Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis

Background Atopic dermatitis (AD) is a chronic skin disease affecting more than 15% of children and 2% of adults. A strong connection between genetic factors and AD has been described for a long time. Histamine receptor H4 (HRH4) has been shown to be related to different kinds of allergic and autoimmune disorders. However, an association between HRH4 and AD has not yet been reported. Objectives To examine a possible association between HRH4 and AD. Methods Genomic DNA from 301 patients with AD and 313 healthy controls was extracted and three exons of HRH4 were sequenced. Results We found three new single nucleotide polymorphisms (SNPs) in HRH4 which were significantly associated with AD: ss142022671 [odds ratio (OR) 1·87, 95% confidence interval (CI) 1·24–2·81; P = 0·002], ss142022677 (OR 4·40, 95% CI 2·42–8·00; P = 1·5 × 10^?7) and ss142022679 (OR 4·26, 95% CI 2·38–7·61; P = 1·3 × 10^?7). The SNPs ss142022677 and ss142022679 were found to be in strong linkage disequilibrium (D’ = 0·98; r² = 0·92). Two‐SNP haplotype analysis (ss142022677 and ss142022679) showed that the major AA haplotype was protective against AD (OR 0·22, 95% CI 0·12–0·40; P = 3·1 × 10^?8) and the minor TT haplotype was significantly associated with AD (OR 4·13, 95% CI 2·27–7·54; P = 6·6 × 10^?7). In addition, in a three‐SNP haplotype analysis (ss142022671, ss142022677 and ss142022679), the major TAA haplotype was protective against AD (OR 0·46, 95% CI 0·31–0·69; P = 0·0001), while the complementary ATT haplotype was found to be significantly associated with AD (OR 3·81, 95% CI 2·03–7·14; P = 8·3 × 10^?6). Conclusions Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD.     

Comparison of the two techniques for measurement of the density of Demodex folliculorum: standardized skin surface biopsy and direct microscopic examination

Background In daily dermatological practice, many dermatologists do not include demodicosis in their differential diagnoses, or the diagnosis of demodicosis is frequently masked by other skin diseases such as papulopustular or erythematotelangiectatic rosacea, seborrhoeic dermatitis, perioral dermatitis and contact dermatitis. There are two methods for measurement of the density of Demodex folliculorum (Dd): standardized skin surface biopsy (SSSB) and direct microscopic examination of fresh secretions from sebaceous glands (DME). No study has been reported in the literature comparing the diagnostic value of these two techniques. Objectives To compare the value of the two techniques, SSSB and DME, for the measurement of Dd in patients with suspected demodicosis. Methods Mite density was investigated using SSSB and DME in 37 patients with facial skin lesions suggesting demodicosis. Two samples, one for SSSB and one for DME, were obtained from a cheek lesion of each patient. Results Twenty‐three (62%) patients were diagnosed with demodicosis according to their clinical manifestations combined with a high Dd (Dd > 5 mites cm^?2) with SSSB and/or DME. In all the patients, the mean Dd measured with SSSB was higher than that with DME (22·9 ± 5·9 and 2·2 ± 0·8, respectively; P = 0·001). Also, among the 23 patients with demodicosis, the mean Dd measured using SSSB was higher than the mean Dd with DME (36·5 ± 8·3 and 3·4 ± 1·2, respectively; P = 0·0001). Conclusions We recommend the use of SSSB for the measurement of Dd as more patients with demodicosis can be diagnosed with this method compared with the DME method.     

Filaggrin polymorphism P478S, IgE level, and atopic phenotypes

Background Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. Objectives To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. Methods In total, 116 children aged 2–5 years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. Results A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88–11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37–16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01–10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93–16·60) in children with IgE level ≥ 100 kU L^?1. However, the association was not evident when IgE level was < 100 kU L^?1. Conclusions Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.     

