Investigation of cytokine levels and their association with SCORAD index in adults with acute atopic dermatitis

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing frequency over the last decades, especially in adults. Cytokines orchestrate atopic skin inflammation. Objectives The aim of this study was to compare serum levels of cytokines in adult patients with acute AD (AD1) with other groups of AD patients and controls and investigate the possible association between such cytokines and disease severity. Methods We measured cytokine levels using flow cytometry in 21 adult patients with acute AD, 12 adults with chronic AD, 10 children with acute AD and 10 healthy adults. Results Flow cytometry analysis of cytokines revealed that interleukin 10 (IL‐10), IL‐6, interferon γ (IFN‐γ) and IL‐4 levels were significantly decreased in AD1 group compared with controls, whereas IL‐2 and tumour necrosis factor (TNF) did not differ. Comparison of AD1 group with adults chronic phase group showed that IgE, eosinophil and IL‐2 levels remained unaltered, whereas IL‐10, IL‐6, IFN‐γ, IL‐4 and TNF were significantly decreased. SCORAD and IgE levels were significantly increased, IL‐10, IL‐6 and IFN‐γ were decreased and TNF, IL‐2, IL‐4 and eosinophil levels remained unchanged in AD1 group compared with children acute phase group. Within AD1 group correlation analysis revealed that IgE and TNF levels were significantly associated with AD severity. Coefficient of determination analysis revealed that TNF and IgE levels could explain 49.14% and 35.28% of the variance of SCORAD. Conclusions These data indicate that serum IgE and TNF levels correlate with AD severity and that serum cytokines are downregulated in AD1 group. Further studies are clearly needed to elucidate cytokines’ role in adults with AD .     

Contact allergy to aeroallergens in children with atopic dermatitis: comparison with allergic contact dermatitis

Immediate and delayed cutaneous hypersensitivity are believed to be implicated in the physiopathology atopic dermatitis (AD). The purpose of this study was to evaluate Type I and Type IV allergy to aeroallergens in children with AD. 59 children (mean age 5.2 years), presenting with AD according to Hanifin and Rajka's criteria, were skin tested (patch and corresponding prick tests) with common environmental aeroallergens and a restricted panel of the European standard series over a 1-year period. History and clinical data were carefully recorded using a standardized evaluation sheet: total and specific IgE serum levels were evaluated 17 of 59 patients (28.8%) had at least 1 positive patch test, 32 of 59 patients (54.2%) had at least 1 positive prick test. Corresponding patch and prick tests were observed in 8 out of 17 patients. 5 children with positive patch tests had negative prick tests. Irritant pustular reactions (2/59, i.e. 3%), "angry back" reactions (6/59, i.e. 10%) and doubtful reactions (3/59, i.e. 5%) were excluded from the positive group. Positive patch tests observed included, in decreasing order: D. pteronyssinus and D. farinæ (26.8%) garden trees (12.2%), plantain (9.8%), timothy grass, mugwort and damp area trees (4.9% each), and orchard grass (2.44%). 6 children with positive aeroallergen patch tests and 11 children with negative aeroallergen patch tests had at least 1 positive patch test to standard allergens. All children with an irritant reaction to aeroallergens had no reaction to standard patch tests. The relevance of aeroallergens in upgrading the severity of AD lesions has still to be explored by challenge studies and by long-term follow-up.     

Bicentre experience in the treatment of severe generalised atopic dermatitis with extracorporeal photochemotherapy

