Plasma concentration of selected neuropeptides in patients suffering from psoriasis

The aim of this study was to evaluate plasma levels of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) during psoriasis course. METHODS: Seventy-three patients with psoriasis and 32 healthy volunteers were included. Detailed demographic and disease anamnesis was obtained from every patient. The disease severity was assessed using the Psoriasis Area and Severity Index score. Plasma levels of SP, CGRP, VIP and NPY were measured radioimmunologically. RESULTS: Plasma levels of SP and NPY did not significantly differ between patients with psoriasis and controls (median SP: 52.8 and 57.9 pg/ml, respectively; P = 0.32; median NPY: 8.5 and 8.2 pg/ml, respectively; P = 0.67). CGRP plasma concentration was significantly elevated in psoriatic individuals both before (median 43.1 pg/ml) and after treatment (median 45.4 pg/ml), in comparison with healthy donors (median 13.5 pg/ml; P < 0.01 and P = 0.03, respectively). Treatment did not significantly influence plasma CGRP levels (P = 0.3). Median VIP plasma concentration in psoriatics before treatment was significantly higher compared with healthy controls (medians 66.9 and 60.1 pg/ml, respectively; P = 0.04), but the therapy resulted in significant decrease in VIP plasma level (median 19.0 pg/ml; P < 0.001). In psoriatic patients significant correlations were noted between NPY and VIP (R = 0.34; P < 0.01), and VIP and CGRP plasma levels, both before (R = 0.28; P = 0.03) and after the treatment (R = 0.44; P < 0.01). CONCLUSIONS: Based on our results and previous literature data it could be suggested that neuropeptides may be involved in the development of psoriatic lesions.     

Neuronal changes in psoriasis exacerbation

Background The nervous system contributes to inflammatory skin diseases.
Objective The aim of this investigation was to study the neuronal contribution to psoriasis at the remission and exacerbation phases.
Methods We examined the expression of the neuronal markers protein gene product 9.5 (PGP 9.5), growth-associated protein-43 (GAP-43) and substance P, in addition to its receptor (R), neurokinin-1R (NK-1R) in psoriatic skin from seven female patients at remission and exacerbation, using immunohistochemistry.
Results The number of epidermal PGP 9.5 immunoreactive nerve fibres in the involved skin during exacerbation was decreased ( P  < 0.01) compared to involved skin at remission and non-involved skin at the exacerbation phase. GAP-43-positive nerve fibres were decreased ( P  < 0.05) in the involved skin in contrast to non-involved skin, during exacerbation. Substance P expression was seen on both immunoreactive nerve fibres and cells with a down-regulation ( P  < 0.01) in the number of positive nerve fibres in the involved skin compared to non-involved skin, at the exacerbation phase. The number of substance P-positive cells was slightly lower in the involved skin at exacerbation than at remission. The number of NK-1R immunoreactive cells was increased ( P  < 0.01) in the involved skin in contrast to non-involved skin, at the exacerbation phase.
Conclusion Our findings suggest a crosstalk between the nervous system and inflammation during psoriasis exacerbation in the form of an altered expression of nerve fibres, substance P and its NK-1R.     

Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis

Background  Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems.
Objectives  To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-γ production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls.
Methods  Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-γ production and HLA-DR expression were measured in both CLA+ and CLA− T-cell subsets by flow cytometry.
Results  CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD ( P  <   0·05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls ( P  <   0·05). Memory T cells incubated with CGRP also showed an increase in IL-13 ( P  <   0·05) and HLA-DR ( P  <   0·05) in CLA+ T cells from patients with AD compared with controls, but not in CLA− T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-γ ratio was increased in patients with AD after cells were cultured with CGRP ( P  <   0·05).
Conclusions  Our results suggest an immunomodulatory role of CGRP towards a Th2 pattern in CLA+ T cells, which may contribute to exacerbating clinical symptoms in patients with AD.     

