Efficacy of Dupilumab in two patients with severe and recalcitrant atopic dermatitis previously treated with extracorporeal photopheresis

Atopic dermatitis (AD) is a complex disease and can often be a clinical challenge for dermatologists. When standard immunosuppressive therapies fail, extracorporeal phototherapy (ECP) can be considered as a therapeutic option. In recent years, better understanding of the pathogenesis of AD allowed to improve treatment strategies with many emerging therapeutic options. Currently, Dupilumab, a monoclonal antibody that selectively inhibits IL‐4 and IL‐13, is the only biological drug authorized for the treatment of severe adult atopic dermatitis, refractory to traditional firstline and secondline therapies. ECP, compared to biological therapy, is associated with some disadvantages: it is costly and time‐consuming for patients and personnel to administer. Moreover, it should be noted that the completion of the entire procedure takes about 3 hr and must be done in a hospital, while the administration of Dupilumab can be carried out by patients themselves at home. For these reasons and on the basis of our experience, it would be necessary to evaluate whether all patients with refractory atopic dermatitis in treatment with ECP with unsatisfactory clinical response should be switched to recent available target therapies.     

Efficacy and safety of combination ointment "fluticasone propionate 0.005% plus mupirocin 2.0%" for the treatment of atopic dermatitis with clinical suspicion of secondary bacterial infection: an open label uncontrolled study

BACKGROUND: The skin of patients with atopic dermatitis is colonized with Staphylococcus aureus. Reduction of bacterial colonization has been reported to be effective in the treatment of atopic dermatitis. AIM: To assess the efficacy and safety of a combination of fluticasone propionate 0.005% and mupirocin 2.0% ointment twice daily for 2 weeks in patients with atopic dermatitis clinically suspected of secondary bacterial infection. METHODS: An open-label, non-randomized study of 122 patients (64 males and 58 females) from 20 centers was conducted. Atopic dermatitis was diagnosed by clinical assessment and scoring was done on the visual analogue scale (VAS). Clinical evaluation of the lesions was done on day 1 (baseline), day 8 and on day 15 of study visits. RESULTS: At baseline, many patients had moderate itching (41.8%), moderate dryness (41.8%) and mild weeping lesions (49.2%). The baseline proportions of the clinicians' global impressions (CGI) scale for mild, moderate and severe atopic dermatitis lesions were 19.7%, 55.7% and 12.2% respectively. At the end of the treatment period, 67.2% patients had mild disease, whereas only 9% and 0.8% patients had moderate and severe disease respectively. At baseline, only 33.65% patients were comfortable with the existing lesions when assessed on visual analog scale (VAS). However, after the treatment, this proportion increased to 51.77% and 78.60% patients on day 8 and on day 15 respectively. CONCLUSION: Twice daily topical application of a fluticasone propionate 0.005% and mupirocin 2.0% ointment is an effective and safe therapeutic regimen in atopic dermatitis.     

Specific IgE and skin tests to house dust and storage mites and eosinophil cationic protein in scabies

