitor histamine release in immediate-type hypersensitivity reactions in the skin of 10 atopic patients, sensitive to cow, by using the microdialysis technique. Three healthy subjects, without any atopic features or background, served as the control group. The probe inserted into the forearm dermal skin was perfused with isotonic saline solution. Samples were collected at 15-min intervals. After the first allergen challenge of four prick tests close to the probe with cow allergen extract, the skin was similarly repricked again in five patients and three healthy subjects, and in five other patients, 25μl of 10μmol/l substance P (SP) was injected intracutaneously. The samples were analysed for histamine by radioenzyme assay. The patients were clinically evaluated for allergic symptoms, prick- and scratch-patch test reactivity and for serum cow-specific, and total, IgE levels. The baseline histamine concentration was 7·5±4·0 nmol/l (mean±standard deviation: SD; n=10). After the allergen challenge, the histamine concentration in the consecutive samples was 11·9±11·0 nmol/l, 91·1±127·3 nmol/l, 61·0±94·2 nmol/l and 33·7±53·7 nmol/l. The peak concentration was detected in the 15–30 min fraction, and it varied between 0 and 406 nmol/l regardless of the weal size. The second allergen challenge was unable to induce marked additional histamine release, but SP induced extensive histamine liberation in those patients who did not exhibit histamine release during the preceding prick tests. In three healthy subjects, the baseline histamine concentration was 6·2±3·9 nmol/l. After the allergen challenge, no additional histamine liberation could be measured. Surprisingly, the histamine release was not related to the size of the cow-induced weal nor was it related to any specific allergic symptoms or IgE levels. The results suggest that, in some patients, mast cell mediators other than histamine play a significant part in immediate-type allergic reactions of skin.     

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.     

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.     

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.     

Superiority of tacrolimus 0·1% ointment compared with fluticasone 0·005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double-blind trial

Summary Background No specific data are available on tacrolimus ointment as a second‐line treatment in adults with facial eczema. Objectives To compare tacrolimus 0·1% and fluticasone 0·005% ointments in adults with moderate to severe atopic dermatitis (AD) of the face in whom conventional treatment was ineffective or poorly tolerated. Methods Patients were randomized to double‐blind treatment of facial AD with twice‐daily tacrolimus ointment (n = 288) or fluticasone ointment (n = 280) for 3 weeks or until clearance. After day 21, patients could continue without the study treatment, apply the same ointment once daily, or switch to the other medication twice daily, depending on lesion clearance and patient/physician satisfaction. The primary endpoint was the day‐21 response [≥ 60% reduction in the modified Local Eczema and Severity Index (mLEASI) score]. Secondary endpoints included facial erythema and pruritus, global clinical response, treatment switching at day 21 and safety. Results Response with tacrolimus ointment (93%) was superior to that with fluticasone (88%; P = 0·026). Improvements in mLEASI components were also greater with tacrolimus ointment. Facial erythema and pruritus improved in both groups. Global clinical response was rated ‘marked improvement’ or better in 88% and 79% of patients in the tacrolimus ointment and fluticasone groups, respectively. At day 21, 9% of patients switched from fluticasone to tacrolimus ointment, while 4·5% switched from tacrolimus ointment to fluticasone. Adverse events were more frequent with tacrolimus ointment as a result of the higher incidence of application‐site skin burning sensation. Safety of both drugs was in line with their respective summary of product characteristics. Conclusions Tacrolimus 0·1% ointment has superior efficacy to fluticasone 0·005% ointment for twice‐daily treatment of adults with moderate to severe facial AD in whom conventional therapy was inadequately effective or not tolerated. Tacrolimus 0·1% ointment is a safe and effective second‐line treatment for the control of moderate to severe AD of the face.     

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.     

