Associations of acanthosis nigricans with metabolic abnormalities in polycystic ovary syndrome women with normal body mass index

Acanthosis nigricans (AN) usually correlates to insulin resistance (IR) or obesity in obese populations, but adequate studies on the significance of AN in people with normal body mass index (BMI) have not been performed and discussed. Three hundred and thirty‐nine polycystic ovary syndrome (PCOS) patients with normal BMI (<23 kg/m²) were recruited. The anthropometric and biochemical parameters of these patients were measured. In these patients with normal BMI, 33 (9.7%) women had AN, and six (1.77%) women were diagnosed with metabolic syndrome. Most of the anthropometric and biochemical variables associated with metabolic status were more unfavorable in the AN‐positive group compared with the AN‐negative groups. The prevalence of central obesity, IR and reduced high‐density lipoprotein cholesterol (HDL‐C) level were also significantly higher in the AN‐positive group (P < 0.05). In multiple regression analysis, presence of AN was still significantly associated with IR (odds ratio [OR] = 2.952, 95% confidence intervals [CI] = 1.367–6.376] and reduced HDL‐C level (OR = 2.668, 95% CI = 1.160–6.135) after adjustments for age and BMI. Sensitivity, specificity, and positive and negative predictive values for AN to detect IR were 18.6%, 92.6%, 39.4% and 81.4%, respectively. In conclusion, presence of AN correlated with IR and reduced HDL‐C level in PCOS women with normal BMI. AN status had high specificity to detect IR, but lack of sensitivity.     

Assessment of serum leptin,insulin resistance and metabolic syndrome in patients with skin tags

Background Skin tags are common cutaneous lesions with an indefinite aetiology. Objectives To assess serum leptin, insulin resistance and metabolic syndrome in different body mass index (BMI) patients with skin tags. Methods Three equally distributed groups of patients with multiple skin tags: 30 normal BMI, 30 overweight and 30 obese were included. Controls were age‐, gender‐ and BMI‐matched healthy subjects. Serum leptin, insulin resistance based on homeostasis model assessment of insulin resistance (HOMA‐IR) and metabolic syndrome were assessed in all groups. Results Number and extent of skin tags increase with the increase in BMI. Highest leptin levels were found in obese patients, with significant differences when compared to normal BMI and overweight patients. Similar findings existed in controls. Significantly higher leptin levels were found in obese patients compared to obese controls. HOMA‐IR was significantly higher in all groups of patients compared to BMI‐counterpart controls. Seventy‐one per cent of patients fulfilled criteria of metabolic syndrome. Number of skin tags, leptin and HOMA‐IR were significantly higher in patients with metabolic syndrome compared to patients without the syndrome. Positive correlations were found between serum leptin and HOMA‐IR in obese patients and obese controls. Positive correlations were also found between number of skin tags and waist circumference in all groups of patients. Conclusions Serum leptin displays an association with obesity and insulin resistance. Assessment of HOMA‐IR in patients with skin tags may serve as a useful approach for diagnosis of insulin resistance. Waist circumference is the only criteria of metabolic syndrome that correlates with number of skin tags.     

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll‐like receptor (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more prominent in the obese mice than in the control mice. When compared to imiquimod‐treated control mice, imiquimod‐treated obese mice expressed higher levels of psoriasis mediators, interleukin‐17A (IL‐17A) and IL‐22 in the skin. Food intake restriction partially abrogated enhanced ear swelling and cytokine overproduction in obese mice. Furthermore, the obesity environment and imiquimod treatment synergistically induced an IL‐17A downstream molecule, regenerating islet‐derived 3γ (Reg3γ), which is a critical molecule for psoriatic epidermal hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous adipocytes, increased the expression of REG3A (a human homologue of mouse Reg3γ) in both the HaCaT keratinocyte cell line and normal human keratinocytes. Taken together, these results strongly suggest that obesity exacerbates psoriasiform dermatitis in mice by upregulating IL‐17A, IL‐22 and Reg3γ.     

Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4+ CD25highFoxP3+ T‐regs cells

Not only macrophages, T‐helper (Th)1 and Th2, but also CD4⁺ CD25^highFoxP3⁺ regulatory T cells (T‐regs) are involved in immune response to Mycobacterium leprae. We aimed to evaluate serum interleukin (IL)‐1β and IL‐12p70 (macrophage cytokines), interferon‐γ (IFN‐γ) (Th1 cytokine), IL‐4 (Th2 cytokine) and circulating CD4⁺ CD25^highFoxP3⁺ T‐regs, in untreated leprosy patients. Forty three patients and 40 controls were assessed for the mentioned cytokines using ELISA. Patients were assessed for circulating T‐regs using flow cytometry. Patients were subgrouped into tuberculoid (TT), pure neural leprosy (PNL), borderline cases, lepromatous (LL), type 1 reactional leprosy (RL1) and erythema nodosum leprosum (ENL). Serum IL‐12p70, IFN‐γ and IL‐4 were significantly higher in patients versus controls (P < 0.05). Serum IL‐4 was highest in LL and lowest in RL1 (P = 0.003). Serum IL‐1β levels was significantly higher in multibacillary versus paucibacillary patients (P = 0.006). Significantly higher T‐regs levels was detected in TT, RL1 and PNL, while the lowest levels in ENL(P < 0.001), with significant differences versus controls (P < 0.05). FoxP3 expression% was significantly lower in PNL than other patients and controls (P < 0.05). T‐regs/T‐effs was lowest in ENL(P < 0.05). IFN‐γ correlated positively with T‐regs but negatively with IL‐1β (P = 0.041&0.046 respectively), which correlated positively with T‐effs%( P = 0.05). IL‐4 correlated positively with T‐regs FoxP3 expression% (P = 0.009). We concluded that: Circulating T‐regs were increased in TT, RL1 and PNL patients, known of relatively high cell‐mediated immunity. This finding was supported by low FoxP3 expression (in PNL) and correlation between T‐regs count and IFN‐γ level. Overproduction of IL‐4 in LL may infer liability to develop ENL, with disease progression and immune hyperactivation, marked by deficient T‐regs and increased T‐regs FoxP3 expression%. IL‐1β probably has a pro‐inflammatory role in multibacillary patients as correlated with T‐effs%.     

Dermatoses in overweight and obese children and their relationship with insulin and skin color

Background/Aim

The aim of the present study was to investigate the prevalence of obesity-related dermatoses in obese children, and the association between these dermatoses and insulin resistance as well as skin color.

Methods

Obese, overweight, and normal weight children according to body mass index who were followed up and treated in the outpatient clinics were included in the study. Dermatological examinations of the participants were performed, and fasting insulin and glucose levels were checked.

Results

The obese and overweight children were evaluated as the patient group (70 girls, 41 boys, mean age: 12.37 ± 3.14 years). One hundred one healthy children with normal weight were determined as the control group (59 girls, 42 boys, mean age: 12.15 ± 2.43). The first five common dermatoses in the patient group when compared with the control group were keratosis pilaris (KP), striae distensae, hyperhidrosis, acanthosis nigricans (AN), and plantar hyperkeratosis. The first five dermatoses which were positively correlated with formation and insulin resistance were KP, striae distensae, AN, hyperhidrosis, and plantar hyperkeratosis. According to the Fitzpatrick skin scale, we found that the darker the skin color, the higher the probability of AN and KP (OR, 0.298; 95% CI, 0.106–0.834, p = 0.021; OR, 0.306; 95% CI, 0.117–0.796, p = 0.015, respectively).

Conclusion

Some dermatoses associated with obesity and insulin resistance were not found in obese children, or there was no significant association. These results indicate that many skin morbidities may be prevented by preventing and treating obesity and insulin resistance in the early period.     

Concomitant confluent and reticulated papillomatosis and acanthosis nigricans in an obese girl with insulin resistance successfully treated with oral minocycline: Case report and published work review

Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity‐associated AN in a 12‐year‐old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity‐associated AN are discussed. In addition, reports of concomitant CRP and obesity‐associated AN are reviewed. CRP and obesity‐associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity‐associated AN. Together with the observation that skin lesions of CRP and obesity‐associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.     