特应性皮炎患者血浆中P物质的测定及其临床意义

目的 探讨特应性皮炎患者血清中P物质水平及其临床意义.方法 用放射免疫法测定35例特应性皮炎患者血浆中P物质浓度,观察P物质与疾病严重程度积分及嗜酸粒细胞数的关系.结果 特应性皮炎患者血浆中P物质浓度明显高于正常人对照P<0.01),且疾病的EASI评分和Rajka严重度积分与P物质浓度呈显著正相关,r分别为0.95和0.86,P均<0.01.特应性皮炎患者外周血嗜酸粒细胞数明显高于正常人对照(P<0.01),并且与疾病的严重度呈正相关(与EASI评分r=0.42,P=0.011,与Rajka严重度积分r=0.42,P=0.013):特应性皮炎患者血浆中P物质浓度与外周血嗜酸粒细胞数呈正相关(r=0.43,P=0.009).结论 P物质对判断特应性皮炎活动性可能有一定价值;P物质可能与嗜酸粒细胞共同参与特应性皮炎发病.     

Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P

BACKGROUND: Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. The pathophysiology of pruritus is complex and various neuropeptides may be involved. OBJECTIVE: To evaluate whether or not brain-derived neurotrophic factor (BDNF) and substance P are associated with disease severity, quality of life and nocturnal scratching in AD. METHODS: Patients with AD aged under 18 years were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, and quality of life with the Children's Dermatology Life Quality Index (CDLQI). Concentrations of plasma BDNF, substance P, AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK), thymus and activation regulated chemokine (TARC)], serum total IgE and eosinophil counts were measured in these patients. All children were instructed to wear the DigiTrac monitor on their dominant wrist while sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning. RESULTS: Twenty-eight children with AD [mean (SD) age 11.1 (3.3) years] were recruited. The mean (SD) SCORAD was 48.1 (21.5) and CDLQI was 8.7 (5.4) in the patients with AD. Their mean (SD) plasma concentrations of BDNF, substance P, CTACK and TARC were 1798 (935), 94 (42), 1424 (719) and 824 (1000) pg mL(-1), respectively. BDNF was significantly correlated with SCORAD (r = 0.478, P = 0.010) and CDLQI (r = 0.522, P = 0.004), whereas substance P showed significant correlation only with CDLQI (r = 0.441, P = 0.019). BDNF and substance P were also significantly correlated with the average (r = 0.905, P < 0.001 and r = 0.925, P < 0.001) and frequency-specific (r = 0.826, P < 0.001 and r = 0.870, P < 0.001) nocturnal wrist activities measured by DigiTrac. However, there was no correlation between BDNF or substance P and the subjective symptoms of pruritus or sleep-loss scores as reported by the parents in the SCORAD. In contrast, serum total IgE levels showed significant correlations with the subjective symptoms of pruritus (r = 0.576, P = 0.001) and sleep loss (r = 0.419, P = 0.027). CONCLUSIONS: Serum levels of BDNF and substance P correlate with the clinical score and quality of life score in patients with AD. The strong correlations with nocturnal wrist movements suggest that they may be the pathogenic factors of the annoying symptoms of scratching.     

Serum mucosa-associated epithelial chemokine (MEC/CCL28) in atopic dermatitis: a specific marker for severity

Background Mucosa‐associated epithelial chemokine (MEC; CCL28) is considered to be pivotal in mediating the migration of CC chemokine receptor 3‐ and 10‐ (CCR3‐ and CCR10)‐expressing, skin‐homing, memory, cutaneous lymphocyte‐associated antigen‐positive (CLA⁺) T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases, such as atopic dermatitis (AD). Aim This controlled longitudinal study was designed to evaluate the expression of CCL28 in serum in childhood AD and bronchial asthma (BA), and its possible relationship to disease severity and activity. Methods Serum CCL28 levels were measured in 36 children with AD, 23 with BA, 14 with both conditions, and 21 healthy age‐ and sex‐matched controls. Sixteen patients in the AD group were followed up and resampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables. Results Serum CCL28 levels in AD, whether during flare [median, 1530 pg/mL; mean ± standard deviation (SD) = 1590.4 ± 724.3 pg/mL] or quiescence (median, 1477 pg/mL; mean ± SD = 1575.2 ± 522.1 pg/mL), were significantly higher than those in healthy children (median, 301 pg/mL; mean ± SD = 189.6 ± 92.8 pg/mL); however, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median, 340 pg/mL; mean ± SD = 201.6 ± 109.5 pg/mL) were significantly lower than those in the AD group, and comparable with those in healthy controls. Serum CCL28 levels in severe AD were significantly higher than those in mild and moderate cases, and correlated positively with the calculated severity scores [Leicester Sign Score (LSS) and Scoring Atopic Dermatitis (SCORAD)]. CCL28 levels during the exacerbation of AD were positively correlated with the corresponding values during remission, the peripheral absolute eosinophil counts, and serum lactate dehydrogenase levels. Serum CCL28 levels were not correlated with the serum total immunoglobulin E values in AD. Conclusions Our data reinforce the concept that CCL28 might contribute to the pathogenesis of AD, probably through the selective migration and infiltration of effector/memory T‐helper‐2 cells in the skin. CCL28 may also represent an objective prognostic marker for disease severity. Further studies may pave the way for CCL28 antagonism among adjuvant therapeutic strategies.     