The influence of nitric oxide synthase 2 on cutaneous wound angiogenesis

Background Inducible nitric oxide synthase (nitric oxide synthase 2, NOS 2) inhibition significantly suppresses chronically ischaemic skin flap survival, possibly because of reduced angiogenesis. Objectives To investigate the effect of genetic NOS 2 inhibition on cutaneous wound angiogenesis in two in vivo murine models. The impact of NOS 2 manipulation on vascular endothelial growth factor (VEGF)‐A stimulated and fibroblast growth factor (FGF)‐2 stimulated angiogenesis was also investigated in the Matrigel^® plug assay. Methods (i) Matrigel plugs/incisional wounds: two groups of NOS 2?/? mice and two groups of wild‐type (WT) mice had bilateral Matrigel plugs containing 500 ng mL^?1 VEGF‐A or 1000 ng mL^?1 FGF‐2 injected subcutaneously in the abdomen. A 2·5 cm long dorsal incisional skin wound was created and sutured closed in the same animals. Wounds and plugs were explored at 7 or 12 days. (ii) Excisional wounds: dorsal 0·5 × 1·0 cm excisional skin wounds were created in four groups (two NOS 2?/? and two WT) and explored at 7 or 14 days. Wounds and Matrigel plugs were examined histologically and morphometrically for determination of percentage vascular volume (PVV). Results The PVV in NOS 2?/? incisional wounds and excisional wounds was significantly less than in WT wounds (P = 0·05 and P < 0·001, respectively). The PVV was significantly less in VEGF‐A stimulated Matrigel plugs compared with FGF‐2 stimulated plugs in NOS 2?/? mice (P < 0·01), but not in WT mice. Conclusions NOS 2 is significantly involved in angiogenic signalling in healing skin wounds, particularly within the first 7 days. However, Matrigel plug vascularization suggests that the role of NOS 2 in angiogenesis is related to VEGF‐A but not FGF‐2 stimulated angiogenesis.     

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.     

Enhancing effect of pretreatment with topical niacin in the treatment of rosacea‐associated erythema by 585‐nm pulsed dye laser in Koreans: a randomized,prospective, split‐face trial

Background Rosacea is a chronic dermatosis that is usually confined to the face. A pulsed dye laser (PDL) system has been proven to be effective in treating rosacea‐associated erythema and telangiectasias. Niacin is a cutaneous vasodilator that can increase the chromophore through increased blood flow. Objectives We hypothesized that increased blood flow by pretreatment with topical niacin could enhance the effect of PDL in the treatment of rosacea. Methods Eighteen Korean patients with rosacea were recruited. Three sessions of 585‐nm PDL using a subpurpuragenic dose with and without pretreatment with niacin cream were performed on randomly assigned half‐faces at 3‐week intervals. Erythema was assessed objectively by a polarization colour imaging system, and evaluations were also made by three blinded dermatologists. Patient satisfaction was evaluated using a 10‐point visual analogue scale. Results Fifteen patients completed this study. All patients showed an improvement in erythema after three sessions of PDL treatment both with and without niacin pretreatment (P = 0·023 and P = 0·009, respectively). There was no significant difference in the improvement of objective erythema between the two sides. However, based on physician assessment the overall clinical improvement on the niacin side was significantly higher (P = 0·005), and patient satisfaction was also higher on the niacin‐pretreated side (P = 0·007). There were no remarkable side‐effects, with the exception of transient erythema and oedema. Conclusions Pretreatment with topical niacin safely enhanced the effect of 585‐nm PDL treatment of rosacea‐associated erythema in Koreans. Application of niacin can be helpful in overcoming the relatively lower effect of subpurpuragenic PDL in dark‐skinned Asians.     

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.     

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.     

Can St John's wort (hypericin) ingestion enhance the erythemal response during high‐dose ultraviolet A1 therapy?

