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PubMed2004

Recent advances in treatment strategies for atopic dermatitis.

A wide range of different therapeutic regimens are used for atopic dermatitis. Although many treatment modalities are well established worldwide among clinicians, only the minority of these therapy recommendations are based on results of randomised controlled trials (RCTs). To close the gap between such 'generally' recommended therapies and therapies that are based on data from controlled trials, this review focuses not only on the pharmacological and clinical aspects of the currently proven agents, but also on the advantages and disadvantages of therapies that have not yet been completely tested.A review of the available literature concerning the pharmacological profile and also the level of evidence of therapeutic efficacy of all currently known topical and systemic agents for the treatment of atopic dermatitis reveals a large gap between the knowledge concerning the pharmacological action in vitro and the evidence of clinical efficacy in many cases. We agree with the conclusion of previous reviews that numerous therapies for atopic dermatitis urgently require more independent RCTs and especially comparative trials (e.g. corticosteroids vs calcineurin inhibitors). These are required in order to facilitate the choice of therapeutic strategy for the individual treatment of atopic dermatitis, with its broad spectrum of clinical manifestations and potential complications in adult patients and, particularly, in children.Finally, we also review preclinical trials with several new drugs. Immunomodulators appear to promise a new dimension for the future of therapy for atopic dermatitis, especially for severe and otherwise refractory forms or as alternatives to corticosteroids, that is, to treat facial atopic eczema without the risk of adverse effects.

Administration, Topical↗
PubMed2005

Changes of epidermal mu-opiate receptor expression and nerve endings in chronic atopic dermatitis.

There is increasing evidence that neuropeptides such as a substance P, neurotrophins or beta-endorphin, an endogenous agonist for mu-opioid receptor, are involved in the pathogenesis of atopic dermatitis in which mental stress and scratching deteriorate the disease. mu-Opioid receptor, a G-protein-coupled receptor, can be downregulated and internalized by agonists and other factors in vitro. In this study, we investigated the regulation of mu-opioid receptor and nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis patients revealed a significant downregulation of mu-opiate receptor expression in epidermis of atopic dermatitis. Permeabilization of the skin showed that the receptor in keratinocytes from atopic dermatitis is internalized. The mRNA expression pattern of the mu-opiate receptor is different in epidermis taken from patients with chronic atopic dermatitis compared to normal skin. In atopic dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis and in normal skin in the suprabasal layers. Staining of the nerve endings using protein gene product 9.5 shows a different pattern of epidermal nerve endings in normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve endings are rather thick. However, in atopic dermatitis, the epidermal nerve endings are thin and run straight through the epidermis. Based on these observations and combining the 'intensity' and 'pattern' hypothesis, we propose a new theory especially for histamine-unrelated, peripheral induction of chronic pruritus. We suggest that 'itch' is elicited in the epidermal unmyelinated nerve C-fibers and 'pain' in the dermal unmyelinated nerve fibers. The downregulation of the opioid receptor in the epidermis contributes to the chronic itching. We call this new hypothesis the 'layer hypothesis'.

Biopsy↗
PubMed2000

Atopic cataracts in a child with atopic dermatitis: a case report and review of the literature.

Cataracts induced by atopic dermatitis rarely occur in adolescent and young adult patients suffering from this problem. Lenticular opacity is an important ocular complication in atopic dermatitis. Although the cause of atopic dermatitis and its ocular complications are unknown, cataracts have been observed to develop and progress during periods of exacerbation of the dermatitis. We report the case of a 16-year-old boy with atopic dermatitis who abruptly developed cataracts in both eyes while suffering from severe skin itching which began 2 months before the initial examination. His peroxidation test result was very high, and we postulate the retinal peroxidation might play a key role in cataractogenesis. Lens aspiration and intraocular artificial lens implantation were performed smoothly with restoration of visual acuity in both eyes.

Adolescent↗
PubMed1999

Validity study for the stigmatization experience in atopic dermatitis and psoriatic patients.