Plasma neuropeptides and perception of pruritus in psoriasis

The aim of this study was to evaluate the influence of selected neuropeptides on itching in psoriatic individuals. Fifty-nine patients (43 pruritic and 16 non-pruritic) with psoriasis were included in the study. The severity of psoriasis, measured using the Psoriasis Area and Severity Index scale, ranged between 2 and 43.7 points. The intensity of pruritus was evaluated using a Visual Analogue Scale. The plasma levels of substance P, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y were measured radioimmunologically. The plasma level of neuropeptide Y was significantly decreased in patients with pruritus compared with those without pruritus (21.6 +/- 39.6 pg/ml and 144.3 +/- 385.7 pg/ml, respectively; p=0.03). Levels of other neuropeptides did not differ significantly between pruritic and non-pruritic patients; however, a tendency to lower plasma levels of substance P and vasoactive intestinal peptide in patients with itching was noted. Moreover, a significant negative correlation was observed between pruritus severity and levels of substance P (r = -0.36; p=0.02), as well as between pruritus severity and plasma levels of vasoactive intestinal peptide (r = -0.34; p=0.03). The imbalance of neuropeptide activity in the sera of pruritic subjects may suggest a role for neuropeptides in perception of itching in psoriatic individuals.     

Severity of disease, rather than xerosis, correlates with pruritus in patients with atopic dermatitis

Background  Atopic dermatitis (AD) is a chronic, relapsing skin disease characterized by xerosis and pruritus. As pruritus is an unpleasant sensation and the associated scratching aggravates the skin eruption considerably, it is important to control this symptom when treating AD. Dry skin is generally considered to be a potential cause of pruritus in xerotic skin diseases, but a clear correlation between pruritus and atopic xerosis has not been demonstrated.
Aim  To examine the contribution of atopic xerosis to the development of pruritus in AD.
Methods  Twenty-two patients with AD (12 males and 10 females; mean age, 27.5 years) were examined. Xerosis and the severity of disease were evaluated using the Objective Severity Assessment of Atopic Dermatitis (OSAAD) and the SCORing Atopic Dermatitis (SCORAD) index, respectively. A modified SCORAD index was calculated by removing the symptoms potentially associated with pruritus (intensity of itching and insomnia) from the standard SCORAD index. Pruritus was evaluated using both a visual analog scale and the Verbal Itch Score.
Results  The severity of AD (modified SCORAD index) correlated better than atopic xerosis (OSAAD score) with both pruritus scores, possibly indicating that the use of appropriate anti-inflammatory agents may be helpful in controlling pruritus as well as skin eruption in AD.
Conclusion  Our data suggest that the severity of disease (or skin inflammation) provides a greater contribution than xerosis to the development of pruritus in AD.     

Serum measurement of interleukin‐31 (IL‐31) in paediatric atopic dermatitis: elevated levels correlate with severity scoring