Background In addition to the infestation with scabies mites also allergic IgE mediated mechanisms play a role in the pathogenesis of scabies. Aim The aim of this study was to answer the question whether specific IgE mediated reactions to house dust and storage mites can be found and whether eosinophils are involved in the pathogenesis of scabies. Material 44 scabies patients (12 children. 32 adults) were classified according to the extent of skin involvement as mild, moderate and severe. Age- and sex-matched healthy controls and patients with atopic dermatitis were studied for comparative purposes. Methods Total and specific IgE to Dermatophagoides pteronyssinus, D. farinae, Acartis siro and Pityrosporon ovale were tested by CAP-FEIA (Pharmacia. Sweden) before and 6 weeks after treatment and prick tests were performed with the same allergens. The number of eosinophils in the peripheral blood and tissue specimens was counted and the eosinophil cationic protein (ECP) was determined by CAP-FEIA in serum before and 6 weeks after therapy. Results The total IgE was increased in 86% of patients. It was correlated with the extent of skin involvement (p < 0.05) and was significantly less increased 6 weeks after treatment (p < 0.115). Specific IgE to house dust and storage mites was increased up to 48% in the CAP-EEIA and up to 61% in the prick test, all together significantly higher than in controls and in comparable frequencies with atopic dermatitis. Pityrosporon ovate IgE was within normal ranges. Die ECP levels were increased in 89% of patients and correlated only in mild versus moderate or severe extent of the disease. 6 weeks after treatment, however, they were significantly less increased (p < 1.01). In addition. ECP levels were correlated with the IgE levels in scabies (C = 0.88). The number of eosinophils in the peripheral blood was increased in 64% of cases and in tissue specimens in 84% of cases studied. In principle, the extent of skin lesions was milder and the frequencies of specific IgE in the CAP- and prick test as well as the levels of total IgE (p < 0.01) and ECP (only in the tendency) were lower in children than in adults. Discussion The frequencies in the total and specific IgE to house dust and storage mites are comparable with those in atopic dermatitis. The question remains open, whether this is due to cross reactivity with scabies mites or whether this suggests an enhanced susceptibility to generalized scabies eruption. The increase in the ECP and its correlation to IgE, its decline after treatment (p < 0.05) and the occurrence of eosinophils in the peripheral blood and in inflammatory infiltrates of the skin suggest the involvement of eosinophils in the pathogenesis of scabies as an ectoparasitic IgE mediated disease.     

An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids. However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy. The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis.     

Eosinophil involvement in atopic dermatitis as reflected by elevated serum levels of eosinophil cationic protein.

Eosinophil cationic protein (ECP), one of the eosinophil granule proteins, is released during allergic reactions. We investigated the possibility of correlations among the serum levels of ECP, clinical activity, and eosinophil number in patients with atopic dermatitis (AD). Forty-four patients with AD and 25 normal, non-atopic subjects were studied. ECP was quantitated by a double antibody radioimmunoassay. The levels of serum ECP correlate with the grading of severity of clinical evaluations in AD. The patients with severe and moderate AD had significantly higher ECP concentrations than normal controls (p less than 0.001); mild AD had levels identical with those of control groups. A positive correlation was observed between the number of peripheral blood eosinophils and serum ECP levels in the severe cases (r = 0.67, p less than 0.05). Furthermore, these ECP levels significantly decreased in response to either improvement of clinical severity of AD or decreased numbers of blood hypodense eosinophils in anti-allergic drug-treated patients. No coefficient of correlation was observed between serum ECP and IgE levels. These findings indicate that eosinophils may release their granular contents, including ECP, into the peripheral circulation and/or inflammatory skin lesions and subsequently provoke a clinical exacerbation by stimulating allergic reactions.     

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.     

Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis

BACKGROUND: Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies. OBJECTIVES: We therefore performed a randomized controlled study of house dust mite control in patients with this disease. METHODS: Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 microg g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year. RESULTS: At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups. CONCLUSIONS: For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.     

Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey

Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self‐reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity‐score matched with non‐atopic dermatitis controls (1:2 ratio) on demographic variables. Patient‐reported outcome data on comorbidities, mood and sleep disorders, health‐related quality of life, work productivity and activity impairment, and health‐care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as “moderate/severe” and 348 (54.5%) as “mild”. The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health‐related quality of life, higher overall work and activity impairment, and higher health‐care resource utilization (all P < 0.001). Self‐rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management.     

【开放获取】度普利尤单抗治疗特应性皮炎专家共识

【摘要】 特应性皮炎是一种常见的慢性炎症性皮肤病,以湿疹样皮疹和剧烈瘙痒为主要表现,可严重影响患者生活质量。中重度特应性皮炎往往需要系统治疗,传统的系统治疗对部分患者效果不佳或不能耐受。近年来,生物制剂开始用于临床治疗特应性皮炎,其中白细胞介素4受体拮抗剂度普利尤单抗已经在我国上市。中华医学会皮肤性病学分会特应性皮炎研究中心、中华医学会皮肤性病学分会儿童学组组织本领域部分专家讨论度普利尤单抗在中重度特应性皮炎治疗中的应用,并形成共识,希望本共识能为我国皮肤科医生临床应用度普利尤单抗治疗特应性皮炎提供参考。     