The Akkermansia muciniphila is a gut microbiota signature in psoriasis

Psoriasis is an immune‐mediated chronic inflammatory skin disease. Although its pathogenesis is not fully understood, Th17 cells and the cytokines they produce, such as IL‐17, IL‐22 and IL‐23, play critical roles in the pathogenesis of psoriasis. Evidence has demonstrated that psoriasis has some common features, including immune responses (due to Th17 cells) and inflammatory cytokine profiles, with systematic diseases including inflammatory bowel diseases (IBDs) and obesity. Recently, studies have demonstrated that the gut microbiota plays a crucial role in host homoeostasis and immune response, particular in Th17 cells, but the role of the gut microbiota in psoriasis remains unclear. To study the relationship between gut microbiota and psoriasis, we analysed microbiota profiles in psoriasis using a 16S rDNA sequencing platform, and we found that the abundance of Akkermansia muciniphila was significantly reduced in patients with psoriasis. A. muciniphila is believed to have an important function in the pathogenesis of IBD and obesity; therefore, A. muciniphila, which is an indicator of health status, may be a key node for psoriasis as well as IBD and obesity. Taken together, our study identified that gut microbiota signature and function are significantly altered in the gut of patients with psoriasis, which provides a novel angle to understanding the pathogenesis of psoriasis.     

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index,severity and therapy

Background Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels. Objectives To understand the role/relationship of adipokines, as well as CRP, in a Portuguese psoriatic population, by assessing the relationship of their levels with psoriasis severity, defined by Psoriasis Area and Severity Index (PASI), with obesity, defined by body mass index (BMI), and psoriasis therapy. Methods A cross‐sectional (n = 66) and longitudinal study (before and after 12 weeks of therapy; n = 44) was performed; 10 patients started topical treatment, 17 narrow‐band ultraviolet B (NBUVB) and 17 psolaren associated with UVA (PUVA). Results Patients presented significantly higher BMI, leptin, resistin, TNF‐α, IL‐6 and CRP and significantly lower adiponectin values. CRP and IL‐6 correlated with PASI. Adiponectin and leptin were more altered in patients with higher BMI. Concerning severity, CRP, resistin and adiponectin were more altered in the severer forms. After treatment, a significant reduction in PASI, CRP, resistin, TNF‐α and IL‐6, and a significant rise in adiponectin were observed. Nonetheless, CRP and adiponectin remained different from those of control. Concerning therapies, topical therapy was not associated with any significant change, except for TNF‐α. After NBUVB, a significant reduction was observed in TNF‐α and in CRP. For PUVA, we observed a significant reduction in TNF‐α, IL‐6 and CRP, and a significant increase in adiponectin. Conclusion In psoriatic patients, increased overweight/obesity was associated with raised leptin levels and decreased adiponectin levels. Leptin may contribute to enhance the inflammatory process in overweight/obese psoriatic patients. Resistin, IL‐6, CRP and adiponectin levels appear to be dependent on psoriasis severity. CRP, together with IL‐6, appears to be a useful marker of psoriasis severity. Both NBUVB and PUVA were effective; however, PUVA results seem to be more successful. Nonetheless, after NBUVB and PUVA, a low‐grade inflammation still persists.     

Interleukin‐10 secretion from CD14+ peripheral blood mononuclear cells is downregulated in patients with acne vulgaris