Background Interleukin‐31 (IL‐31) is a novel T‐helper‐lymphocyte‐derived cytokine that plays an important role in human T‐cell‐mediated skin diseases. When overexpressed in transgenic mice, IL‐31 induces severe pruritus resembling eczema in humans. Serum IL‐31 was previously found overexpressed in adults with atopic dermatitis (AD). The novelty of this study is the use of a pediatric patient group as well as comparison of IL‐31 levels during flare and quiescence. Objective This case‐controlled longitudinal study was designed to determine the levels of IL‐31 in serum of AD children and its associations in relation to disease activity and severity. Methods Sera were obtained from 50 AD children and 40 healthy volunteers. IL‐31 levels were measured using a sandwich ELISA. All AD patients were followed up and re‐sampled for serum IL‐31 after clinical remission. Serum IL‐31 levels were correlated with AD disease activity and severity variables. Results Serum IL‐31 levels were significantly higher whether during AD flare [median, 1600; mean (SD) = 1457.8 ± 770.4 pg/mL] or quiescence (1040; 958.7 ± 419.5 pg/mL), than those in controls (220; 197.3 ± 91.9 pg/mL). Serum IL‐31 levels were significantly higher in the high disease severity group compared with the moderate or low severity group. Moreover, serum IL‐31 levels correlated positively with the calculated severity scores (LSS, SSS and SCORAD index). Conclusion The results of this study confirm the importance of IL‐31 in AD pathophysiology. Serum IL‐31 level is an objective reliable marker of AD severity in children. It may represent a novel target for antipruritic drug development.     

Are age‐specific high serum IgE levels associated with worse symptomatology in children with atopic dermatitis?

BACKGROUND: Atopic dermatitis (AD) is a distressing disease associated with excoriations, pruritus, sleep disturbance, and elevation of serum total immunoglobulin E (IgE) levels. OBJECTIVE: To evaluate whether serum IgE levels correlate with the symptomatology and plasma chemokine levels in children with AD. METHODS: AD patients aged younger than 18 years were recruited from the pediatric dermatology clinic of a university teaching hospital, and the AD severity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index. Concentrations of serum total IgE, eosinophil count, and plasma AD-associated chemokines [cutaneous T-cell-attracting cytokine (CTACK), thymus and activation-regulated chemokine (TARC)] were measured. RESULTS: One hundred and seventeen Chinese children with AD (64 boys and 53 girls), with an age (mean +/- standard deviation) of 10.7 +/- 4.4 years, were recruited. Their overall SCORAD index (mean +/- standard deviation) was 51.1 +/- 22.8. The total serum IgE level divided by the age-specific upper limit (AE) correlated well with the extent and intensity of AD, except for oozing/crusting, which was significant only in males. There was a significant correlation between AE and pruritus or sleep loss only in females. Levels of IgE, CTACK, and TARC, and eosinophil count, differed significantly between patients with mild, moderate, and severe disease. AE correlated well with TARC (r = 0.50, P < 0.001) and eosinophil count (r = 0.41, P < 0.001), but not with CTACK (r = 0.11, P = 0.270). The prediction of moderate to severe eczema by AE gave an area under the receiver-operating characteristic curve of 0.76 (95% confidence interval, 0.65-0.86; P = 0.004). An optimum positive predictive value of 94.2% was achieved with a cut-off point of AE of 2.95, sensitivity of 75.0%, and specificity of 66.7%. CONCLUSION: AE correlates significantly with various objective clinical scores and chemokine markers of AD, and is a useful indicator for predicting moderate to severe AD in children.     

Lesson from performing SCORADs in children with atopic dermatitis: subjective symptoms do not correlate well with disease extent or intensity

BACKGROUND: Atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. It is not known how well these symptoms correlate with the extent and intensity of eczematous involvement. We evaluated whether: (i) the level of sleep loss correlates with pruritus and (ii) the level of pruritus correlates with the extent or severity of AD in children according to the SCORing Atopic Dermatitis (SCORAD) index. METHOD: Patients with AD younger than 18 years old were recruited from the pediatric dermatology clinic of a university teaching hospital, and AD severity was evaluated by the SCORAD index. RESULTS: One hundred and eighty-two Chinese children with AD (107 boys and 75 girls) [mean (SD) age of 9.6 (4.2) years] were recruited. Their mean (SD) overall SCORAD was 30.1 (19.2). Sleep loss was strongly correlated with pruritus (r = 0.57, P < 0.001). However, the two subjective symptoms were only weakly correlated with the objective signs (extent and intensity) of AD. The correlations between pruritus and extent and intensity were 0.42 (P < 0.001) and 0.38 (P < 0.001), respectively, and the correlations between sleep loss and extent and intensity were 0.38 (P < 0.001) and 0.34 (P < 0.001), respectively. CONCLUSION: We speculate that the lack of a better correlation was either because pruritus and sleep loss as reported by parents were imprecise, or that mechanisms other than disease extent or severity are responsible for the pathogenesis of these subjective symptoms.     