Treatment of severe atopic dermatitis with extracorporeal photopheresis

Extracorporeal photopheresis using UVA irradiation of enriched lymphocytes in the presence of 8-methoxypsoralen (8-MOP) as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. We report on the first three patients subjected to extracorporeal photopheresis for severe atopic dermatitis. All patients had a lifelong history of atopic skin inflammation, and their disease had finally become resistant to well-established therapeutic regimes. Extracorporeal photopheresis resulted in a marked clinical improvement in the skin lesions of all patients. The decrease in cutaneous inflammatory activity became evident by the end of the second photopheresis cycle. In two patients skin lesions had virtually disappeared after the fifth treatment cycle, while in the third patient a lasting and substantial improvement in pruritus and erythema was achieved. Clinical remission was stable under maintenance therapy with prolonged intervals between photopheresis sessions. Therapeutic efficacy was reflected by a marked reduction in IgE serum levels in all three patients, while serum concentration of IgG, IgM and IgA as well as the profile of circulating lymphocytes remained essentially unchanged. No clinical signs of immunosuppression or other severe adverse events became evident. Collectively, our preliminary results indicate that extracorporeal photopheresis may interfere with the pathomechanisms leading to atopic dermatitis and therefore should be considered as a treatment modality for severe forms of this recalcitrant disorder.     

Soluble E-selectin in sera of patients with atopic dermatitis and psoriasis—correlation with disease activity

Summary E-selectin endothelial leucocyte adhesion molecule-1 is expressed on endothelial cells in distinct inflammatory skin diseases. E-selectin mediates the adhesion between activated endothelium and different inflammatory cells. To evaluate soluble E-selectin as a marker of disease activity in patients with atopic dermatitis and psoriasis, the concentration of soluble E-selectin, determined by ELISA, was studied in sera of patients before and after treatment and compared with normal non-atopic controls. The disease severity was established using clinical scoring systems. Levels of soluble E-selectin were significantly elevated in sera of patients with atopic dermatitis and psoriasis (as compared with controls). Clinical improvement, after treatment, in patients with atopic dermatitis, but not in psoriasis, was associated with a significant decrease in serum levels of soluble E-selectin. There was a significant correlation of soluble E-selectin and disease activity in patients with atopic dermatitis. These data indicate that soluble E-selectin is another parameter to evaluate the inflammatory response in atopic dermatitis and psoriasis. Determination of soluble E-selectin may be a useful measure of disease activity in atopic dermatitis.     

Dupilumab treatment improves quality of life in adult patients with moderate‐to‐severe atopic dermatitis: results from a randomized,placebo‐controlled clinical trial

Atopic dermatitis is a skin disease, commonly known as eczema. It affects up to 1 in 10 adults. Atopic dermatitis is usually very itchy, causing people to wake up at night, and feel “low”. This state of general discomfort is known as reduced quality of life. Dupilumab is a new treatment approved in the U.S.A. for adults with moderate‐to‐severe atopic dermatitis. The treatment blocks some of the mechanisms involved in the disease. In a clinical trial conducted in Europe, researchers observed 109 patients with moderate‐to‐severe atopic dermatitis. The patients received dupilumab over 12 weeks. They found that the treatment improved the eczema and its symptoms, such as itch. The researchers also studied how the treatment affected quality of life in 64 out of 109 patients in the study. These patients had answered a set of questions that measures how atopic dermatitis affects their quality of life (Quality of Life Index for atopic dermatitis [QoLIAD]). Thirty‐two patients received dupilumab 300 mg weekly, by injection under the skin, and 32 received placebo. About 6 out of 10 patients treated with dupilumab had better quality of life over the 12 weeks, whereas only about 1 in 10 placebo‐treated patients improved. The researchers also found a relatively strong link between improvements with dupilumab in QoLIAD score and improvements in the eczema and symptoms. Dupilumab was well‐tolerated by the patients. The authors conclude that dupilumab, a new breakthrough treatment for atopic dermatitis, improves eczema and its symptoms, and in turn, the patients’ quality of life.     