Pilot studies have shown an improvement of atopic dermatitis in approximately 65% of patients during extracorporeal photopheresis (ExP) therapy. The purpose of the present clinical trial was to investigate the response to ExP by controlling clinical and laboratory parameters during short term ExP therapy in patients with severe generalised atopic dermatitis. Thirty-five patients with severe, therapy-resistant atopic dermatitis were treated with ExP in an open clinical trial at two week intervals over a period of 6 to 10 cycles. Disease activity was measured before each cycle by SCORAD index together with a standardized protocol for blood samples. ExP led to a significant decrease (p < 0.05) in SCORAD from 74.4 +/- 15.5 before to 36.8 +/- 16.8 after ExP therapy (mean 10 cycles). Approximately 70% (24/33 patients = responder) of patients had a favourable response to ExP requiring at least 6 cycles. The decrease in SCORAD was accompanied by a significant decrease of eosinophil cationic protein (27%), sE-selectin (37%) and sIL-2R (53%) levels in serum (p < 0.05). No significant correlation between a decrease in these levels and values of blood eosinophils or lymphocytes was found (p > 0.05). In comparison to responders, most non-responders were characterised by very high levels of total IgE before and during therapy (p < 0.05). The present clinical trial confirms that short term ExP is an effective treatment for certain patients with severe atopic dermatitis based on anti-inflammatory mechanisms. Total IgE could be a predictor of outcome in ExP treatment.     

Nocturnal wrist movements are correlated with objective clinical scores and plasma chemokine levels in children with atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. Scratching due to pruritus is an important mechanism in the exacerbation of AD but is difficult to document in the home environment. OBJECTIVES: To evaluate whether nocturnal wrist activities, defined as average acceleration in the early hours of sleep, were correlated with components of the SCORing Atopic Dermatitis (SCORAD) index and various AD-associated chemokine markers. METHODS: Patients with AD aged under 18 years were recruited and the severity of eczema was assessed with the SCORAD index. Concentrations of plasma AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK); macrophage-derived chemokine (MDC); thymus and activation regulated chemokine (TARC)], interleukin (IL)-18, serum total IgE, and eosinophil counts were measured in these patients. Healthy children with noninflammatory and nonitchy skin conditions as well as healthy children of staff volunteers were recruited as controls. All children were instructed to wear the DigiTrac monitor on their dominant wrist before sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning. RESULTS: Twenty-four Chinese children with AD (mean +/- SD age 12.6 +/- 3.7 years) and 15 normal children (mean +/- SD age 11.9 +/- 3.4 years) were recruited. The median (interquartile range) SCORAD was 54.8 (32.8-70.2). Plasma concentrations in pg mL(-1) of CTACK, MDC, TARC and IL-18 in the patients were 105 (92-172), 1648 (973-4214), 258 (100-850) and 415 (304-539), respectively. When compared with controls, most wrist activities occurred at frequencies between 1 and 3 Hz. These activities were most consistent over the first 3 h of sleeping and correlated significantly with disease severity, extent, intensity, and AD-associated chemokine markers CTACK, MDC and TARC. However, there was no significant correlation between wrist activities and the subjective symptom of pruritus or sleep loss. CONCLUSIONS: This is the first study to demonstrate that wrist activities, nonintrusively measured by the DigiTrac monitor at home, are closely correlated with the objective clinical scores and levels of peripheral blood chemokine markers for AD but not with the reported symptoms of pruritus or sleep loss. We propose that wrist activities between 1 and 3 Hz for the first 3 h are a good indicator of AD severity in children and should substitute for the pruritus and sleep-loss components of the SCORAD.     

Results of atopy patch tests with house dust mites in adults with ''intrinsic'' and ''extrinsic'' atopic dermatitis