Background St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high‐dose UVA1 therapy. Objectives To assess the phototoxicity risk of SJW ingestion. Methods Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high‐output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70–77 mW cm^?2) on the photoprotected lower back skin at eight 1·5‐cm² test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 µg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter. Results The median MED and D_0·025, an objective measure of MED, were lower at all time‐points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm^?2, range 10–56) than at baseline (median 20 J cm^?2, range 14–56) (P = 0·047). Similarly, the median D_0·025 at 8 h postirradiation was lower after SJW (median 22·0 J cm^?2, range 15·2–53·9) than at baseline (median 33·7 J cm^?2, range 22·9–136·0) (P = 0·014). The MED and D_0·025 were also significantly different at the 48‐h and 4‐h time‐points, respectively. Significance was not reached at the 24‐h time‐point. Median intensity of postirradiation erythema increased at all time‐points after ingestion of SJW. Despite these differences, the maximum slope of the dose–response curve was not increased after SJW ingestion. Conclusions These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.     

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.     

Contralateral distribution of nonmelanoma skin cancer between older Hispanic/Latino and non‐Hispanic/non‐Latino individuals

Background A recent review of the SEER database revealed that melanoma and Merkel cell carcinoma occur more commonly on the left side of the body. Similarly, a trend was reported in which nonmelanoma skin cancers (NMSCs) were found to be distributed more frequently on the left side of the body. Objectives To compare the sidedness of NMSC in a large patient population. There were five primary objectives of the present study: (i) to confirm or refute the left‐sided trend of NMSC in the largest patient population studied for asymmetry to date; (ii) to determine whether the left‐sided trend existed in Hispanic/Latino individuals; (iii) to examine skin cancer in older individuals across ethnicities; (iv) to compare distribution across anatomical location and ethnicity; and (v) to measure gender differences in the distribution of NMSC. Methods The last 3026 cases referred to the Mohs surgical unit at the University of Miami Miller School of Medicine during 2008–2011 were reviewed. The patient’s age, gender, tumour side, tumour type, anatomical location and ethnicity were recorded. Results There were 1505 (50·2%) right‐sided tumours and 1495 (49·8%) left‐sided tumours (P = 0·52). The Hispanic/Latino group had a nonsignificant right‐sided trend with 607 (52·7%) right‐sided cases and 545 (47·3%) left‐sided cases (P = 0·06). The non‐Hispanic/non‐Latino group between the ages of 60 and 85 years had 605 (46·9%) right‐sided tumours and 686 (53·1%) left‐sided tumours (P = 0·024). The Hispanic/Latino group between the ages of 60 and 85 years demonstrated 404 (54·0%) right‐sided tumours and 344 (46·0%) left‐sided tumours (P = 0·028). One hundred and fifty‐four skin cancers were located on the upper extremities of non‐Hispanic/non‐Latino individuals with 64 (41·6%) being right sided and 90 (58·4%) left sided (P = 0·036). Seventy‐eight skin cancers were located on the upper extremities of Hispanic/Latino individuals with 49 (62·8%) being right sided and 29 (37·2%) left sided (P = 0·024). Males had most of the skin cancers at 2125 (70·8%) cases and females had 875 (29·2%) cases (P < 0·001). Conclusions NMSC appears to be more common on the left side of older non‐Hispanic/non‐Latino individuals, while it is more common on the right side of older Hispanic/Latino individuals. This is likely to be secondary to an environmental factor, such as ultraviolet radiation. NMSC is significantly more common in males relative to females, which may be attributed to differences in gender roles or referral practices.     

Central centrifugal cicatricial alopecia severity is associated with cowhage‐induced itch

