The caseload, assessment and treatment of atopic dermatitis: a survey of Australian dermatologists

In early 1995 we surveyed all 250 practicing Australian members of the Australasian College of Dermatologists by a mail-out questionnaire to determine information, such as the caseload imposed by atopic dermatitis, the severity of cases seen by dermatologists, current treatment and dermatologists' satisfaction with treatment. One hundred and forty-nine responses were received. Fifty per cent of patients with atopic dermatitis seen by dermatologists were younger than 10 years, 18% were 10-16 years, and 52% were older than 16 years. Disease was considered to be severe in 18% of patients, moderate in 41% and mild in 41%. Emollients and topical corticosteroids were the most commonly used treatments but there was wide variation in other treatments used by individual dermatologists. Only 10% of respondents were very satisfied with existing treatments for severe atopic dermatitis; 20% of patients with severe disease were considered as refractory or non-responsive. New therapies such as cyclosporin have the potential to improve existing standards of care.     

Familiar and environmental factors influencing atopic dermatitis in the childhood

BACKGROUND: The increase in the incidence of atopic dermatitis (AD) in developed countries has been related to familiar and environmental factors. This survey was undertaken to investigate the family background, birthweight and the home environment of children suffering from AD in order to point out the possible factors that provoke the development of the disease. METHODS: The study uses data collected by means of self-administered questionnaires and discusses 461 cases of children (age 0-12) with active skin signs of AD. The control group comprised of 343 children (age 0-12) with no skin signs or positive lifetime history of AD. Associations between familiar and various home environmental factors and the risk of AD were calculated by means of odds ratios. RESULTS: There were statistically significant positive associations between atopic eczema symptoms and higher birthweight, small households, wall-to-wall carpets, as well as indoor-kept pets. Day-nursery attendance, heating system and indoor smoking, however, did not significantly alter the risk of the disease. CONCLUSIONS: Because of the limitations of a retrospective questionnaire study, further research is needed to confirm these associations and clarify whether they are causative.     

Itch and atopic dermatitis: an overview

Itching is the hallmark of atopic dermatitis, and a vicious itch-scratch circle is easily established. Itching and scratching are important factors in the maintenance of symptoms and can have a significant impact on the sufferer's quality of life. The pathophysiology of itch in atopic dermatitis is still not understood. Unlike in urticaria, histamine is not considered to be a major pruritogen in atopic dermatitis. In fact, the peripheral pruritogens and their cellular origin(s) still remain to be identified in this disease. Various treatments are used to relieve the skin inflammation, itching, and scratching in patients with atopic dermatitis, but no specific antipruritic therapy is available. However, several nonspecific therapies can effectively break the vicious itch-scratch circle. The use of topical corticosteroids and emollients and the elimination of individual trigger factors are still first-line measures.     

Azathioprine in severe adult atopic dermatitis: a double-blind,placebo-controlled,crossover trial

BACKGROUND: There is a limited range of treatments for severe atopic dermatitis (AD). Azathioprine has often been used but there has been no randomized controlled trial of this drug to confirm its efficacy in AD. OBJECTIVES: To establish or refute the efficacy of azathioprine in severe AD. To investigate the safety and tolerability of azathioprine in this patient population. METHODS: We performed a double-blind, randomized, placebo-controlled, crossover trial of azathioprine in adult patients with severe AD. Each treatment period was of 3 months' duration. Treatments were azathioprine 2.5 mg kg(-1) day(-1) and matched placebo. Disease activity was monitored using the SASSAD sign score. In addition, severity of pruritus, sleep disturbance and disruption of work/daytime activity were monitored using visual analogue scales. Adverse events were recorded and haematological and biochemical monitoring was performed. RESULTS: Thirty-seven subjects were enrolled, mean age 38 years (range 17-73). Sixteen were withdrawn, 12 during azathioprine treatment and four during placebo treatment. The SASSAD score fell by 26% during treatment with azathioprine vs. 3% on placebo (P < 0.01). Pruritus, sleep disturbance and disruption of work/daytime activity all improved significantly on active treatment but not on placebo. The difference in mean improvement between azathioprine and placebo was significant for disruption of work/daytime activity (P < 0.02) but not for pruritus or sleep disturbance. Gastrointestinal disturbances were reported by 14 patients during azathioprine treatment and four were withdrawn as a result of severe nausea and vomiting. Leukopenia was observed in two patients and deranged liver enzymes in eight during treatment with azathioprine. CONCLUSIONS: Azathioprine is an effective and useful drug in severe AD although it is not always well-tolerated. Monitoring of the full blood count and liver enzymes is advisable during treatment.     