BACKGROUND: The most frequently employed diagnostic criteria of atopic dermatitis (AD) can be fulfilled in the absence of elevated total circulating IgE or specific IgE to food allergens or environmental aeroallergens and/or in the absence of personal or familial history of atopy as well. Therefore a distinction between 'extrinsic' or 'allergic' and 'intrinsic' or 'non-allergic' AD has been suggested. Recently, a patch test with environmental aeroallergens, named atopy patch test (APT), has been proposed for use in the study of AD. OBJECTIVE The aim of this study was to investigate the reactivity to APT in patients with 'extrinsic' and 'intrinsic' AD. PATIENTS, MATERIALS AND METHODS: Two groups of adult male subjects with AD were examined consecutively in our department (Department of Dermatology, Italian Navy Main Hospital, Taranto, Italy) andpatch tested with whole bodies of house dust mites (HDM) at a concentration of 20% in petrolatum (Dermatophagoides pteronyssinus 50%, D. farinae 50%). The groups included: (i) 95 patients affected by the adult clinical form of 'extrinsic' AD; (ii) 12 patients affected by the adult clinical form of 'intrinsic' AD; and (iii) a control group of 49 adult healthy male subjects with a negative anamnesis for eczema and atopy and negative skin prick test to aeroallergens/food allergens and/or normal level of total circulating IgE, also patch tested with the same allergen. The statistical differences were calculated by chi2 test and 95% confidence intervals (CI) were provided. RESULTS: The APT was positive in 47.4% (CI: 37-57%) of'extrinsic'AD, in 66.6% (CI: 41-93%) of'intrinsic' AD and in 12.2% (CI: 3-21%) of healthy subjects. The differences between the two AD subgroups and the control group were statistically significant (P < 0.001). CONCLUSIONS: APT positivity is more frequent in both 'extrinsic' and 'intrinsic' AD than in unaffected subjects. Other studies are needed to confirm our data and to explain why the APT is positive in the 'intrinsic' form.     

Serum levels of soluble stem cell factor and soluble KIT are elevated in patients with atopic dermatitis and correlate with the disease severity

BACKGROUND: Mast cell infiltration in skin lesions of atopic dermatitis (AD) is considered to play an important role in the pathogenesis of the disease. The most common factor that stimulates mast cell growth, migration and differentiation is stem cell factor (SCF), and the interaction of SCF and its receptor, KIT (tyrosine kinase transmembrane receptor), appears to be the key event in the recruitment and proliferation of mast cells. OBJECTIVES: To determine whether any altered metabolism of SCF and/or KIT is present in patients with AD. METHODS: We measured serum levels of soluble SCF (sSCF) and soluble KIT (sKIT) using enzyme-linked immunosorbent assay in 54 patients with AD, five patients with erythrodermic psoriasis vulgaris and 64 healthy individuals. RESULTS: Serum levels of both peptides in AD patients were significantly higher than those in healthy individuals, whereas patients with psoriasis vulgaris did not show any difference from healthy controls. Both sSCF and sKIT levels were positively correlated with the disease severity in AD patients, and decreased after effective treatment with topical corticosteroids. Conclusion Serum levels of sSCF and sKIT may be useful indicators for evaluation of the activity and severity of AD.     

迟发型特应性皮炎的研究进展

特应性皮炎（AD）是一种炎症性皮肤病,与皮肤屏障功能受损密切相关。遗传因素、生活方式、环境因素的暴露都可导致该病的发生。尽管AD常见于婴幼儿,仍有成年后首次出现AD症状,被称为迟发型AD（AOAD）。与儿童期始发的AD相比,AOAD在分型、免疫学机制及与其他疾病的关联方面都存在着显著的差异。皮损分布与婴幼儿期初发的AD相似,但以亚急性和慢性皮炎为主要表现,呈现干燥的、肥厚的皮炎损害,少见渗出。Th1/Th2失衡及抗原提呈细胞的功能亢进是AD发生的免疫学基础。FLG基因突变会影响AD的发生,IL-13升高使FLG存在获得性的表达缺陷仅发生于成年人,提示了AOAD不同于婴幼儿期初发并迁延至成年期的AD。感染、皮肤及肠道菌群改变、吸烟等均可成为诱发AOAD的重要因素,因此在诊断AOAD时询问相关疾病史和吸烟史有助于AOAD的诊断。     