Cyclic adenosine monophosphate phosphodiesterase activity in peripheral blood mononuclear leucocytes from patients with atopic dermatitis: correlation with respiratory atopy

We determined the cyclic adenosine monophosphate phosphodiesterase (cAMP-PDE) activity in peripheral blood mononuclear leucocytes from 100 patients with atopic dermatitis (AD) aged 13–57 years (mean ± SD, 29.8 ± 17.7 years). The correlation between cAMP-PDE activity and clinical parameters such as the severity of eczema and a personal or family predisposition to atopic respiratory diseases (ARD) (asthma or allergic rhinitis) was examined. Although the enzymic activity varied from normal to very high in the AD patients, cAMP-PDE activity was significantly ( P  < 0.005) elevated in AD patients (42.1 ± 22.0 units) as compared with the normal controls (12.4 ± 5.6) and clinical control subjects (13.4 ± 9.5). In contrast, we found no correlation between cAMP-PDE activity and the severity of eczema when AD patients were classified into four categories (remission, mild, moderate and severe) according to the extent of their skin involvement. Furthermore, we found that systemic corticosteroid therapy in severe AD patients did not alter the cAMP-PDE activity. cAMP-PDE activity was significantly ( P  < 0.01) higher in those AD patients who had a personal history of ARD (47.2 ± 11.2) than in AD patients with a family history of ARD (37.2 ± 17.4) and those without a personal or family history ('pure' AD) (34.4 ± 19.8). Nevertheless, the cAMP-PDE activity was significantly higher even in 'pure' AD patients than in the controls. These results suggest that an elevation of cAMP-PDE activity is closely related to a predisposition to respiratory atopy, and does not follow inflammation in AD patients.     

Questionnaire survey of the efficacy of emollients for adult patients with atopic dermatitis

Emollients are useful and important treatment adjuncts for patients with atopic dermatitis (AD). Heparinoid mucopolysaccharide creams or lotions are emulsion ointments for moisturizing the skin. The objective of this study was to investigate the view among adult AD patients regarding the effectiveness of emollients. We developed a questionnaire at our University Hospital to characterize how patients with AD viewed the efficacy of emollients. Patients were asked to participate prior to treatment and the questionnaire was given within 1 month of treatment. The severity of AD was graded as mild, moderate, severe or very severe. The severity scoring was performed only when the participants answered the questionnaire. Of the 110 enrolled AD patients, 103 returned the completed questionnaires. Ninety-eight patients (95.1%) used heparinoid mucopolysaccharide creams or lotions. There was a strong correlation between their view of the efficacy of the emollient and the condition of dry skin, pruritus and eczematous skin. There was a significant correlation between AD severity and the perceived efficacy of the emollient for dry skin, pruritus and eczematous skin. There was a greater sense of efficacy among patients with milder AD than in more severe AD cases. Patients who felt sufficient efficacy of the emollient for pruritus were significantly older than those who felt there was no efficacy. In addition, the age of onset of AD was significantly higher among those who felt sufficient efficacy for pruritus compared to those who felt little efficacy. We speculate that the efficacy of emollients could be demonstrated in the treatment of milder AD, but may only have partial efficacy in more severe cases. Emollient therapy might have lower efficacy for pruritus among younger or earlier onset AD patients.     

Detection of the levels of neuropeptides, ACTH and cortisol in the blood of patients with polymyositis/dermatomyositis and their significance

Recent research has shown that the neuroendocrine system can regulate the function of the immune system and that ACTH and cortisol play important roles in maintaining the immune homeostasis. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with unclear pathogeneses closely related with immune disorders, so we detected the levels of neuropeptide Y (NPY), beta-endorphin (beta-EP), calcitonin gene-related peptide (CGRP), adrenocoricotropic hormone (ACTH), and cortisol in blood of patients with PM/DM to investigate the relationship between these indices and the pathogenesis of PM/DM. The detection of NPY, beta-EP, CGRP, and ACTH concentrations in plasma and cortisol in serum of 28 cases of PM/DM was carried out using radioimmunoassay methods, and the results were compared with those of 20 normal controls. The levels of NPY in the plasma of PM/DM was significantly higher than those of the controls, while beta-EP, CGRP and ACTH were significantly lower than those of the controls, and cortisol was not significantly different before treatment. Linear correlation analysis indicated that NPY was significantly positively correlated with CPK, and beta-EP and CGRP were significantly negatively correlated with CPK. There were no significant correlations among cortisol ACTH, and CPK and no significant correlations between NPY, beta-EP, CGRP, ACTH, cortisol and age or duration of disease before treatment. After treatment for three months, NPY, beta-EP and CGRP tended to become normal and no longer significantly different from the control values. However, ACTH fell further and was significantly lower than the level before treatment. Therefore the increase in NPY and the decreases in beta-EP, CGRP, and ACTH in the plasma of PM/DM patients may be related to the pathogenesis of PM/DM.     