Background Acne is a common chronic inflammatory dermatosis of the pilosebaceous unit. It is characterized by seborrhoea, comedone formation and an inflammatory response consistent with defective cellular immunity to Propionibacterium acnes. Objectives The objective of this study was to investigate the immune reactivity of patients with acne compared with healthy controls by examining the response of peripheral blood mononuclear cells (PBMCs) to stimulation with P. acnes. Particular focus was placed upon measuring the production of interleukin (IL)‐10, which has an established immunoregulatory role. Patients and methods Venous blood was collected from 47 patients with acne and 40 age‐ and sex‐matched healthy controls with no prior history of acne. PBMCs were cultured and their cytokine response to P. acnes investigated. Results Proinflammatory IL‐8 and tumour necrosis factor (TNF)‐α secretion from PBMCs was higher in patients with acne when stimulated with P. acnes. In contrast, a statistically significant reduction in PBMC secretion of anti‐inflammatory IL‐10 in patients with acne was identified. The impaired production of IL‐10 by PBMCs from patients with acne was confined to CD14+ cells presumed to be monocytes. The ability of CD14 cells from patients with acne to phagocytose P. acnes bacteria was also observed to be defective but the addition of exogenous IL‐10 to PBMC cultures restored phagocytic activity. Conclusions These data suggest that patients with acne have a proinflammatory cytokine milieu and crucially are unable to contain early inflammatory changes due to a specific defect in immunosurveillance, namely low monocyte IL‐10 production. Our observations raise the possibility that acne therapeutics might profitably target IL‐10 both as a regulator of proinflammatory cytokines and in augmenting the CD14+ cell phagocytic response.     

Reduction of inflammatory slan (6‐sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept

Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro‐inflammatory TNF‐α, IL‐23‐ and IL‐12‐producing DCs in human blood and as prominent inflammatory dermal TNF‐α secreting and CD11c‐positive DC subset in psoriasis. Here, we ask for the effects of TNF‐α‐inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24 weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase‐3‐expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA‐DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL‐1β, IL‐6, IL‐23 and IL‐12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF‐α is an autocrine stimulus for maturation and pro‐inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF‐α and IL‐23p19. However, successful treatment did not down‐regulated the percentage of dermal slanDCs that stained positive for TNF‐α and IL‐23p19 indicating that remaining slanDCs kept their pro‐inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.     

Effects of isotretinoin on glucose metabolism in patients with acne: A systematic review and meta‐analysis

Previous studies reporting the influence of isotretinoin treatment on glucose metabolism have produced conflicting results. We therefore aimed to examine the effects of isotretinoin treatment on changes in insulin resistance and serum levels of adiponectin in patients with acne. A systematic review and meta‐analysis of the literature published from the inception of isotretinoin to March 31, 2019 were conducted. In the absence of controlled trials, open‐label studies on acne patients receiving isotretinoin treatment were included. Twelve studies met the inclusion criteria. The outcomes included changes in the homeostasis model assessment for insulin resistance (HOMA‐IR) values and serum levels of adiponectin after isotretinoin treatment. Pooled analysis showed that HOMA‐IR values did not change significantly after isotretinoin treatment (standardized mean difference [SMD] = 0.183; 95 % confidence interval [CI] = ?0.004–0.371; I² = 38.3), whereas the level of adiponectin significantly increased (SMD = 0.512; 95 % CI = 0.327–0.698; I² = 10.7). Our study concluded that isotretinoin treatment for patients with acne resulted in an increased serum level of adiponectin but did not have a substantial impact on the status of insulin resistance.     

Longitudinal observational study of hidradenitis suppurativa: impact of surgical intervention with adjunctive biologic therapy

Background

Hidradenitis supppurativa (HS) is a chronic inflammatory disease of the apocrine sweat glands affecting 1–4% of the population. While surgical excision is a mainstay of therapy, lesions often recur. Biologic therapies, including tumor necrosis factor‐α and IL‐12/23 inhibitors, are effective for mild to moderate HS. However, longitudinal studies investigating biologic therapy in conjunction with surgery are limited. The purpose of this analysis was to investigate impact of surgery and biologic therapy on HS disease activity.

Methods

Data from 68 HS patients were analyzed. Outcome measures included hidradenitis suppurativa Sartorius Score (HSS), active nodule (AN) count, Hurley stage, and probability of achieving 75% reduction in active nodule count (AN75).

Results

Mean age was 40 ± 14 years; 66% were female and 72% were African American. Mean disease duration was 10 years, and Hurley stage III disease was seen in 63% of patients. Patients who received biologics had a larger drop in HSS and AN count than those who never received biologics (P = 0.002). Biologic treatment was associated with average reduction in 22 (15–29) HSS points (P < 0.0001). The effect of biologics was greater in patients who also underwent surgery (P = 0.013). Timing of biologics relative to surgery did not impact efficacy. Patients who received HS surgery with biologic therapy were most likely to achieve the AN75 (P = 0.017).