Prevalence of atopic dermatitis in Japanese adults

BACKGROUND: Adult atopic dermatitis (AD) in Japan has become a significant social problem, with as many as one-third of adult patients with severe AD absenting themselves from work or classes due to aggravation of the disease. Reports of such patients have become increasingly common in recent years. Despite the pressing need for epidemiological studies to clarify the prevalence and distribution of AD and to determine its aetiology, no previous research has been carried out on the prevalence of AD within the adult population in Japan. OBJECTIVES: To clarify the prevalence of adult AD in Japan, using the U.K. Working Party's diagnostic criteria. METHODS: The subjects of this study were mostly government officials or their family members visiting the Medical Center of Health Science, Toranomon Hospital in Tokyo for annual health check-ups in the period from September 1997 to August 1998. Questionnaires completed by 10 762 persons (8076 men and 2686 women) aged 30 years or above were analysed. The questionnaire consisted of 14 questions on allergic disease. The U.K. Working Party's diagnostic criteria were used after translation into Japanese. Three types of prevalence were used as indicators of prevalence: point, 1-year and lifetime prevalence. RESULTS: The point prevalence, 1-year prevalence and lifetime prevalence of AD in Japanese adults were 2.9%, 3.0% and 3.3%, respectively. No significant statistical differences were observed between the sexes or among age groups within each sex. The survey indicated that 88.6% of those who had ever had AD were currently affected by active AD, while 93.4% of those who had had at least one episode of AD in the past had experienced an episode over the previous year. CONCLUSIONS: This study gives the first indication of the prevalence of adult AD among the Japanese, based on the U.K. criteria. Both the internal and external validity of this study are believed to be high; it would be safe to conclude that the 1-year prevalence of AD in Japanese adult populations living in urban areas is 3.0%.     

Characteristics of extrinsic vs. intrinsic atopic dermatitis in infancy: correlations with laboratory variables

BACKGROUND: Atopic dermatitis (AD) has been divided into the extrinsic type (ADe) and the intrinsic type (ADi) according to the serum IgE levels and the presence or absence of allergen-specific IgE. Although previous studies have demonstrated differences in the various immunological parameters, the characteristics of AD in infancy have rarely been reported. OBJECTIVES: Our study was performed to analyse the correlations between the laboratory parameters of infantile ADe and ADi. METHODS: We recruited 237 infants with AD and checked the SCORAD index, the number of peripheral blood eosinophils, the serum eosinophil cationic protein (ECP) levels, the total serum IgE levels and the specific serum IgE levels in all the patients. We also checked the serum interleukin (IL)-4 and IL-5 levels in 20 patients with ADe and in 20 with ADi. RESULTS: This study showed many peculiar characteristics of infantile AD. In infancy, ADi was more prevalent than ADe. The eosinophil count, the ECP level and the SCORAD in ADi were lower than in ADe. Furthermore, a group of patients without characteristics of ADi or ADe could be identified. We tentatively classify this group as indeterminate type (ADind) and propose it as a separate entity. The clinical severity was well correlated with the eosinophil count and the serum ECP levels in ADe and ADi. Therefore these two parameters could be used as clinical severity markers in infancy. Infants are more allergic to food, and the variety of specific allergenic responses was connected with clinical severity. A higher eosinophil count, a higher ECP level and a higher detection rate of IL-5 in the peripheral blood of infants with ADe means that eosinophils have a more prominent role in ADe than in ADi. CONCLUSIONS: Infantile AD has many distinctive features in its laboratory variables as compared with AD in other age groups. Clinicians should recognize these facts when they deal with infants with AD, and further studies are warranted on the natural course of infantile AD.     