Periorbital dermatitis--a recalcitrant disease: causes and differential diagnoses

Background Periorbital dermatitis is common and frequently recalcitrant to treatment. Due to the exposed and visible location, patients often suffer severely from periorbital dermatitis. Objectives To determine the frequency and causes of periorbital dermatitis including contact sensitizers. Methods We investigated two cohorts of patients (Erlangen and IVDK without Erlangen) between 1999 and 2004. Results The differences between the two cohorts with periorbital dermatitis [Department of Dermatology at University Hospital Erlangen (n = 88) and the German Information Network of Departments of Dermatology (IVDK) collective (n = 2035)] were determined by the MOAHLFA (male, occupational dermatosis, atopic eczema, hand dermatitis, leg dermatitis, facial dermatitis, age ≥ 40 years) index. Statistically significant factors for periocular eczema are female sex, atopic skin diathesis and age ≥ 40 years. In both cohorts allergic contact dermatitis was the main cause of periorbital eczema (Erlangen 44·3%, IVDK 31·6%), followed by periorbital atopic dermatitis (Erlangen 25%, IVDK 14·1%), airborne dermatitis (Erlangen 10·2%, IVDK 1·9%), irritant contact dermatitis (Erlangen 9·1%, IVDK 7·6%), periorbital rosacea (Erlangen 4·5%, IVDK 2·2%), allergic conjunctivitis (Erlangen 2·3%, IVDK included in ‘others’) and psoriasis (Erlangen 2·3%, IVDK included in ‘others’). The most relevant allergens/allergen sources inducing periorbital eczema were consumers’ products (facial cream, eye shadow and ophthalmic therapeutics) (31%), fragrance mix (19%), balsam of Peru (10%), thiomersal (10%) and neomycin sulphate (8%); 12·5% of patients with allergic periocular dermatitis could be exclusively elucidated by testing patients’ own products. Conclusions Our data demonstrate the multiplicity of causes for periorbital eczematous disease manifestation, which requires patch testing of standard trays as well as consumers’ products to elucidate the relevant contact sensitization.     

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.     

Filaggrin null mutations increase the risk and persistence of hand eczema in subjects with atopic dermatitis: results from a general population study

Summary Background Hand eczema is prevalent in the general population. It remains unclear whether or not filaggrin gene (FLG) null mutations increase the overall risk of hand eczema or only increase the risk of hand eczema in subjects with atopic dermatitis. Objectives To investigate the association between FLG null mutations and hand eczema. Methods A random sample of 3335 adults from the general population in Denmark was patch tested, FLG genotyped for R501X and 2282del4 null mutations and questioned about hand eczema. Results Participants with combined presence of atopic dermatitis and FLG null mutation status had a significantly higher prevalence of hand eczema, an earlier onset of hand eczema and a higher persistence of hand eczema compared with subjects with normal FLG status and absence of atopic dermatitis. Logistic regression analyses revealed positive associations between hand eczema within the past 12 months and FLG null mutation status in participants with a history of atopic dermatitis [odds ratio (OR) 2·98; 95% confidence interval (CI) 1·27–7·01], but not in subjects without atopic dermatitis (OR 0·82; 95% CI 0·41–1·67). Conclusions FLG null mutations were significantly associated with hand eczema (< 12 months) in subjects with atopic dermatitis. Combined atopic dermatitis and filaggrin null mutation status was strongly associated with early onset of hand eczema and hand eczema persistence.     

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.     

Ichthyosis vulgaris: the filaggrin mutation disease

Ichthyosis vulgaris is caused by loss‐of‐function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker‐skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin‐deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.     

Impact of atopic dermatitis and loss‐of‐function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis

Background Atopic dermatitis (AD) and loss‐of‐function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD or whether the risk is mediated by AD. Objectives To investigate the relative contribution and interaction of FLG mutations and AD in German patients with occupational ICD and controls (vocational school apprentices). Methods A total of 634 patients and 393 controls were genotyped for R501X, 2282del4, R2447X and S3247X. Current or past flexural eczema was used as an indicator of AD. Results FLG mutations were found in 15·9% of the patients with ICD and 8·3% of the controls, with a crude odds ratio (OR) of 2·09 [95% confidence interval (CI) 1·33–3·28] for the combined genotype. The adjusted OR for FLG mutations, corrected for AD, was 1·62 (95% CI 1·01–2·58). Subjects with AD were at approximately three times higher risk of developing ICD than controls (OR 2·89; 95% CI 2·09–3·99). There was no evidence of an interaction between these two risk factors. Conclusions Our results indicate that both FLG mutations and AD increase the risk of ICD. Individuals with concurrent FLG mutations and AD are at the highest risk of developing ICD.     

The prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure

Background Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water‐soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers. Objectives To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. Patients and methods A retrospective analysis of patch test data was performed (n = 16 228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a χ² test. Logistic regression analyses were used to test for associations. Results The prevalence of chromium allergy decreased significantly from 3·6% in 1985 to 1% in 1995 (P_trend < 0·001) but increased to 3·3% in 2007 (P_trend < 0·001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12·7% in 1989–1994 to 3·0% (P < 0·01) in 1995–2007, whereas the frequency of relevant leather exposure increased significantly from 24·1% during 1989–1994 to 45·5% during 1995–2007 (P < 0·02). Conclusions Chromium allergy is currently increasing in Denmark due to leather exposure.     

The sweat of patients with atopic dermatitis contains specific IgE antibodies to inhalant allergens

We have investigated levels of total and specific against inhalant allergens in the sweat of 15 patients with atopic dermatitis, 10 patients with allergic rhinitis and high levels of specific IgE in the serum, and five patients with psoriasis without atopy as controls, by means of various commercial methods such as fluorescence immunoassay, nephetometry, chemiluminescence assay, enzyme immunoassay and the radioallergosorbent lest. Total IgE and specific IgE antibodies were detectable in the sweat of patients with atopic dermatitis as well as of patients with allergic rhinitis alone. These levels of total IgE in the sweat correlated with the severity of the skin disease (P < 0·05). By means of the Ciba Corning assay (P < 0·001), the fluorescence immunoassay (P < 0·05) and the nephelometry assay (P < 0·05), positive correlations were then established between the levels of total IgE in the serum and the sweat. Moreover, specific IgE antibodies to birch pollen and Dermatophagoides pteronyssinus were detectable in the sweat and correlated positively with these specific IgE levels in the serum (P < 0·05). Further, the specific IgE levels against these allergens in the sweat also correlated with the severity of dermatitis (P < 0·05). It is suggested that these specific IgE antibodies against certain inhalant allergens in the sweat of patients with atopic dermatitis may play a role in allergen trapping in the skin.     

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.     

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.     

Association between atopic dermatitis and obesity in adulthood

Background Obesity in early childhood is associated with increased risk for and severity of atopic dermatitis (AD). Objective  To determine whether obesity in adulthood is associated with risk of AD. Methods This was a retrospective case–control study of 2090 adults using questionnaire, height and weight, and skin‐prick testing between January 1994 and December 2003. Results  Obesity in adults was associated with increased AD [multinomial logistic regression: adjusted odds ratio (aOR) 1·43, 95% confidence interval (CI) 1·08–1·89; P = 0·01], but not nonatopic dermatitis (aOR 0·59, 95% CI 0·21–1·68; P = 0·32). Obesity was also associated with increased atopic asthma (aOR 1·98, 95% CI 1·47–2·66, P < 0·0001), but not associated with nonatopic asthma (P = 0·20), atopic or nonatopic rhinoconjunctivitis (P = 0·08 and 0·31, respectively), food allergies (P = 0·67 and 0·35, respectively) or atopy (P = 0·40). The association between obesity and AD remained significant even when controlling for history of asthma, rhinoconjunctivitis and food allergies (aOR 1·40, 95% CI 1·05–1·86; P = 0·02) or in subset analyses of subjects with AD alone (aOR 1·96, 95% CI 1·02–3·75; P = 0·04) and with comorbid asthma, rhinoconjunctivitis and/or food allergies (aOR 1·40, 95% CI 1·03–1·91; P = 0·03). Conclusion Obesity in adulthood is associated with AD. Further studies are warranted to determine if weight loss may prevent or mitigate AD in adults.     

Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations

Background  Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD. Objectives  To investigate further the spectrum of FLG‐null mutations in Chinese patients and to compare it with that in other populations. Methods  We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate‐to‐severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results  In total, 22 FLG‐null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher’s exact test; P = 5·3 × 10^?9; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher’s exact test; P = 9·0 × 10^?15; OR 5·8), keratosis pilaris (Fisher’s exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063). Conclusions  This study emphasizes the wider genetic landscape of FLG‐null mutations in Asia that is slowly emerging.     