Systemic therapy of paediatric atopic dermatitis: an update

Topical therapies are the mainstay in the treatment of atopic dermatitis, and are effective in the majority of patients with mild and localized disease. In patients with widespread or recalcitrant moderate to severe dermatitis, systemic therapies may be required. The frequently used systemic therapies are immunosuppressants, immune response modifiers, anti-inflammatories, antihistamines, and antibiotics. In this article, the indications and scientific support for the use of these medications is reviewed.     

Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.     

A new instrument for assessing quality of life in atopic dermatitis: international development of the Quality of Life Index for Atopic Dermatitis (QoLIAD)

BACKGROUND: Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that can have a considerable impact on those affected. There are a number of instruments available to measure outcome in dermatological conditions but none have been developed specifically for AD. In addition, most measure symptoms and/or daily functioning, which are potential influences on quality of life (QoL) rather than assessments of the construct itself. OBJECTIVES: The aim of the current study was to develop a new instrument specifically designed to measure QoL in adults with AD-the Quality of Life Index for Atopic Dermatitis (QoLIAD). METHODS: The instrument was developed based on the needs-based model of QoL and was produced in several different countries simultaneously. Its content was derived from 65 in-depth interviews with relevant patients in the U.K., Italy and the Netherlands. The initial version of the measure was produced in U.K. English and translations were produced for the Netherlands, Italy, Germany, France and the U.S.A. using a dual translation panel methodology. A Spanish version was developed using the same adaptation process after the instrument was finalized. Field-test interviews were conducted with approximately 20 patients in each country to assess face and content validity. The instrument [in addition to the Dermatology Life Quality Index (DLQI) and the Psychological General Well-Being Schedule (PGWB)] was then administered to up to 300 AD patients in each country at two time points to finalize the instrument and test its psychometric properties. RESULTS: The initial version of the QoLIAD had 56 items that reflected the areas of need fulfillment identified in the qualitative interviews as having been affected by AD: mental and emotional stimulation, physical and emotional stability, security, sharing and belonging, self-esteem, personal development and fulfillment. Comments from patients in field-test interviews resulted in the removal of 14 items, to leave a 42-item instrument that was considered relevant and acceptable. The number of patients participating in the survey were 286 in the U.K., 46 in the Netherlands, 213 in France, 187 in Germany, 178 in the U.S.A. and 83 in Spain. Application of the Rasch model to these data identified the final 25-item QoLIAD. Unidimensionality was confirmed, with deviation of the total scale from the Rasch model evident at a single time point in one country only (the U.K.). All language versions, with the exception of the Dutch measure, had test-retest reliability coefficients in excess of 0.85. The test-retest in the Netherlands was 0.80. However, this country had the smallest sample size and the corresponding reliability for the DLQI was only 0.40. The QoLIAD had adequate internal consistency and the initial indications of construct validity were good. The levels of association with the DLQI indicated that the two instruments measure related but distinct constructs. CONCLUSIONS: The QoLIAD is a practical, reliable, valid and culturally applicable instrument for measuring the impact of AD and its treatment on QoL in clinical trials or in routine clinical practice.     

Hand dermatitis among university hospital nursing staff with or without atopic eczema: assessment of risk factors

Background. Nurses are prone to develop hand dermatitis. Although an atopic constitution has been identified as a genetic risk factor, the behavioural risk factors associated with hand dermatitis in wet work conditions have not been fully explored. Objectives. This study aimed to clarify the impact of atopic eczema (fulfilling the diagnostic criteria during the past 1 year) on the occurrence of hand dermatitis and to identify the behavioural risk factors among non‐atopic nurses with hand dermatitis. Methods. From August 2007 to July 2009, nurses from Kaohsiung Medical University Hospital were recruited. The associations between different risk factors and hand dermatitis were documented. In addition, the behavioural risk factors among non‐atopic nurses were evaluated via observational study. Results. One thousand one hundred and thirty‐two nurses participated in the first part of the study, which revealed that individuals with atopic eczema had a 3.76‐fold increased risk for hand dermatitis. However, among 248 nurses with hand dermatitis, only 43 had atopic eczema. The observational study performed on 140 non‐atopic nurses identified frequency of hand washing as the behavioural risk factor associated with hand dermatitis. Conclusions. Although atopic eczema is the major risk factor for hand dermatitis, those with atopic eczema constitute only 17% of nurses with hand dermatitis. Decreasing hand washing frequency is the most effective strategy to reduce the occurrence of hand dermatitis among non‐atopic nurses.     