A central experience of patients with atopic dermatitis and psoriasis is the feeling of stigmatization. This can be estimated by the "Questionnaire on Experience with Skin Complaints" (QES), based on the "Feelings of Stigmatization Questionnaire" by Ginsburg & Link. This study was designed to evaluate the psychometric properties of the QES, especially the validity of this questionnaire, and to supply more information about the stigmatization experiences of patients with atopic dermatitis and psoriasis. Three groups of patients were analysed: 76 with atopic dermatitis, 81 and 217 with psoriasis, respectively. The comparison of subgroups with different affected regions revealed that the genital region is especially relevant for the stigmatization experience in these patients. In addition, the feeling of stigmatization (estimated by the QES) is relatively independent of the different dimensions of the "Trier Scales of Coping with Diseases", except for the depressive coping style "Rumination" measuring a high amount of inner concern with the afflicting disease. It can be concluded that the QES is a valid and reliable instrument for examining the stigmatization experience of patients with atopic dermatitis and psoriasis.

Adaptation, Psychological↗
PubMed1983

Decreased release of lysosomal enzymes from peripheral leukocytes of patients with atopic dermatitis.

Peripheral blood leukocytes from fifteen patients with atopic dermatitis and ten normal nonatopic volunteers were incubated with various stimuli in vitro, and the release of the lysosomal beta-glucuronidase into the supernatant was measured. beta-Glucuronidase release was significantly reduced in patients with severe atopic dermatitis after stimulation with aggregated IgG, horse antihuman lymphocyte globulin (ALG), zymosan, and yeast-activated serum. There was an indirect correlation (r = -0.83) between aggregated IgG-induced beta-glucuronidase release and the intensity of clinical symptoms; however, there was no correlation with serum IgE levels. The enzyme release measured was not caused by cellular lysis, except for high concentrations of antilymphocyte globulin, as determined by lactic dehydrogenase (LDH) activity in the supernatant. It is concluded that lysosomal enzyme release defects might be involved in the well-known decreased resistance to infections in patients with atopic dermatitis.

Adolescent↗
PubMed1991

Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.

A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.

Adolescent↗
PubMed1986

Detection of circulating immune complexes in patients with atopic dermatitis and psoriasis.

Sera from 32 patients with atopic dermatitis and 22 patients with psoriasis were examined for the presence of circulating immune complexes (CIC) in comparison to 51 healthy controls using a PEG-precipitation laser nephelometer technique. Different patterns of the precipitated proteins were found in both diseases. In atopic dermatitis C3 and IgG were significantly elevated in CIC. Furthermore, significantly increased amounts of IgE were found in the precipitates. Groups with high and low serum IgE levels showed no significant differences in the quantity of precipitated proteins. Skin involvement did not correlate with CIC. In psoriasis patients, a different pattern with significantly increased IgA, IgG, IgM and C3 was found in the precipitates. IgE was also significantly increased in comparison to the controls. No difference was found between patients with psoriasis vulgaris and psoriasis guttata. CIC in psoriasis and in atopic dermatitis thus showed a characteristic composition. However, a detection of CIC was not directly related to the cutaneous manifestation of the disease.

Antigen-Antibody Complex↗
PubMed1997

Measurement of quality of life in atopic dermatitis: correlation and validation of two different methods.

Atopic dermatitis is a chronic relapsing condition that can have considerable effects on the lives of sufferers. It is apparent that good, valid measures of life quality are necessary for quantifying the patients' perspective of the severity of their disease and the Dermatology Life Quality Index is often employed in clinical research. In a community study of atopic dermatitis we have assessed disability using the Dermatology Life Quality Index and the Patient Generated Index and compared the results from both indices. The results were significantly correlated and reflected the range of disability in patients in the community. Some items of the Dermatology Life Quality Index were not relevant for atopic dermatitis patients in the community and others, including swimming and sleep loss, were often cited in the Patient Generated Index but are not included in the Dermatology Life Quality Index. The Patient Generated Index is a novel, flexible approach to quality of life measurement that may be suitable for reflecting the wide variety of disability that is experienced by dermatological patients.

Activities of Daily Living↗
PubMedDate not supplied

The burden of atopic dermatitis: impact on the patient, family, and society.