Conclusions

In this diverse cohort of patients with severe HS, biologic therapy was associated with a more rapid decline in disease activity, with the greatest effect in patients who also underwent HS surgery.     

Clear differences in adiponectin level and glutathione redox status revealed in obese and normal-weight patients with psoriasis

Background Several studies have shown increased prevalence of obesity in patients with psoriasis. Objectives To characterize both inflammatory‐ and oxidative stress‐related differences between obese patients with psoriasis (OPP) and normal‐weight patients with psoriasis (NWPP). Methods The plasma concentrations of adiponectin and interleukin (IL)‐6 were analysed by quantitative sandwich enzyme immunoassay technique in 10 patients with a body mass index (BMI) < 25 and 12 patients with a BMI > 30. Total glutathione and oxidized glutathione levels were measured spectrophotometrically. Results Plasma concentration of adiponectin in NWPP was more than twice the level in healthy normal‐weight controls (P < 0·001), while such an elevation did not occur in OPP. OPP were characterized by a significantly increased IL‐6 level, which correlated negatively with the adiponectin level (r = ?0·85, P < 0·001). The glutathione redox status, which was also inversely correlated with the adiponectin level (r = ?0·63, P < 0·05), was associated with significantly increased oxidative stress in the OPP compared with the NWPP or controls. Conclusions Obesity in patients with psoriasis is associated with both decreased plasma levels of protective adiponectin compared with NWPP, and enhanced systemic inflammation and oxidative stress. These findings are in concordance with high prevalence of diseases related to lower adiponectin levels among psoriasis patients.     

Allergic contact dermatitis beyond IL‐1β role of additional family members

Contact dermatitis is one of the most frequent pathological manifestations of the skin and plays a central role in clinical dermatology. The IL‐1 family consists a large group of cytokines, which currently contains 11 members with different pro‐ and anti‐inflammatory properties. Among the more pro‐inflammatory‐acting cytokines from the IL‐1 family, IL‐1β, IL‐18, IL‐33 and IL‐36 have been shown to be upregulated in different inflammatory mouse experimental models or skin diseases. The article by Mattii et al. represents a thorough analysis of the expression of IL‐1 family members including IL‐33 in skin samples from patients with allergic contact dermatitis. Although a lot of research is performed in this area, data from human samples are rather scarce. Therefore, Mattii et al. support the development of novel therapeutic concepts, which might include the use of antagonistic molecules targeting the IL‐1 family network.     

Specific interleukin-1 gene polymorphisms in Turkish patients with Behçet's disease

Abstract: Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. The pro‐inflammatory cytokine interleukin‐1 (IL‐1) has been implicated in the pathogenesis of BD. Our aim was to determine a possible association of specific polymorphisms of IL‐1α, IL‐1β, and IL‐1 receptor antagonist genes with susceptibility for BD. We genotyped 72 patients with BD and 163 healthy controls for IL‐1α?889, IL‐1β?511, and +3953 (nt5887) single‐nucleotide polymorphisms besides IL‐1 receptor antagonist variable number of tandem repeat polymorphism (for five different alleles). Comparison of the IL‐1β+3953 T allele and TT genotype frequencies showed a significant difference between patients with BD and controls (54.2 vs. 40.5%, OR = 1.74, P = 0.024, and 40.3 vs. 19.6%, OR = 2.76, P = 0.009, respectively). However, no difference was observed in the genotype or allele frequencies of IL‐1α?889, IL‐1β?511, and IL‐1 receptor antagonist between the patients with BD and the controls. Our results indicate that susceptibility to BD is increased in individuals carrying the IL‐1β+3953 T allele and TT genotype.     