The characteristics of nocturnal scratching in adults with atopic dermatitis

Patients with atopic dermatitis (AD) are known to suffer from nocturnal itch, and the resultant scratching may worsen the skin lesions. We observed nocturnal scratching for 112 nights in 35 adult patients with AD, using an infrared video camera system. To quantify the amount of scratching, we counted scratching bouts lasting more than 5 s and calculated the duration of all the scratching bouts (total scratching time, TST). The percentage of TST in the total recording time (TST%) was used as an index of nocturnal scratching. Mean +/- SD TST% was 14.3 +/- 13.9 for patients with severe AD, 6.2 +/- 3.7 for those with moderate AD and 0.7 +/- 0.4 for those with mild AD. The higher TST% in the severely affected group was attributed mainly to a longer duration rather than a higher frequency of bouts. Patients scratched more in the first third of the night than in the later two-thirds. Both the group of patients whose disease distribution pattern was generalized and those who showed a head-neck-shoulder type distribution scratched their heads, faces and necks for longer than other parts of the body. Repeated measurement performed on individual subjects resulted in a similar TST% when there was little change in skin lesions. TST% reduced by 15 +/- 21% when the patients showed marked improvement. The measurement of nocturnal scratching helps to evaluate the severity of itch in AD. In addition, the infrared video successfully detected the location and nature of nocturnal scratching in AD.     

213例儿童特应性皮炎临床及病理特点分析

本研究对213例AD儿童患者临床及组织病理学特点进行分析,患儿平均发病年龄为0.88±1.73岁,约85.9%的患者表现为慢性皮炎;约78.9%的患者有个人或家族遗传过敏史。组织病理学示角化过度、微水疱形成、棘层肥厚、海绵水肿、浅层血管周围炎症及嗜酸性粒细胞浸润。     

Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score

It is important to determine the severity of atopic dermatitis (AD) for evaluation of disease improvement after and during therapy. Scoring of the severity of AD is demanded in clinical trials. The European Task Force on Atopic Dermatitis (ETFAD) has developed the SCORAD (SCORing AD) index to create a consensus on assessment methods for AD, so that study results of different trials can be compared. However, modification of the SCORAD index has led on several occasions to wrong and incorrect use of the system. To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded 0-100. The intensity part of the SCORAD index consists of six items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale 0-3. The subjective items include daily pruritus and sleeplessness. Both subjective items can be graded on a 10-cm visual analogue scale. The maximum subjective score is 20. All items should be filled out in the SCORAD evaluation form. The SCORAD index formula is: A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The maximum SCORAD score is 103. Based on training sessions by the ETFAD, the SCORAD index was modified by excluding the subjective symptoms (objective SCORAD). The objective SCORAD consists of just the extent and intensity items, the formula being A/5 + 7B/2. The maximum objective SCORAD score is 83 (plus an additional 10 bonus points). Bonus points are given for severe disfiguring eczema (on face and hands). The three-item severity (TIS) score involves the scoring of erythema (redness), oedema and excoriations (scratches) in one representative lesion, marked as R-O-S. The TIS score corresponds well with the more detailed objective SCORAD and can be used as a prescreening system or as a quick system in studies and is excellent for epidemiological studies.     

Treatment of head and neck dermatitis comparing itraconazole 200 mg and 400 mg daily for 1 week with placebo

BACKGROUND: Head and neck dermatitis (HND) is a variant of atopic dermatitis often seen in young adults. A hypersensitivity to Malassezi antigens is considered to be of pathogenic importance. Previous mostly uncontrolled studies have shown that oral antimycotics might be of use in this condition. OBJECTIVE: To evaluate the efficacy of itraconazole in the treatment of HND in a randomized, double-blind, placebo-controlled trial. PATIENTS: Adult patients with HND were included. Systemic steroids and oral/topical antimycotics were avoided 1 and 2 months prior to the trial. Topical steroids were not allowed in the head and neck area within 2 weeks. Patients in generally good health were included and female patients had to have had a negative urine pregnancy test. The patients signed an informed consent. STUDY DESIGN: The study included a 7-day treatment period and a follow-up period of 105 days. Control visits were carried out on days 3, 7 and 14 and after 15 weeks. METHODS: The SCORAD index (one for the head and neck area and one for the remaining surface area) and global evaluations by patient and investigator were used for clinical evaluation at each visit. Prick tests with Malassezia antigens and Candida albicans antigen were carried out at the start of the trial and included positive and negative controls. The patients were randomized into three groups, which were treated with 400 mg itraconazole daily, 200 mg itraconazole daily or placebo, respectively, for 7 days. RESULTS: The number of patients included was 53: 18 had 200 mg itraconazole daily, 17 had 400 mg itraconazole daily and 18 placebo. At days 7 and 14, significant improvement was seen in the SCORAD of the head and neck area for the groups given 400 mg itraconazole daily (P = 0.0385 and P = 0.0134), and 200 mg daily (P = 0.0104 and P = 0.0006). Patients in the placebo group improved slightly (P = 0.0785). At day 14, comparison of improvement of SCORAD of the head and neck area between all three groups showed a significant difference in favour of the 200 mg itraconazole group compared to the placebo group (P = 0.0318). The prick test was positive for Pityrosporum ovale in 37% and negative for C. albicans in all patients. CONCLUSIONS: One week of treatment with 200 or 400 mg itraconazole as a single treatment has a significant effect on the head and neck area. Compared to placebo there was a significant improvement in SCORAD of the head and neck area in favour of the 200 mg itraconazole group after 14 days. The important observation seems to be that antifungal systemic treatment has a significant SCORAD reduction of atopic dermatitis, irrespective of the presence of allergy.     