Atopic dermatitis is a common disease of increasing prevalence. Affected individuals must cope with a significant psychosocial burden, in addition to dealing with the medical aspects of the disease. Furthermore, because this is primarily a disease of childhood, family members, especially parents, are also affected by the condition. Individuals and family members are burdened with time-consuming treatment regimens for the disease, as well as dietary and household changes. The financial impact of atopic dermatitis on families can also be great. Moreover, the cost to society is significant, with estimates ranging from less than 100 dollars to more than 2000 dollars per patient per year. It is estimated that the direct cost of atopic dermatitis in the United States alone is almost 1 billion dollars per year. Reducing the onus of this disease must take into account the full breadth of its burden. Targeting parents and caregivers with education and psychosocial support can decrease family and personal burden, which in turn may decrease the cost of treating the condition because of better medical, psychosocial, and family outcomes.

Cost of Illness↗
PubMed2001

Differences in efficacy between intention-to-treat and per-protocol analyses for patients with psoriasis vulgaris and atopic dermatitis: clinical and pharmacoeconomic implications.

BACKGROUND: Pharmacoeconomic outcome research is based on three criteria: (i) evaluation of objective therapeutic effects; (ii) quality of life; and (iii) treatment costs. Evaluation of therapeutic effect is mainly based on the results of clinical trials using objective clinical measures, e.g: Psoriasis Area and Severity Index (PASI) (score for psoriasis vulgaris) and the Severity Scoring of Atopic Dermatitis (SCORAD) (score for atopic dermatitis). In most studies, only results for a treatment-optimized subpopulation (patients treated according to the protocol) are presented in publications. The relevance of such data for daily routine therapy is doubtful. OBJECTIVES: Our purpose was to investigate the expected loss of effectiveness of switching from a clinical trial to daily routine therapy for the synchronous application of narrow-band ultraviolet (UV) B phototherapy (311 nm) and bathing in 10% Dead Sea salt solution (synchronous balneophototherapy) for patients with psoriasis vulgaris and atopic dermatitis. METHODS: We conducted a multicentre, uncontrolled observational study of outpatients. To achieve data for 'clinical trial' and 'daily routine' situations, two populations were compared: (i) all patients strictly treated according to the protocol (ATP) with no protocol deviations (data published in clinical trials), and (ii) all patients participating in the study who received active treatment at least once, despite treatment irregularities, non-compliance, early withdrawal or other protocol violations [intention-to-treat-population (ITT), model for 'daily routine']. RESULTS: A total of 2526 patients were included in the ITT analysis for psoriasis vulgaris (n = 487 for atopic dermatitis), of which 818 patients could be analysed according to protocol (n = 104 for atopic dermatitis). Striking differences in the therapeutic effect between both groups (ITT and ATP) were found using relative PASI and SCORAD score improvement: 11% (57% 'daily routine' vs. 68% in 'clinical trial') for psoriasis vulgaris and 16% (39% 'daily routine' vs. 55% 'clinical trial') for atopic dermatitis. The main reasons for excluding patients from the 'clinical trial' group were early study withdrawal in 29% (atopic dermatitis, 47%) of patients and fewer treatments per week than planned in the protocol in 24% (atopic dermatitis, 52%). CONCLUSIONS: Our data clearly indicate that for the prediction of the therapeutic effect for daily routine therapy the ITT data appear to be more relevant than the ATP results (i.e. those presented in clinical trials). Although these data are only a first step for evaluating the 'real' therapeutic effect of a treatment modality in daily routine, they seem to support the requirements for ITT analyses in efficacy studies and demonstrate the necessity of ITT data for pharmacoeconomic evaluation.

Adult↗
PubMed1998

[Atopic dermatitis].

For the past decades, the prevalence of atopic dermatitis is on the rise. Three phases of the disease are recognized according to the age of the patient, either in the newborn age, in infancy or after puberty. A partial enzymatic defect in delta-6 desaturase has been reported. Such metabolic anomaly would be responsible for the alterations in both the skin barrier function and in the Th2 inflammatory reactions in part mediated through IgE. Some microorganisms colonizing the skin play an important causal role in the clinical exacerbations. The influence of food allergy on atopic dermatitis remains obscure and often unconvincing. By contrast, irritant and allergic challenges from the environment exhibit an undisputable worsening effect. The prevention relies on the eviction of predisposing factors and is favourably influenced by emollients specifically designed for atopic dermatitis. A food supplementation in alpha-linoleic acid and some specific chinese herbal remedies might well be useful. The treatment relies primarily on topical applications of corticoids. Puva-therapy, UVB phototherapy and immunomodulation by cyclosporine are indicated for difficult cases.