Common burden of chronic skin diseases? Contributors to psychological distress in adults with psoriasis and atopic dermatitis

BACKGROUND: Chronic skin diseases, such as atopic dermatitis and psoriasis, are known to affect quality of life by heightening psychological distress. Knowledge about factors contributing to psychological distress is essential for supporting physicians in diagnostic and multidisciplinary treatment options for patients psychologically at risk. OBJECTIVES: To examine whether generic physical, psychological and social factors relevant to patients with chronic diseases might contribute to psychological distress in adults with psoriasis and atopic dermatitis. METHODS: Self-report data on clinical skin status, physical symptoms of itching and fatigue, impact of the disease on daily life, illness cognitions and social support were collected from 128 patients with psoriasis and 120 patients with atopic dermatitis (aged over 16 years). RESULTS: For patients with either skin disease, clinical status and physical symptoms of itching scarcely affected psychological distress. Instead, higher levels of fatigue, perceived helplessness and less social support best predicted psychological distress in patients with both skin diseases in multiple regression analyses. CONCLUSIONS: Results demonstrate that generic physical, psychological and social aspects play a role in chronic skin diseases and suggest that multidisciplinary care for patients with psoriasis and atopic dermatitis can be greatly improved by integrating common screening and treatment components for chronic diseases.     

Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults

Atopic dermatitis, also known simply as eczema, is a long-term skin condition that causes an itchy rash. Scratching can cause skin to weep, crust, become infected and become thicker. 16.5 million adults in the USA suffer from atopic dermatitis, with 6.6 million reporting moderate to severe symptoms. Those with more severe disease have been found to have worse quality of life and increased risk of depression and anxiety. This US-based study looked at 2893 adults to see if having atopic dermatitis, and how severe it is, affects the likelihood of also having anxiety or depression. Information was collected by sending out a survey. Modified UK diagnostic criteria were used to screen for patients with atopic dermatitis. Disease severity was self-reported by patients using tools such as the Patient-Orientated Eczema Measure and Dermatology Life Quality Index. The Hospital Anxiety and Depression Scale (HADS) was used for measuring anxiety and depression. 602 adults had atopic dermatitis. They had higher HADS scores (meaning higher levels of anxiety and depression) than the 2291 adults without atopic dermatitis. There were more adults with atopic dermatitis who also had a formal diagnosis of anxiety or depression than those without atopic dermatitis. However, many atopic dermatitis patients with high HADS scores had no formal diagnosis of anxiety or depression. Furthermore, patients with more severe atopic dermatitis had higher HADS scores than those with milder disease. The conclusion is that atopic dermatitis increases the likelihood of having anxiety and depression, especially if one has severe disease. This may go undiagnosed.     

The risk of cancer among patients previously hospitalized for atopic dermatitis

In treatment of severe atopic dermatitis, drugs with carcinogenic potentials are used to manage the disease. We therefore analyzed whether patients having severe atopic eczema had an increased cancer risk. The study population included all individuals hospitalized in Denmark with a primary diagnosis of atopic dermatitis during 1977-1996. Follow-up was conducted in 1996 in the Danish Cancer Register. A total of 6275 persons were included. Among 2030 adult patients, an increased risk of cancer was observed, standard morbidity ratio (SMR)=1.5 (95% CI: 1.2-1.9). Half the excess cases of cancer was keratinocyte carcinomas of the skin diagnosed within the first 9 y of follow-up, SMR=2.4 (95% CI: 1.4-3.9). For men, SMR=2.7 (95%CI: 1.2-5.4). In conclusion, earlier hospitalized adult atopic dermatitis patients had an increased risk of cancer. Half the excess cases of cancer were keratinocyte carcinomas. This may be a result of a detection bias or due to the carcinogenic potentials of some of the therapies of severe atopic dermatitis.     

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.     