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Background Narrowband ultraviolet B (NB‐UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. Objectives To examine whether NB‐UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB‐UVB on antimicrobial peptide and cytokine expression in the skin. Methods Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB‐UVB exposures on the whole body, given three times a week. Serum calcidiol (25‐hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real‐time quantitative polymerase chain reaction. Results At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L^?1). NB‐UVB treatment significantly increased (P < 0·001) serum calcidiol. The increase was 59·9 nmol L^?1 (95% confidence interval, CI 53·5–66·9) in psoriasis, 68·2 nmol L^?1 (95% CI 55·4–80·1) in AD and 90·7 nmol L^?1 (95% CI 63·8–123·4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0·001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human β‐defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB‐UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB‐UVB caused a marked but nonsignificant decrease of interleukin (IL)‐1β and IL‐17 in psoriasis lesions. Conclusions The present study shows that in addition to a significant improvement of psoriasis and AD, NB‐UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.     

Expression of CD30 on T helper cells in the inflammatory infiltrate of acute atopic dermatitis but not of allergic contact dermatitis

Abstract  The CD30 molecule has been proposed as a marker for a subset of CD4⁺CD45RO⁺ (memory) T cells with potent B cell helper activity producing IL-5 and IFN-γ and as a specific marker for Th2 cells. Recently, an association has been demonstrated between elevated serum levels of soluble CD30, which is shed by CD30⁺ cells in vitro and in vivo, and atopic dermatitis but not respiratory atopic disorders or allergic contact dermatitis. We studied the expression of CD30 in the inflammatory infiltrate of atopic dermatitis compared with that of allergic contact dermatitis, with special regard to skin disease activity (acute vs subacute/ chronic). Biopsies were obtained from 16 patients suffering from atopic dermatitis (acute n = 6, subacute/ chronic n = 10), from 7 patients with acute allergic contact dermatitis and from 5 positive patch-test reactions. Paraffin-embedded as well as snap-frozen material was stained with anti-CD30 and anti-CD45RO mAbs according to standard procedures. Double-staining procedures for CD30CD3, CD30CD4, CD30CD45RO and CD30CD68 were also performed. Abundant CD45RO⁺ cells were detected both in atopic dermatitis and in allergic contact dermatitis lesions. We found scattered CD30⁺ cells in only one of six formalin-fixed paraffin-embedded acute atopic dermatitis biopsies, but in all of the respective snap-frozen specimens, possibly because CD30 expression on atopic dermatitis infiltrating cells is weak and sensitive to formalin fixation and paraffin embedding. CD30CD3 and CD30CD4 double staining identified CD30⁺ cells to be helper T lymphocytes. No significant CD30 expression (either in paraffin-embedded or in frozen material) could be found in subacute/chronic atopic dermatitis lesions or in any of the specimens of allergic contact dermatitis. The results suggest a specific regulatory function of CD30⁺ T cells in acute atopic dermatitis. With respect to the view that CD30 is a marker for Th2 cells, our observations confirm previous findings that Th2 cells predominate in the infiltrate particularly of acute atopic dermatitis. CD30 expression in acute atopic dermatitis but not in acute allergic contact dermatitis might be helpful in the histological differentiation of these disorders and in the further characterization of atopy patch testing. Received: 1 April 1998 / Received after revision: 28 May 1998 / Accepted: 3 July 1998     

Nickel skin levels in different occupations and an estimate of the threshold for reacting to a single open application of nickel in nickel-allergic subjects