Background Patients with central centrifugal cicatricial alopecia (CCCA) often suffer from varying degrees of itch, pain and burning sensations. However, the neural component of these skin sensations has not been assessed. Objective To conduct a comprehensive analysis of C nerve fibre function relating to itch and pain perception in patients with CCCA using thermosensory testing and experimental itch models. Methods Fifteen healthy African‐American women and 16 African‐American female patients with CCCA participated in the study and underwent quantitative computerized thermosensory testing to assess warmth and heat pain thresholds. Itch was induced using histamine iontophoresis and application of cowhage spicules, and the intensity of each itch was assessed. The association between itch intensity and CCCA severity score was examined. Results A positive correlation between CCCA severity score and peak itch ratings of cowhage on the lesional scalp (crown) was observed (P = 0·023, r = 0·562). Notably, the histamine peak itch rating was not found to have a significant correlation with CCCA severity score (P = 0·913). The crown also had significantly higher warmth and pain thresholds than the occiput in both healthy subjects and patients with CCCA. Conclusions Our results suggest a putative role for the protease‐activated receptor (PAR)‐2, which is activated by cowhage, in the pathogenesis of CCCA. Future studies should examine PAR‐2‐directed therapeutics for patients with CCCA. Examining for itch and other dysaesthesias in patients with CCCA is of vital importance to dermatologists in assessing disease severity.     

Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial

Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field‐cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. Objectives To evaluate efficacy and safety of AFXL‐assisted PDT (AFXL‐PDT) compared with conventional PDT in field‐directed treatment of AK. Methods Fifteen patients with a total of 212 AKs (severity grade I–III) in field‐cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL‐PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0·12 mm spot, 5% density, single pulse (UltraPulse^®, DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U.S.A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light‐emitting diode light at 37 J cm^?2. Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. Results At 3‐month follow‐up, AFXL‐PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II–III AK was 88% after AFXL‐PDT compared with 59% after PDT (P = 0·02). In grade I AK, 100% of lesions cleared after AFXL‐PDT compared with 80% after PDT (P = 0·04). AFXL‐PDT‐treated skin responded with significantly fewer new AK lesions (AFXL‐PDT n = 3, PDT n = 11; P = 0·04) and more improved photoageing (moderate vs. minor improvement, P = 0·007) than PDT‐treated skin. Pain scores during illumination (6·5 vs. 5·4; P = 0·02), erythema and crusting were more intense, and long‐term pigmentary changes more frequent from AFXL‐PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL‐pretreated skin [7528 vs. 12 816 arbitrary units (AU); P = 0·003] and photobleached to equal intensities after illumination (AFXL‐PDT 595 AU, PDT 454 AU; P = 0·59). Conclusions AFXL‐PDT is more effective than conventional PDT for treatment of AK in field‐cancerized skin.     

Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration

Summary Background A short course of narrowband ultraviolet B (NB‐UVB) exposures increases the serum 25‐hydroxyvitamin D [25(OH)D] concentration in patients with psoriasis and healthy subjects. Objectives To compare the effects of NB‐UVB and oral vitamin D substitution in healthy subjects in winter. Methods Healthy adult hospital employees and medical students were screened for serum 25(OH)D concentration. Those with 25(OH)D below 75 nmol L^?1 were randomly given either 12 NB‐UVB exposures or 20 μg of oral cholecalciferol daily for 4 weeks. The NB‐UVB exposures were given with a Waldmann UV 7001 cabin and the mean cumulative dose was 48·4 standard erythema doses. Serum 25(OH)D was measured before and after the treatments by radioimmunoassay. Results The baseline serum 25(OH)D concentrations were 52·9 ± 10·4 (mean ± SD) in the 33 NB‐UVB‐treated and 53·5 ± 12·7 nmol L^?1 in the 30 oral cholecalciferol‐treated subjects. The mean increase in serum 25(OH)D was 41·0 nmol L^?1 [95% confidence interval (CI) 34·8–47·2; P < 0·001] in the NB‐UVB group and 20·2 nmol L^?1 (95% CI 14·6–26·0; P < 0·001) in the cholecalciferol group. The difference between the two treatments was significant at 2 weeks (P = 0·033) and at 4 weeks (P < 0·001). One month after the treatments the 25(OH)D concentrations had increased further. Conclusions The present study shows that 12 NB‐UVB exposures given during 4 weeks increase serum 25(OH)D concentration significantly more than 20 μg of oral cholecalciferol daily. A short NB‐UVB course is an effective way to improve vitamin D balance in winter and the response is still evident 2 months after the course.     

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.     

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.