Impact of pruritus on quality of life in sulfur mustard-exposed Iranian veterans

Background  Sulfur mustard, a chemical warfare agent, has various verified chronic effects on the skin. One of the foremost negative impacts of this agent is chronic pruritus, which plagues chemically injured veterans for life and can downgrade their quality of life.
Aim  To assess the association between the quality of life and pruritus severity in chemically injured veterans.
Methods  One hundred and twenty-five consecutive chemically injured veterans suffering from pruritus were assessed via the Dermatology Life Quality Index (DLQI) and pruritus score. Pruritus scores less than 15, between 16 and 30, and more than 30 were considered as mild, moderate, and severe pruritus, respectively. Patients with different levels of pruritus were compared with respect to their DLQI and its subscores.
Results  All subjects were male with a mean age of 44.3 ± 8.0 years; 11.2% had mild, 35.2% moderate, and 53.6% severe itching. The DLQI median scores in the mild, moderate, and severe cases were 16, 20, and 21, respectively ( P  = 0.014). The DLQI subscores of symptoms and feelings ( P  = 0.015), personal relationships ( P  = 0.002), and daily activities ( P  = 0.036) were worst in patients with severe itching.
Conclusion  Chemically injured veterans suffering from severe itching have a significantly poorer quality of life than do patients with milder symptoms.     

Severity scores, itch scores and plasma substance P levels in atopic dermatitis treated with standard topical therapy with oral olopatadine hydrochloride

Atopic dermatitis (AD) is a common chronic or chronically relapsing, severely pruritic, eczematous skin disease. Recently, substance P (SP) has been demonstrated to be one of the important neuropeptides for mediating itch–scratch and stress–scratch cycles. In this study, we examined the severity scores, itch scores and plasma SP levels in 19 patients with AD treated with standard topical therapy with or without an oral antihistamine, olopatadine hydrochloride, for 4 weeks. The standard therapy decreased SCORAD scores, itch behavioral rating scores and plasma SP levels at post-treatment in the mass, but the topical therapy with olopatadine was more effective than the topical therapy alone, suggesting a potential additive effect.     

Oral antihistamine therapy influences plasma tryptase levels in adult atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is an allergic skin disease that follows a clinical course of 'flare-up' and remission. Histamine and tryptase are inducers of pruritus and non-sedating second-generation antihistamines, including fexofenadine, are widely used for treatment of allergic skin disorders. OBJECTIVE: We assessed the efficacy of a second-generation antihistamine in AD patients and examined its pharmacological effects on chemical mediators. METHODS: The scoring atopic dermatitis (SCORAD) instrument and visual analogue scale (VAS) for pruritus were used to assess disease severity in 349 AD patients. Twenty patients with moderate AD symptoms, who had not received any treatment for 2 weeks, were randomly assigned into two groups. Ten patients underwent fexofenadine and emollient treatment (Group 1) and 10 received fexofenadine and steroid treatment (Group 2) for 1 week. SCORAD and VAS for pruritus, and blood histamine and tryptase levels were evaluated before and after treatment. RESULTS: SCORAD and VAS improved in both Group 1 (p=0.01 and p=0.006, respectively) and Group 2 (p<0.001 and p=0.001, respectively). The improvement in Group 1 showed a significant correlation with the diminution rate of blood tryptase levels (SCORAD: r=0.83 and p=0.013, respectively; VAS: r=0.81, p=0.015, respectively). End-point plasma tryptase levels were significantly lower than baseline levels in Group 2 (p=0.046). Histamine levels did not show any significant changes in either group. CONCLUSION: These results suggest that second-generation antihistamine therapy reduces AD pruritus, resulting in the effective clinical treatment for AD. In addition, monitoring tryptase levels during antihistamine therapy in moderate AD treatment may prove to be useful in establishing treatment effects.     