Factors influencing the occurrence of hand eczema in adults with a history of atopic dermatitis in childhood

A series of 955 persons aged 24-44 years, with atopic dermatitis in childhood, were interviewed in order to identify factors which increase the risk of developing hand eczema in adult life, or aggravate already existing hand eczema. Endogenous (constitutional) factors were in general of greater importance than exogenous factors, viz. chemicals, water, soil and wear (friction). Eczematous involvement of the hands in childhood was of predominant importance. In individuals without such involvement, severe (widespread) dermatitis in childhood was a dominant factor. Other factors, each of them significantly more important than the exogenous ones, were persistent eczema on other parts of the body and dry/itchy skin. The factors female sex, family history of atopic dermatitis and simultaneous bronchial asthma/allergic rhinitis were associated with increased risk of developing hand eczema in adult life, but were of limited importance compared with the other endogenous and the exogenous factors.     

Biologics in atopic dermatitis

Atopic dermatitis (AD) accounts for a significant share of chronic inflammatory skin disorders. There is a niche for the development of biologics to treat recalcitrant autoinflammatory stage AD seen mostly in adults. The heterogeneity of patient response to various existing biotherapies points to involvement of various immune responses and suggests that therapies must preferably target early development of allergen‐specific B‐ and T‐cell clones. In addition to immune targets, tissue factors that help restore the normal epidermal environment constitute interesting therapeutic tools. Several approaches are needed to find the appropriate targets in a field where so many have been investigated without definitive proof of concept for human systemic therapy. The keys to success are probably (1) to influence the inflammatory skin pattern towards less pruritogenic effects, requiring us to better understand pruritogenic inflammation and (2) to limit the amplification loop of disease by attacking abnormal regulatory mechanisms which perpetuate skin autoinflammation.     

Phenotypes of atopic dermatitis

Atopic dermatitis (AD) is a common disease affecting both children and adults. AD develops from a complex interplay between environmental, genetic, immunologic and biochemical factors. Genetic factors predispose atopic subjects to mount exaggerated Th2 responses and to a poorly efficient epidermal barrier, which may be sufficient to initiate inflammation in the skin and may favor allergic sensitization. Thus AD can present with different clinical pheno‐types. AD is classically distinguished into an intrinsic and extrinsic form, which are clinically identical but the former lacks high level specific IgE and is not associated with respiratory atopy. Although in many cases AD presents with monotonous eczematous lesions on the face, neck and skin folds, it may also present with other features. Very common is nummular eczema, which in many instances may be the dominant expression of AD. In other patients, AD affects limited areas (periorificial eczema, nipple eczema, cheilitis, hand eczema) or its main presentation is with excoriated papules and nodules (atopic prurigo). In conclusion, AD is a multifaceted disease affecting patients with epidermal barrier dysfunction and dry and sensitive skin. The recognition of the less common AD phenotypes is essential for proper patient management.