Atopic dermatitis is associated with a decrement in health-related quality of life

BACKGROUND: Although atopic dermatitis is a chronic skin disease that can have a major impact on a patient's life, the burden of illness associated with this condition has not been well characterized. OBJECTIVE: To determine the health-related quality of life (HRQL) of patients with atopic dermatitis by disease severity and to compare it with that of the general public and of patients suffering from other chronic illnesses or skin disorders. METHODS: Two hundred and thirty-nine atopic dermatitis patients aged 4-70 years completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36) and the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index. These HRQL scores were compared by self-reported patient disease severity ratings. Health-related quality of life scores were compared with those of the general population and those of patients with other chronic conditions (clinical depression, hypertension, type 2 diabetes) or skin disease (psoriasis). Dermatology Life Quality Index scores were also compared with those of other skin diseases (such as psoriasis, Darier's disease, and Hailey-Hailey disease). RESULTS: Patients with atopic dermatitis had inferior scores on the SF-36 vitality, social functioning, and mental health subscales compared with individuals in the general population. In seven of eight subscales, individuals reporting more severe disease had inferior DLQI and SF-36 scores. Patients with atopic dermatitis had inferior mental health scores compared with those with diabetes or hypertension, and inferior social functioning scores compared with patients with hypertension. When compared with a psoriasis cohort, patients with atopic dermatitis had inferior scores in the role-physical, vitality, social functioning, role-emotional, and mental health SF-36 domains. Patients with atopic dermatitis had similar DLQI scores to patients with other chronic dermatologic diseases. CONCLUSIONS: These results demonstrate that atopic dermatitis has an impact on HRQL, particularly in social functioning and psychological wellbeing. Patient-assessed severity of atopic dermatitis correlates with HRQL decrements, indicating greater HRQL impact with greater disease severity. Atopic dermatitis has as large an impact on HRQL as several chronic conditions and other dermatologic conditions.     

Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptor with the clinical activity of atopic dermatitis.

To evaluate the correlation with the clinical activity of atopic dermatitis (AD) we investigated prospectively cellular and serological parameters such as eosinophils, eosinophil cationic protein (ECP), soluble IL-2 receptor (sIL-2R), soluble CD23 (sCD23) and lactate dehydrogenase (LDH) in peripheral blood of 37 AD patients on admission to and discharge from the Department of Dermatology at the University Hospital in Zurich. On admission the actual clinical skin condition as measured by the skin intensity score (SIS) was significantly correlated with eosinophils (p less than 0.005), ECP (p less than 0.05) and sIL-2R (p less than 0.001). During the observation period a significant improvement in the clinical status as measured by the SIS was observed in all AD patients (p less than 0.001). A significant decrease in sIL-2R (p less than 0.005), which was most pronounced in the group of AD patients receiving systemic steroids, together with a decrease in eosinophils and ECP but not in sCD23 and LDH could be demonstrated between admission and discharge. In addition, a slight but significant increase in peripheral blood lymphocytes (p less than 0.005) and monocytes (p less than 0.01) was noted. Comparing the 'extrinsic' (n = 32) and the 'intrinsic' (n = 5) types of AD no significant differences with regard to the above mentioned parameters were found. Our data indicate that cellular and serological parameters such as eosinophils, ECP and sIL-2R reflect the clinical activity of AD and may therefore give further insights into the pathogenesis of this disease.     

Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis.

Atopic dermatitis, a common, chronic, inflammatory skin disease that occurs with increasing prevalence, is characterized by hyperactivated cytokines of helper T cell subset 2 and is frequently associated with staphylococcal infection. An experimental animal model of atopic dermatitis induced by transgenically introduced cytokine is not available. We generated a transgenic mouse line expressing epidermal interleukin-4, a critical cytokine of helper T cell subset 2. Here we show that transgenic mice spontaneously developed a pruritic inflammatory skin disease reproducing all key features of human atopic dermatitis, including xerosis, conjunctivitis, inflammatory skin lesions, Staphylococcus aureus infection, histopathology of chronic dermatitis with T cell, mast cell, macrophage-like mononuclear cell, and eosinophil infiltration, and elevation of total serum IgE and IgG1. The onset and early progression of skin disease coincided with increased total serum IgE and IgG1. The mouse disease occurred at a 43% annual incidence rate and primarily affected the poorly haired skin: ear (100%), neck (65%), eye (53%), face (29%), tail (12%), leg (12%), and torso (6%). As a group the affected transgenic mice manifested with a skin disorder that fulfilled the clinical diagnostic criteria established for atopic dermatitis in human patients. Pending further characterization to authenticate it as a model of atopic dermatitis, this experimental animal model of pruritic inflammatory skin disease may facilitate investigations for the roles of interleukin-4 in cutaneous inflammation and skin infection in human patients.