Comparative trial of moisturizer containing licochalcone A vs. hydrocortisone lotion in the treatment of childhood atopic dermatitis: a pilot study

Background Although moisturizer usage has been considered a mainstay of treatment for atopic dermatitis (AD) patients, few clinical studies have been investigated. Recently, moisturizers containing non‐steroidal anti‐inflammatory agents, such as licochalcone A (LA) and vitamin B₁₂ are of emerging interest. Objective To compare the effectiveness of moisturizer containing LA with hydrocortisone (HC) lotion in treatment of childhood AD. Methods The randomized, controlled, investigator‐blinded 6‐week study was conducted. Patients were administered with twice‐daily application of LA lotion on one side of the body and HC lotion on the opposite side. The clinical outcome was assessed by the scoring of atopic dermatitis (SCORAD) index. The relapse rate was comparatively analysed by survival analysis. Results From 30 patients enrolled, 26 patients completed the protocol. The mean age of the children was 5.8 years. The average baseline SCORAD score is about 28 on both sides. The response rates of both agents were equal to 73.33%. There is no statistical significant group difference in reduction of SCORAD score. Although we observed more rapid resolution of oedema and erythema in areas treated with HC lotion, both agents exhibited no significant difference. The relapse rate of HC group was higher than in LA group; however, there was no significant difference. No side‐effect was observed from both agents. Conclusion The effectiveness of LA lotion is equal to that of HC lotion. It was suggested that moisturizer containing LA could be used both for treatment of acute and maintenance phase in mild‐to‐moderate childhood AD.     

Prognosis and prognostic factors in adult patients with atopic dermatitis: a long-term follow-up questionnaire study

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease. Several investigations concerning the long-term prognosis of AD among children and teenagers have been performed but there are only few data among adults. OBJECTIVES: To investigate the prognosis and prognostic factors in adult patients with AD by a long-term follow-up (25-38 years). The prognostic factors were defined as those factors of importance for the persistence of AD. PATIENTS AND METHODS: A follow-up questionnaire was sent in November/December 1998 to 922 AD patients examined in our outpatient clinic between 1960 and 1973 among 1366 registered patients with AD. The patients were aged 20 years or older when they visited the clinic and 45 years or older when they answered the follow-up questionnaire. RESULTS: The response rate was 90.4%. The age range at the time of follow-up was 45-86 years (mean 55 years). Of the 833 patients who responded, 59% reported AD at some time during the last 12 months, which we defined as persistent AD. The mean value of clearance rate per person-years was 18%. One of the most important factors associated with persistence of AD was a head and neck dermatitis with or without other AD locations at the time of examination according to the old patient records. CONCLUSIONS: This study showed that the majority of adults with AD still had AD when they became older. This applies particularly if negative prognostic factors existed.     

Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. A randomized controlled trial

BACKGROUND: Previous studies suggested that early intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a relapse of atopic dermatitis (AD) following remission may prevent the occurrence of more severe flares and therefore reduce corticosteroid exposure in the long term. However, this possibility was not rigorously evaluated. OBJECTIVES: To evaluate the effectiveness of pimecrolimus cream 1% for the prevention of flare progression in adults with AD. METHODS: A 26-week randomized controlled study was conducted in 543 patients aged>or=18 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n=277) or matching vehicle cream (n=266). Twice-daily treatment with study medication was started at the onset of the first signs and/or symptoms of a relapse. If disease worsened, despite the application of study medication for at least 3 days, treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy endpoint was the number of days without TCS use for disease worsening. RESULTS: The mean number of TCS-free days was significantly higher (P<0.001) in the pimecrolimus cream 1% group (152 days) than in the vehicle cream group (138.7 days). In comparison with vehicle cream, pimecrolimus cream 1% reduced the mean number of flares requiring TCS use from 1.39 to 0.97 (P=0.0014). Patients on pimecrolimus cream 1% made 30% fewer unscheduled visits (156) than patients on vehicle cream (223). CONCLUSIONS: In adults with a history of mild or moderate AD but free of active skin lesions, intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a subsequent recurrence reduces the number of flares requiring TCS use and decreases the number of disease-related office visits.     

The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study

BACKGROUND: While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. OBJECTIVES: To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. METHODS: Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. RESULTS: CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. CONCLUSIONS: Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.     

Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis

BACKGROUND: The skin of up to 100% of patients with atopic dermatitis (AD) is colonized with Staphylococcus aureus. Of all S. aureus strains isolated from lesional skin, up to 65% have been shown to produce exotoxins with superantigenic properties. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. These studies did not consider the anterior nares as a reservoir of S. aureus, or the possibility of transmission between patients and their contacts. Moreover, adult patients have not so far been investigated. OBJECTIVES: To investigate the colonizing features of S. aureus in adults with AD and in their contacts, and the effect of an antimicrobial treatment of the patients and their partners. METHODS: Swabs were taken from the skin and anterior nares of 66 adults with AD. S. aureus strains were screened for the production of exotoxins in 32 patients. Ten patients (two with toxigenic strains, eight with non-toxigenic strains) were treated orally with cefalexin, chlorhexidine ointment was applied to the skin, and the anterior nares were treated with mupirocin ointment. A bath containing potassium permanganate was taken daily. In addition, their partners were treated topically. RESULTS: Sixty-two of 66 patients (94%) were carriers of S. aureus, and mostly harboured the bacteria on both skin and anterior nares. Ten of 32 (31%) patients were colonized with toxigenic strains. The Severity Scoring in AD (SCORAD) score decreased in nine of 10 patients who received antimicrobial treatment (P < 0.001), and this effect was more pronounced in patients with a baseline SCORAD > 50. CONCLUSIONS: S. aureus may play an important role as an aggravating factor in adults with AD, as antimicrobial treatment leads to a significant improvement of AD in patients who are colonized with the bacterium.     

First experience with enteric-coated mycophenolate sodium (Myfortic®) in severe recalcitrant adult atopic dermatitis: an open label study

Background Severe atopic dermatitis (AD) is often treated successfully with oral immunosuppressive drugs such as ciclosporin (CsA) or oral corticosteroids. However, some patients develop adverse effects or are unresponsive to these first‐choice oral immunosuppressive drugs. Objectives To evaluate whether enteric‐coated mycophenolate sodium (EC‐MPS) is an effective treatment in patients with severe, recalcitrant AD. Methods Ten patients with severe, recalcitrant AD were treated with EC‐MPS 720 mg twice daily for 6 months. All patients had to discontinue other oral immunosuppressive drugs due to adverse effects (n = 8) or nonresponsiveness (n = 2). Disease activity was monitored using the Severity Scoring of Atopic Dermatitis (modified SCORAD) index and the Leicester Sign Score (LSS). Additionally, the level of serum thymus and activation‐regulated cytokine (TARC) was measured. During treatment, safety laboratory examination was performed. Total serum immunoglobulin E (IgE) was followed during treatment. Use of topical corticosteroids was recorded before and during treatment. Results Compared with baseline, the mean scores for disease activity significantly decreased during treatment with EC‐MPS [modified SCORAD (P = 0·04), LSS severity (P = 0·01), LSS extent (P = 0·01)]. In addition, serum TARC levels and total serum IgE levels significantly decreased after treatment compared with before (P = 0·03; P = 0·05). Disease activity decreased after approximately 2 months of treatment and stabilized during the 6‐month treatment period. No differences in the amount of topical corticosteroids used in the 6 months prior to treatment compared with the 6‐month treatment period were found (P = 0·4). None of the patients discontinued use of EC‐MPS and only mild adverse effects were seen. Conclusions In this study EC‐MPS at a dose of 720 mg twice daily for 6 months has proven to be an effective and well‐tolerated treatment for patients with severe, recalcitrant AD.     

Efficacy and safety of 'wet-wrap' dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature

BACKGROUND: During the last two decades wet-wrap treatment (WWT) has been advocated as a relatively safe and effective treatment modality in children with severe and/or refractory atopic dermatitis (AD). Unfortunately, there are still many unsolved issues concerning the use of wet-wrap dressings in patients with AD. OBJECTIVES: To make an inventory of the different methodologies and to evaluate the currently available evidence for the use of WWT as an intervention treatment in children with severe and/or refractory AD. METHODS: We performed a search of the literature via the online PubMed database. Reference lists from relevant articles were scanned for additional publications. Publications describing a treatment modality for children with severe and/or refractory AD, which included the application of wet dressings, were collected and evaluated using the guidelines of the NHS Centre for Reviews and Dissemination, University of York. RESULTS: Twenty-four publications were included for evaluation. Eleven of the publications detailed original clinical studies (study design level 2-4), while 13 revealed expert opinions (study design level 5). Evidence levels did not exceed level 4. CONCLUSIONS: Large prospective studies evaluating the efficacy and safety profile of WWT are lacking. We were able to formulate the following conclusions with a grade C of recommendation. (i) WWT using cream or ointment and a double layer of cotton bandages, with a moist first layer and a dry second layer, is an efficacious short-term intervention treatment in children with severe and/or refractory AD. (ii) The use of wet-wrap dressings with diluted topical corticosteroids is a more efficacious short-term intervention treatment in children with severe and/or refractory AD than wet-wrap dressings with emollients only. (iii) The use of wet-wrap dressings with diluted topical corticosteroids for up to 14 days is a safe intervention treatment in children with severe and/or refractory AD, with temporary systemic bioactivity of the corticosteroids as the only reported serious side-effect. (iv) Lowering the absolute amount of applied topical corticosteroid to once daily application and further dilution of the product can reduce the risk of systemic bioactivity.