Administration, Topical↗
PubMed1989

Atopic dermatitis in Nigeria.

The incidence of atopic dermatitis rose from 0.3% in 1962 at the University College Hospital, Ibadan, Nigeria, to 2.6% in 1972. A prospective study was designed to find the incidence nearly three decades after, as well as the presenting clinical features, factors influencing the disease, and the laboratory profile. The analysis of the 64 patients diagnosed during the 1.5-year study period is documented and discussed. The incidence of atopic dermatitis was 6.1%. The increase was attributed partly to increased hospital awareness in this university town and partly to a fall in infective dermatoses. There was paucity of the history of atopic diseases. Sixty-two and one half percent of parents and patients had postprimary education. Two thirds of the people belonged to the middle and high social classes. Self-medication was a frequent finding. No seasonal influence was implicated in 49 cases (76.5%). Heat was the most implicated aggravating factor (21.8%). Postinflammatory dyspigmentation was a common clinical feature. The proportion of patients with significantly high serum IgE stood out clearly.

Adolescent↗
PubMed2005

The occurrence of atopic dermatitis in Greenland.

Until recently there was no information available on the prevalence of atopic dermatitis in Greenland. Our objective was to determine the prevalence of atopic dermatitis in younger schoolchildren in Greenland. In the autumn of 2000 we used our previously elaborated questionnaire in a cross-sectional study of 954 schoolchildren aged 7-8 years, who lived in five Greenlandic towns. The findings were compared to data on atopic dermatitis from Denmark. The response rate was 65% (622). The lifetime prevalence of atopic dermatitis was calculated to be 14.0% (95% confidence interval 11.3-16.7) using our standard score criteria with an absolute lower limit estimate of 4.5%. Taking the response rate of 65% into consideration this study indicates that in 2000 the lifetime prevalence of atopic dermatitis among younger schoolchildren in Greenland was in the range of 10-15%.

Child↗
PubMed2002

In the United States, blacks and Asian/Pacific Islanders are more likely than whites to seek medical care for atopic dermatitis.

BACKGROUND: There have been population-based studies conducted in England and the United States that suggest an increase in prevalence of atopic dermatitis among black and/or Asian children. OBJECTIVE: To assess whether health care utilization for atopic dermatitis differs among different ethnic groups in the United States. DESIGN: Weighted data on representative office visits by whites, blacks, and Asian/Pacific Islanders were analyzed using a cross-sectional study, the National Ambulatory Medical Care Survey (NAMCS), from 1990 through 1998 using statistical software. SETTING: The NAMCS is an ongoing data collection effort by the Division of Health Care Statistics, National Center for Health Statistics, Centers for Disease Control and Prevention. The survey samples representative visits to US office-based physicians during a representative week of practice. PATIENTS: All outpatient visits were analyzed and compared with those for patients diagnosed as having atopic dermatitis (International Classification of Diseases, Ninth Revision, Clinical Modification, code 691.80). MAIN OUTCOME MEASURE: Diagnosis of atopic dermatitis by race. RESULTS: Of 570 million estimated visits for skin conditions, 7.9 million were for atopic dermatitis. The numbers of per capita visits for atopic dermatitis among blacks and Asian/Pacific Islanders were 2-fold and 6-fold higher, respectively, than among whites. The odds ratios (95% confidence intervals) for atopic dermatitis visits by blacks and Asian/Pacific Islanders relative to whites were 3.4 (2.5-4.7) and 6.7 (4.8-9.5), respectively. CONCLUSIONS: Blacks and Asian/Pacific Islanders are much more likely to visit physicians for atopic dermatitis than are whites and may benefit from education and early intervention efforts concerning the disease.

Asian↗