Background Nickel is a frequent allergen throughout the world. However, the extent to which nickel is relevant as an occupational contact allergen as opposed to being simply a reflection of jewellery exposure has been unclear. Some thresholds for cutaneous nickel exposure to induce a dermatitis reaction in nickel‐allergic individuals have been defined. Over recent years it has become possible to measure accurately the quantity of nickel on the skin of individuals in a number of occupations. Objectives To measure the quantities of nickel on the skin of the fingers in workers employed in occupations for which nickel has been suspected as a contact allergen. To define the threshold for a dermatitis reaction after the single application of a quantity of nickel to the skin of nickel‐allergic individuals when read at 2 days. Methods We employed the ‘finger immersion’ technique for sample collection and induction coupled plasma mass spectrometry for the nickel measurement. Nickel platers, cashiers, sales assistants, caterers, healthcare assistants, office workers, dental nurses and hairdressers were studied (five in each group except for seven cashiers). A correction was made for the fact that the finger immersion method underestimates the amount of nickel on the fingertip. The threshold for reactivity to a single application of nickel was studied by the application of various concentrations of nickel (μg cm^?2) [0·05 (two subjects), 0·5 (two subjects), 2·5 (three subjects), 5·0 (21 subjects), 15 (19 subjects), 30 (19 subjects) and 45 (18 subjects)] in 21 subjects overall using Finn chambers on forearm skin. The reading was made at 2 days and reactions were graded using the International Contact Dermatitis Research Group classification. Results Nickel levels on the fingers of platers, cashiers, sales assistants, caterers, and even office staff, were at or above the 0·035 μg cm^?2 level at which 22% of nickel‐allergic subjects will react (after applying a correction). The single open application of nickel study demonstrated a dose–response relationship, with no subjects reacting to ≤ 2·5 μg cm^?2, but increasing numbers reacting at the higher concentrations as follows: six of 21 (28%) at 5·0 μg cm^?2, six of 19 (31%) at 15 μg cm^?2, seven of 19 (37%) at 30 μg cm^?2 and 11 of 18 (61%) at 45 μg cm^?2. Conclusions This study confirms that nickel levels on the skin in coin handling occupations and some others are sufficient to induce an allergic contact dermatitis in some nickel‐allergic subjects. A single application of 5 μg cm^?2 when read at 2 days induced a dermatitis reaction in six of 21 nickel‐allergic subjects.     

Serum chemerin is increased in patients with chronic plaque psoriasis and normalizes following treatment with infliximab

Background Chronic plaque psoriasis is associated with obesity, which is a metabolic and inflammatory disorder. Adipokines are involved in the pathogenesis of psoriasis and they are biomarkers of obesity‐related inflammation. Objectives To measure serum adipokines in patients with chronic plaque psoriasis treated with infliximab. Methods Serum levels of chemerin, resistin, visfatin, C‐reactive protein (CRP), lipids, glycaemia and liver enzymes were measured in 40 patients with psoriasis and 40 controls matched by age, sex and body mass index (BMI). Adipokines were measured at baseline and after 2–12 months of treatment with infliximab 5 mg kg^?1. Results At baseline, levels of chemerin (195·9 ± 48·5 vs. 145·6 ± 27·1 ng mL^?1), resistin (2·03 ± 0·9 vs. 1·4 ± 0·5 ng mL^?1) and CRP (5·5 ± 7·3 vs. 1·9 ± 4·4 mg L^?1) were higher (P < 0·01) in patients with psoriasis compared with controls. Psoriasis was associated with elevated chemerin level independently of age, sex, BMI and levels of cholesterol and triglycerides. Chemerin was linearly correlated to CRP (r = 0·4, P = 0·01) and resistin (r = 0·3, P = 0·01). Chemerin levels were higher in patients affected by psoriatic arthritis than in patients with psoriasis without arthritis (195·5 ± 49·1 vs. 158·1 ± 37·5 ng mL^?1, P = 0·01). After 2 months of infliximab treatment a significant reduction of chemerin, resistin and CRP levels was observed. Conclusions Patients with psoriasis have higher blood levels of adipokines, which normalize during therapy with infliximab. Whether this reduction is a direct effect of infliximab or secondary to a reduction of inflammation should be further investigated.     

Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy

We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydro-xylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period. Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1·6g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298±849 ng/ml (mean+SD) at baseline to 3006±1131 ng/ml at week 3 of cimetidine (P<0·01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446±954 ng/ml when cimetidine was stopped (P<0·02). The methaemoglobin fell from 5·5·2·2% (mean±SD) at baseline to 3·9±1·1% at week 3 (P<0·01). and remained low until week 12, when there was a return to baseline values (P<0·01). The haemoglobin did not change from the baseline of 12·7·0·3 g/dl (mean±SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P<0·05), but this was not associated with any deterioration in control of the skin disorders. Hence, long-term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months. Cimetidine thus improves the therapeutic/toxic ratio of dapsone. Such a therapeutic strategy may be appropriate for patients who require high-dose dapsone, or those who are particularly susceptible to dapsone-induced haemotoxicity.