Levels of Interleukin‐18 and Endothelin‐1 in Children with Henoch‐Schönlein Purpura: A Study from Northern India

Henoch‐Schönlein purpura (HSP) is an acute systemic vasculitis with unknown etiology, although several studies have found HSP to be related to cytokines such as tumor necrosis factor α, interleukin (IL)‐1, and adhesion molecules. In the present study we determined the levels of cytokines such as IL‐18 and endothelin‐1 (ET‐1) in children with HSP. Subjects were divided into three groups (group 1, 20 subjects with HSP; group 2, 10 subjects belonging to group 1 during their follow‐up 4 to 6 months later; and group 3, 16 controls who were healthy siblings of the subjects). IL‐18 and ET‐1 levels were determined using enzyme immunoassay and expressed as mean ± standard deviation. We observed higher IL‐18 levels in children with HSP (767.6 ± 145.1 pg/mL) than in controls (614.6 ± 66.54 pg/mL, p > 0.05), but IL‐18 levels were found to be significantly lower in subjects with HSP in remission (502.7 ± 60.81 pg/mL) than in those who were in an active phase (1,050 ± 244.5 pg/mL, p < 0.05, n = 10). ET‐1 levels were found to be significantly higher in subjects with HSP (1.93 ± 0.19 pg/mL) than in controls (1.10 ± 0.13 pg/mL, p < 0.05), although no significant difference was observed in ET‐1 levels between subjects in group 1 (1.88 ± 0.30 pg/mL) and group 2 (1.91 ± 0.120, p > 0.05, n = 10). A positive correlation was observed between IL‐18 and ET‐1 levels in subjects with HSP (correlation coefficient [r] = 0.5254, p < 0.01). These results suggest that levels of IL‐18 and ET‐1 are worth monitoring during the clinical course of the disease, but caution must be exercised in extrapolating data based on small study samples.     

Increased serum HMGB1 levels in patients with Henoch–Schönlein purpura

High‐mobility group box‐1 (HMGB1) has been implicated as a pro‐inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch–Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro‐inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC‐1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme‐linked immunosorbent assay (ELISA). HMEC‐1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF‐α and IL‐6 release in cultured supernatant. Furthermore, by real‐time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC‐1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB‐α (IκBα) and the nuclear translocation of nuclear factor‐κB (NF‐κB) p65 in HMEC‐1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF‐α and IL‐6 production and may play a crucial role in the pathogenesis of HSP.     

Study of pro‐ and anti‐inflammatory cytokine profile in the patients with parthenium dermatitis

Background: Parthenium dermatitis is a common airborne allergic contact dermatitis induced by exposures to the weed Parthenium hysterophorus. The disease manifests as itchy erythematous papules, papulovesicular and plaque lesions on exposed areas of the body. Objectives: The aim of this study was to show the alterations in pro/anti‐inflammatory cytokines in parthenium dermatitis. Methods: The study included 50 patients with parthenium dermatitis confirmed by patch testing using aqueous extracts of P. hysterophorus and 50 age‐matched healthy controls. The levels of pro‐inflammatory [tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6, IL‐8, and IL‐17] and anti‐inflammatory (IL‐4 and IL‐10) cytokines were estimated by commercially available high sensitivity enzyme‐linked immunosorbent assay (ELISA) kits. Results: All the dermatitis patients showed significantly (P < 0.001) elevated levels of TNF‐α, IL‐6, IL‐8, and IL‐17 levels as compared to healthy controls. In contrast, the anti‐inflammatory cytokine IL‐4 showed an insignificant decrease (P < 0.217) and a decrease in level of IL‐10 was statistically significant (0.001) compared with controls. Conclusions: The present study suggests the involvement of pro‐inflammatory cytokines in the pathogenesis of parthenium dermatitis. A decrease in levels of anti‐inflammatory cytokines was demonstrated, which could not downregulate pro‐inflammatory cytokines in parthenium dermatitis.     

Markers of systemic inflammation in psoriasis: a systematic review and meta‐analysis

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)‐1β, IL‐6, IL‐10, C‐reactive protein (CRP), intracellular adhesion molecule (ICAM)‐1, E‐selectin and tumour necrosis factor (TNF)‐α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random‐effects model. Seventy‐eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL‐6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF‐α (d = 1·32, 95% CI 0·86–1·79), E‐selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM‐1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL‐1β and IL‐10 was not significant. Age had a significant effect on the SMD for IL‐6 and TNF‐α. For IL‐6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.