白癜风患者血浆三种神经肽测定及其临床意义

目的：β内啡肽（β－EP）、神经肽Y（NPY）及降钙素基因相关肽（CGRP）是重要的神经递质,同时也可作为免疫调节因子发挥作用。本研究旨在观察这些神经肽是否可能与白癜风的发病有关。方法：用放射免疫分析法测定40例白癜风处于进展期或稳定期的不同类型患者血浆3种神经肽浓度,并与23例正常对照作比较。结果：寻常型（局限性与泛发性）、节段型、进展期和稳定期白癜风患者血浆β－EP、NPY水平均较正常对照组显著增高;进展期白癜风NPY比稳定期显著提高;泛发性及进展期白癜风血浆CGRP比正常对照组显著增高。结论：结果表明上述三种神经肽与白癜风的发病可能存在一定关系,开发神经肽拮抗剂对于白癜风的治疗可能成为一种新的途径。     

儿童特应性皮炎患者外周血单一核细胞IL-31与疾病严重程度相关性分析

目的 探讨IL-31在儿童特应性皮炎发病机制中的作用以及与特应性皮炎瘙痒的相关性。方法 22例特应性皮炎患儿与22例健康儿童外周血单一核细胞在葡萄球菌肠毒素B（SEB）刺激或非刺激状态下，应用实时PCR方法分析IL-31表达情况；酶联免疫吸附法测定其血清IgE水平；对患儿病情进行病情严重程度评分，分析IL-31 mRNA与IgE水平、疾病严重程度及瘙痒的相关性。结果 特应性皮炎患儿外周血单一核细胞IL-31表达显著增加，是对照组的23.2倍（P < 0.01）。特应性皮炎组和对照组外周血单一核细胞受SEB刺激后IL-31表达均有不同程度升高，以特应性皮炎组IL-31表达增加更显著，是对照组的20.44倍。患儿血清总IgE水平中位数为260.05 IU/mL（范围5.9 ～ 1131.01 IU/mL），对照组为17.7 IU/mL（范围5 ～ 140.7 IU/mL），两组比较，P < 0.01。IL-31与患儿病情严重程度以及血清总IgE水平无显著相关性（r = 0.07，P > 0.05；r = 0.22，P > 0.05）。结论 IL-31可能参与儿童特应性皮炎发病，其作用机制可能不依赖血清IgE；SEB能诱导正常人外周血单一核细胞快速表达IL-31，是IL-31产生的重要调节因素。     

Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus

Substance P and its receptor(R) neurokinin (NK)-1 may have a role in the pathogenesis of psoriasis. Stress has been reported to play a role in the onset and exacerbation of psoriasis, which might include the substance P-NK-1 receptor(R) pathway. A feature of psoriasis, that has been correlated to the severity of stress and secretion of substance P, is pruritus. The objective of this study was to investigate the expression of substance P and the NK-1R in involved and noninvolved psoriatic skin, using a biotinylated streptavidin technique. Moreover, a possible correlation between the patient′s level of chronic stress, measured by salivary cortisol samples, degree of lesional pruritus, measured by means of a visual analogue scale, and the expression of substance P- and the NK-1R, was investigated. There was a low number of substance P positive nerve fibres in noninvolved and involved skin, the major immunoreactivity for substance P being found in inflammatory cells. The number of substance P- and NK-1R positive inflammatory cells was increased in involved compared to noninvolved psoriatic skin. The substance P positive cells were mostly lymphocytes, while most of the NK-1R positive cells were mast cells. NK-1R immunoreactivity was also seen as a reticular pattern in the upper part of the epidermis of involved skin in the majority of the patients. Low cortisol ratios in the patients, being an indicator of chronic stress, were correlated to an increased number of substance P- and NK-1R positive inflammatory cells in noninvolved psoriatic skin, and higher cortisol ratios to the presence of keratinocyte NK-1R immunoreactivity in involved skin. The degree of pruritus could not be correlated to the number of substance P positive fibers nor cells. Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress.