Soluble intercellular adhesion molecule-1 and soluble E-selectin levels in patients with atopic dermatitis

Summary The serum levels of soluble intercellular adhesion moIecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined by double determinant immunoassay (DDIA), in 57 patients with atopic dermatitis (AD) and 31 age- and sex-matched healthy control subjects. Both sICAM-1 and sE-selectin levels were significantly higher in patients with AD than in healthy controls (P< 0.01). and were correlated with disease severity. A longitudinal study of patients with AD revealed that the levels of sICAM-1 decreased in those in whom symptoms improved. The sICAM-1 levels were significantly correlated with those of sE-selectin. Our studies suggest that such high levels of serum sICAM-1 and sE-selectin may affect the immune response in patients with AD. The levels of sICAM-1 and sE-selectin may be a useful immunological parameter for monitoring disease activity in AD.     

Soluble E-selectin, other markers of inflammation and disease severity in children with atopic dermatitis

E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are membrane-bound adhesion molecules which mediate the attachment of leucocytes to endothelial cells. These molecules are preferentially expressed on activated endothelium. The soluble forms of these molecules (sE-selectin, sP-selectin, sICAM-1 and sVCAM-1) are present in the circulation as a result of shedding. Some of the soluble adhesion molecules have been thought to reflect disease activity in atopic dermatitis (AD). To evaluate their potential to reflect disease activity in AD, we correlated their plasma concentration with clinical severity measured by objective SCORAD (SCORing Atopic Dermatitis). Furthermore, levels of total IgE, specific IgE, and eosinophil cationic protein (ECP) were determined. SCORAD and sE-selectin levels were significantly increased in children with specific IgE for both food and inhalation allergens ( P  < 0.05). ECP consistently showed an increase with the scores of SCORAD, but no statistical significance was reached. Disease activity was significantly correlated with the plasma levels of sE-selectin ( r _s = 0.6, P  < 0.0005) but not with sP-selectin, sICAM-1 and sVCAM-1. This agrees with recent studies performed in adults with AD, and supports the potential of sE-selectin as a parameter for monitoring disease activity in young children with AD.     

Soluble CD30 plasma concentrations correlate with disease activity in patients with atopic dermatitis

The levels of soluble CD30 in 79 patients with atopic dermatitis were compared with those found in 54 patients with psoriasis and 36 control individuals (no psoriasis, no atopic dermatitis). In relation to the control group, patients with atopic dermatitis were found to exhibit an increased concentration of sCD30 of at least 1.5-fold (p < 0.001). In addition, sCD30 concentrations were shown to correlate with the severity of the disease as measured by the score index for atopic dermatitis and different stages of disease activity, such as acute, subacute, or chronic forms, and localized or generalized distribution of atopic dermatitis. The application of topical glucocorticoid therapy for a period of 2 weeks resulted in a decrease in the level of sCD30 by 46% in 8 patients, especially in the acute, generalized form of atopic dermatitis. Psoriasis patients showed no significant differences in sCD30 levels in relation to the control group. This study demonstrates a correlation between sCD30 concentration and the activity of the disease and therefore suggests sCD30 as a prognostic marker, being superior to predictions from measurements of IgE or eosinophil cationic protein.     

Moderate correlation between quality of life and disease activity in adult patients with atopic dermatitis

Background Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before (t = 0) and after 6 weeks (t = 6) of treatment with cyclosporin 5 mg/kg. Methods In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), ‘rule of nines’ extent score and serum levels of thymus and activation‐regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed. Results At t = 0 there was a small, non‐significant correlation between the DLQI and the objective SCORAD, ‘rule of nines’ or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the ‘rule of nines’ score showed moderate and significant correlations with the DLQI (r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P < 0.001). An individual’s improvement in disease activity (objective SCORAD, SASSAD and ‘rule of nines’) with 10 points was associated with an improvement of 1.3, 1.5 and 1.1 points respectively in DLQI. Conclusions Disease activity correlated better with QoL when disease activity was less severe and disease extent (‘rule of nines’) correlated better with QoL than disease severity. An individual’s improvement of 10 points in disease activity was accompanied by only a small improvement in QoL. Other factors than disease activity may influence QoL in patients with AD.     

Soluble E-selectin serum levels correlate with disease activity in psoriatic patients

E-selectin is an adhesion molecule expressed on vascular endothelial cells in several inflammatory skin diseases, including psoriasis. It is responsible for the adherence between microvascular endothelium and neutrophils, monocytes, eosinophils and subsets of T cells. Soluble E-selectin (sE-selectin) serum levels were measured by ELISA in 32 psoriatic patients before treatment and compared with both post-treatment sE-selectin levels in 16 patients and sE-selectin values in 10 healthy individuals. Soluble E-selectin serum levels were significantly increased in psoriatic patients compared with healthy persons. Moreover, a significant correlation was demonstrated between sE-selectin values and PASI scores. No relationship was found between sE-selectin levels and duration of psoriasis. Soluble E-selectin serum levels decreased significantly after treatment of psoriasis. This phenomenon was more evident in patients with more severe psoriasis. In conclusion, sE-selectin serum levels correlate with the extent of psoriatic lesions and could be used as marker of the disease activity in psoriatic patients.     

Eosinophil cationic protein in sera of patients with atopic dermatitis

Patients with atopic dermatitis frequently show elevated blood eosinophil counts, and eosinophil-derived major basic protein has been demonstrated in the eczematous skin from patients with atopic dermatitis. To evaluate further the role of eosinophils in the pathogenesis of atopic dermatitis, the concentration of eosinophil cationic protein was measured in serum samples of 42 patients with moderate to severe disease. The results were compared with those obtained in 32 patients with psoriasis with (n = 9) or without (n = 23) a history of inhalant allergy, 12 patients with a history of pseudoallergic reactions to acetylsalicylic acid, 14 patients with a history of inhalant allergy, and 31 nonatopic healthy control subjects. Eosinophil cationic protein levels were significantly increased in the serum of patients with atopic dermatitis (p less than or equal to 0.005) and patients with a history of pseudoallergic reactions to acetylsalicylic acid (p less than or equal to 0.01). There was no significant difference between eosinophil cationic protein levels in patients with psoriasis or a history of inhalant allergy and in control subjects. Moreover, eosinophil cationic protein levels did not differ significantly in psoriasis patients with or without inhalant allergy. These studies support the concept of an active participation of eosinophils in atopic dermatitis and point to a possible role for eosinophils in pseudoallergy.     

The concept of disease in patients with atopic dermatitis

34 former patients of a dermatological department with atopic dermatitis were compared with 29 patients of an Ear-Nose-Throat-department having similar age, sex and occupation and showing hardly any psychosomatic disturbances. Contrary to our expectations, the empiric-psychological examination did not reveal any impairment of the social behavior or the emotional competence of patients suffering from atopic dermatitis. In comparison to the control group, the patients of the dermatological department attached significantly greater importance to psychological influences on development as well as treatment of the disease. There was a correlation between symptoms "coming from outside" and the social competence; however, this correlation was not significantly greater than the control group. Our investigations suggest that atopic dermatitis may be differentiated into somatical-organizing types and rather psychological-organizing types. The second group shows uncertainties with regard to the social competence.     

Elevated levels of interleukin 2 receptor in sera of patients with atopic dermatitis and psoriasis

Elevated levels of serum interleukin 2 receptor (IL2R) represent an early measure of T cell activation. The concentration of IL2R was measured in the sera of patients with atopic dermatitis (n = 58) or psoriasis, without psoriatic arthritis, (n = 26), who had moderate to severe disease activity, and in non-atopic healthy controls (n = 37) by an ELISA technique. Serum IL2R levels were found to be significantly elevated in both disease groups compared with the controls. The increase in serum IL2R may be due to T cell activation in the dermis.     

特应性皮炎患者血清维生素D检测及其临床意义

目的 检测特应性皮炎（AD）患者血清中维生素D（VitD）、总免疫球蛋白E（tIgE）、白细胞介素4（IL?4）、IL?6水平,评价VitD与AD患者病情严重程度的关系及其在AD发病中炎症与免疫调节中的作用。方法 采集37例AD组和30例对照组外周血,检测血清VitD、tIgE、IL?4、IL?6水平,通过SCORAD评分评估AD患者病情严重程度。采用t检验或U检验分析组间差异,采用χ2检验比较VitD缺乏、不足与充足患者比例,采用Pearson或Spearman相关进行各组间的相关性分析。结果 AD组血清VitD水平［（24.77 ± 9.29） μg/L］低于对照组［（28.98 ± 6.87） μg/L,t = 2.015,P = 0.048］,tIgE水平［137.68（37.59 ~ 414.53） IU/ml］高于对照组［45.16（14.56 ~ 112.12） IU/ml,Z = -3.399,P = 0.001］,IL?4水平［（8.86 ± 4.83） ng/L］高于对照组［（4.78 ± 3.07） ng/L,t = 4.147,P < 0.001］,IL?6水平［6.53（3.99 ~ 15.30） ng/L］高于对照组［4.58（2.85 ~ 8.17） ng/L,Z = -2.173,P = 0.030 ］。AD组SCORAD评分与血清VitD水平负相关（r = -0.505,P = 0.001）,与tIgE、IL?4水平正相关（r值分别为0.531、0.519,P值均为0.001）,与IL?6无相关性（r = -0.139,P = 0.411）。AD组与对照组相比,VitD缺乏、不足与充足患者比例差异有统计学意义,χ2 = 8.762,P = 0.013。VitD缺乏患者血清tIgE［2846.87（319.02 ~ 7300.00） IU/ml］与IL?4水平［（16.37 ± 2.05） ng/L］分别高于VitD不足［110.07（26.20 ~ 501.48） IU/ml,P = 0.045;（8.28 ± 4.48） ng/L,P = 0.011］和VitD充足患者［123.93（91.61 ~ 273.68） IU/ml,P = 0.024;（8.00 ± 4.63） ng/L,P = 0.041］。VitD缺乏患者IL?6水平［15.10（8.49 ~ 30.72） ng/L］高于充足［6.22（4.47 ~ 9.47）ng/L,P = 0.011］。结论 AD患者存在VitD缺乏或不足,VitD缺乏与高水平tIgE、IL?4、IL?6有关,且AD的严重程度与tIgE、IL?6升高及VitD降低关系密切。     

Comparison of different activity parameters in atopic dermatitis: correlation with clinical scores

BACKGROUND: Several laboratory markers have been described to correlate positively with disease activity of atopic dermatitis (AD). These include soluble adhesion molecules and eosinophil granular proteins. Although the correlation of these parameters with the severity and extent of skin involvement has been repeatedly studied in the past, no systematic investigation has been performed over a lengthy period of time. In addition, no subjective disease parameters recorded by the patient have been included in studies dealing with disease activity. OBJECTIVES: To assess the validity of different objective and subjective parameters [soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), eosinophil cationic protein (ECP), urinary nitrate excretion (reflecting endogenous nitric oxide formation) and the patients' impressions of pruritus, sleeplessness and skin status] as markers of AD disease activity. METHODS: Twenty patients were examined for 1 year and their skin status was evaluated by an established score (SCORAD). sE-selectin, sVCAM-1 and ECP were analysed by commercial test kits. Urinary nitrate concentration was measured by gas chromatography-mass spectrometry. The subjective parameters, pruritus, sleeplessness and impression of skin status, were recorded by the patients on a visual analogue scale. RESULTS: In this long-term trial, only sE-selectin and the subjective parameters showed a statistically significant correlation with the SCORAD score. CONCLUSIONS: Our data indicate that basic clinical scoring remains a most effective and relevant method of recording skin disease activity in AD.     

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.     

Soluble E-selectin and eosinophil cationic protein are distinct serum markers that differentially represent clinical features of atopic dermatitis

The serum levels of eosinophil cationic protein (ECP), soluble E-selectin (sE-selectin), soluble CD14 (sCD14) and interleukin (IL)-4 are known to be elevated in patients with atopic dermatitis (AD). However, little is known of the mutual relationship between these factors. To elucidate the clinical and mutual relevance of these markers, we examined the serum levels of ECP, sE-selectin, sCD14 and IL-4 as compared with eruption scores, itch scores, total IgE and numbers of peripheral eosinophils in patients with AD (n = 43), non-atopic eczema (n = 24) and urticaria (n = 13) and in normal individuals (n = 45). In 27 patients with AD the levels of these markers were compared before and after treatment. Levels of ECP were elevated only in the patients with AD, whereas the sE-selectin levels were higher not only in AD but also in non-atopic eczema in a severity-dependent manner. The levels of both markers significantly diminished after treatment. Significant correlations existed between ECP levels and numbers of eosinophils, sE-selectin levels and itch scores, and sE-selectin levels and IgE levels. No significant changes were observed in the sCD14 and IL-4 levels. Taken together, sE-selectin and ECP are good but distinct serum markers that reflect different clinical features of AD.     

Immunological parameters in the sera of patients with atopic dermatitis and airborne allergy treated with allergy vaccines

Patients with atopic disorders present an increased production of IgE, which is usually limited to specific antibodies against various environmental allergens. It has also been suggested that the production of these antibodies may be influenced by effective specific immunotherapy (SIT). Of course, a decline of serum antigen specific IgE in the course of such a treatment cannot explain the clinical efficacy of SIT and is probably not a key mechanism. However, SIT may at least participate in the final clinical result. In this study, 37 patients with atopic dermatitis were treated with allergy vaccines (Novo-Helisen Depot) for a time period of 48 months. The control group consisted of 29 patients with atopic dermatitis who were treated with classical methods. The clinical score (W-AZS), total IgE and antigen specific IgE (asIgE) in the sera of patients were assessed before treatment and after 24 and 48 months of therapy (FEIA CAP System, Pharmacia). There was a significant difference between the two investigated groups from both the clinical and immunological standpoints after 2 and 4 years of observation. There was a significant decrease of serum total IgE and asIgE (directed against airborne allergens) in the course of specific immunotherapy. In the control group, the total IgE level tended to increase, and this tendency was also recorded in case of asIgE measurements. We also evaluated the influence of specific immunotherapy on the serum level of IFN-G, sIL-2R, IL-4, IL-5 and IL-10 before treatment and after 4 years of therapy with the quantitative 2-step colorimetric sandwich ELISA method (R and D Systems). In the group of patients treated with allergy vaccines, a significant decrease of the serum sIL-2R level was observed after 48 months of therapy (p<0.01). In the control group, a significant increase of serum IL-4 (p<0.01) as well as IL-5 (p<0.05) was registered at the end of the observation period. There was no significant correlation between the clinical score and serum level of any of the investigated cytokines in either group of patients before the treatment or after 48 months of therapy.     

The disease burden of pediatric patients with atopic dermatitis in Japan

Background

Atopic dermatitis (AD) is a chronic skin condition that is associated with significant patient burden and decreased health-related quality of life (HRQoL). We report results of the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience study in Japanese pediatric patients, focusing on the impact of AD severity on disease burden.

Methods

Children and adolescents aged 6 months to 17 years (or their caregivers/parents) completed an online survey between September 26, 2018, and March 5, 2019. Patients with diagnosed AD (i.e., met International Study of Asthma and Allergies in Childhood criteria and had a self-reported AD diagnosis) were evaluated for disease severity using the Patient-Oriented Eczema Measure (POEM). Impact of AD severity on AD symptoms (itching, pain, and sleep disturbance), disease flares, atopic comorbidities, healthcare resource utilization, school days missed, and HRQoL were assessed.

Results

Of 5702 Japanese pediatric patients, 547 had diagnosed AD and were included in this analysis. Based on POEM scores, AD severity was clear/mild in 346 patients (63.3%), moderate in 177 (32.5%), and severe in 24 (4.4%). Across all age groups (i.e., less than 6, 6–11, and 12–17 years), increased AD severity was associated with increased AD symptom severity, number of flares, atopic comorbidities, healthcare resource utilization, and school absences, as well as worsened HRQoL.

Conclusions

This population-based study of Japanese children and adolescents showed that greater AD severity had a high impact on disease burden.     

Leukoderma in patients with atopic dermatitis

Atopic dermatitis (AD) is occasionally associated with vitiligo, however, the incidence and conditions of vitiligo or leukoderma, and the characteristics of concurrent AD, remain unclear. We conducted a prospective observational study to investigate the leukoderma‐related clinical manifestations and bioparameters of AD. Because vitiligo in AD lesions is occasionally associated with inflammation, we used leukoderma in this study. Enrolled were all AD patients who had been followed up in our AD outpatient clinic and visited within the previous 4 months. During this period, we carefully inspected whether the patients had leukoderma. Eight of 52 patients had leukoderma (15.4%) and were designated as the leukoderma group, and the remaining 44 patients comprised the non‐leukoderma group. While the ages were statistically not different between the two groups, female preponderance was significantly observed in the leukoderma group. The leukoderma patients tended to have higher values of SCORAD, CCL17/thymus and activation regulated chemokine and lactate dehydrogenase than the non‐leukoderma patients. The leukoderma group was also characterized by a lower frequency of allergic rhinitis and a higher frequency of prurigo lesions. Thus, despite the possession of high AD severity, the leukoderma patients may possibly retain a relatively T‐helper 1‐skewing state in relation to the development of leukoderma and less association with rhinitis.