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Increasing incidence of streptococcal impetigo in atopic dermatitis.

Streptococcal impetigo associated with atopic dermatitis has dramatically increased from 1989 to 1994 in outpatients visiting our hospital, totalling 174 cases. The most frequent causative agents were group A streptococci (Streptococcus pyogenes, 70.7%) followed by group G (19.5%) and group B (9.8%). Streptococcus was isolated singly in 28.2% of cases and in concomitant with Staphylococcus aureus (S. aureus) in 71.8%. Major clinical features of streptococcal impetigo, especially caused by group A streptococci, were non-bullous pustules with thick crusted ceiling. Impetigo caused by group G or B streptococci generally formed smaller sized pustules of fewer numbers. Impetigo was usually present, associated with severe eczematous lesions. Various degrees of fever were noticed in 32.8% (group A, 39.8%; group G, 17.6%; group B, 11.8%) during active stages. The lesions on the face often resembled Kaposi's varicelliform eruption in any group. Systemic antimicrobial agents were administered in 71.3% of cases and the remainder were treated with topical antibiotics (oxytetracycline hydrochloride) or disinfectants (povidone-iodine). Recurrence occurred within a month in 38.0% of cases treated with topical agents only and in 17.7% treated with systemic antimicrobial agents. Antimicrobial susceptibility tests and the results of treatment seem to indicate that cephems, as well as penicillins, are the first choice of treatment for streptococcal impetigo.

Adolescent↗

The epidemiology of atopic dermatitis in Italian schoolchildren.

BACKGROUND: Atopic dermatitis (AD) is common in children in industrialized countries. Only one large population study on its prevalence has been conducted in Italy, based on self-report questionnaire. The present study was designed to estimate the prevalence of AD in schoolchildren in Italy by dermatologists' assessment and by UK Working Party criteria, and to investigate associated symptoms and factors. METHODS: Cross-sectional survey on a random sample of 9-year-old schoolchildren from seven Italian cities. Children were examined by experienced dermatologists. Parents and teachers answered standardized questionnaires. RESULTS: Of the 1369 children examined, 88 had a diagnosis of AD, with an estimated point prevalence of 5.8% (95% CI 4.5-7.1) in the reference population. The reported lifetime prevalence was 15.2 (95% CI 12.2-18.2) for AD, 11.9% (95% CI 9.0-14.8) for asthma, and 17.6% (95% CI 14.6-20.7) for rhino-conjunctivitis. The strongest associated factor was the presence of AD in at least one parent. No association of AD with maternal smoking during pregnancy, birth weight, maternal age at the time of the child birth and breast-feeding was observed. The environmental characteristics of the house and the school did not correlate with the prevalence of AD. Episodes of lower respiratory tract infections were associated with asthma, and to a lower extent also with AD and rhinitis. CONCLUSIONS: The prevalence of doctor-diagnosed AD in Italian schoolchildren is comparable to those reported for other developed countries. Family history of atopy was the single most important associated factor, while the complex interplay of environmental factors remains to be elucidated.

Asthma↗

Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood.

Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLG null variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a chi2 P-value of 1.7 x 10(-53). Our data conclusively demonstrate that identification of FLG null alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.

Adolescent↗

What is the cost of atopic dermatitis in preschool children?

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disorder and an important cause of morbidity in young children in the U.K. Such disability produces significant economic burden reflected in direct medical costs associated with health service utilization, direct family care costs such as transport costs, indirect costs associated with loss of productivity of carers, and intangible costs associated with the psychological effects of the disease. OBJECTIVES: In order to evaluate this economic burden we conducted a cross-sectional survey of children aged 1-5 years in the Nottingham area in 1995-96. METHODS: We sent a postal questionnaire to parents of all children aged 1-5 years with questions to identify those with AD; a second questionnaire was sent to parents of identified children regarding costs and utilization of medical services. Intangible costs were not evaluated. RESULTS: The 12-month period prevalence of AD according to a dermatologist's diagnosis in 1761 children was 16.5% (95% confidence interval 14.7-18.2%). Total mean disease costs were estimated to be pound79.59 per child over the 12-month period of the study. The most significant costs were due to costs to the state for National Health Service (NHS) consultations ( pound28.62 mean annual cost) and prescriptions ( pound22.03). Consultations with general practitioners accounted for the significant bulk of consultation costs, with only 6% of children being seen in secondary care (17 of 290). Most prescribing costs (76%) were due to emollients and bath preparations. Family care costs ( pound28.94 mean annual cost) accounted for 36% of total disease costs and were associated with changes to the home environment, purchase of over-the-counter medicines, transport costs, visits to homoeopaths and salary loss. CONCLUSIONS: The results signify that AD is an important cause of economic burden both to the NHS and to the families of affected children. Using population census data and the results in this study, we estimated that the annual U.K. cost of AD in children aged 1-5 years in 1995-96 was pound47 million.

Age Distribution↗

CD4+ CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease expressed early in life. Disease development is primarily determined by as yet unknown genetic factors, leading to the accumulation of activated T lymphocytes in the skin. OBJECTIVES: To investigate the nature of these T cells. METHODS: T-cell lines could be established from AD skin biopsies, but not from normal skin or AD peripheral blood, when placed in RPMI 1640 medium with 10% human AB serum, antibiotics, and the T-lymphocyte growth factors interleukins 2 and 4. The cell lines were subjected to phenotypic analysis using a fluorescence-activated cell sorter and compared with lymphocytes from AD and normal control peripheral blood. RESULTS: T-cell lines from 22 of 24 consecutive skin biopsies taken from 24 adult patients with AD were established. All cells were T lymphocytes expressing several activation markers. A significant proportion of the lymphocytes had stable expression of a CD4+ CD8+ phenotype (26% +/- 6%; mean +/- SEM). Such double-positive T lymphocytes are normally only seen in the thymus and not in the peripheral immune system. CD4+ CD8+ cells in peripheral blood of the patients (12.5% +/- 3.3%) were also detected. CONCLUSIONS: We suggest that a basic pathophysiological change in AD may be a faulty maturation of the T-lymphocyte system, leading to skin inflammation with CD4+ CD8+ T lymphocytes resembling immature T cells. This is likely to lead to skewing of many immune reactions in the patients.

Adolescent↗

Systemic ketoconazole for yeast allergic patients with atopic dermatitis.

BACKGROUND: Adult patients with atopic dermatitis (AD), especially with the head-neck distribution, are often sensitized to the lipophilic yeast Malassezia furfur/Pityrosporum orbiculare, which is considered to contribute to the pathogenesis of the dermatitis. OBJECTIVE: Evaluation of the efficacy of oral ketoconazole on immunological and clinical parameters in yeast allergic adult patients with AD. STUDY DESIGN: Randomized double-blind placebo-controlled study. SUBJECTS: Twenty-nine patients with specific IgE antibodies to M. furfur/P. orbiculare and with elevated serum IgE participated in the investigation. Fifteen subjects were treated with 200 mg ketoconazole daily and 14 received placebo for 3 months. Betamethasone cream was allowed as supplementary therapy and the consumption was registered. The clinical score (SCORAD), total serum IgE and specific IgE antibodies to M. furfur/P. orbiculare, Candida albicans and Dermatophagoides pteronyssinus were monitored at the starting point and by the end of the first and third month. RESULTS: In the actively treated group the levels of specific IgE to M. furfur/P. orbiculare and C. albicans as well as total serum IgE decreased significantly. Sensitization to D. pteronyssinus was not influenced. The clinical score decreased in both groups, and the improvement was correlated to the consumption of topical steroids in the control group but not in the ketoconazole group.

Adult↗

Association of the IL12RB1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes.

Atopic dermatitis (AD) is frequently associated with eosinophilia, highly elevated immunoglobulin E (IgE) levels and increased levels of T-helper 2-type (Th2) cytokines in skin lesions due to infiltrating T cells. Interleukin-12 (IL-12), in combination with interferon-gamma (IFN-gamma), inhibits IgE synthesis and Th2 cell function. As the IFN-gamma-inducing cytokines IL-12 and IL-23 utilize IL-12Rbeta1 as part of their receptors, it is possible that polymorphic variants of the IL-12Rbeta1 (IL12RB1) gene might determine an individual's susceptibility to AD. Here, we carried out a systemic search for genetic variants of the human IL12RB1 in Japanese subjects and identified 48 genetic variants. In a case-control association study, we found that promoter polymorphisms -111A/T and -2C/T were significantly associated with an increased risk of AD under a recessive model. The -111T-allele frequency in the independent population of child asthmatics was also much higher than that in the control group. In addition, the -111T/T genotype was progressively more common in AD with high total serum IgE levels in an IgE-level-dependent manner. Deletion analysis of the IL12RB1 promoter suggested that the -265 to -104 region that contained the -111A/T polymorphic site harbored an important regulatory element. Furthermore, we showed that the -111A/T substitution appeared to cause decreased gene transcriptional activity such that cells from -111A/A individuals exhibited higher IL12RB1 mRNA levels than those from -111T allele carriers. Our results suggested that in individuals with the -111T/T genotype, reduced IL-12Rbeta1 expression may lead to increased Th2 cytokine production in the skin and contribute to the development of AD and other subsequent allergic diseases.

Adolescent↗

Responsiveness to interleukin 4 and interleukin 2 of peripheral blood mononuclear cells in atopic dermatitis.

Although the pathogenesis of atopic dermatitis (AD) is unknown, many immunologic abnormalities such as high levels of serum IgE and increase of IgE Fc receptor-positive lymphocytes have been demonstrated. Recently, interleukin 4 (IL-4) has been shown to induce enormously the production of IgE and to enhance the expression of IgE Fc receptor by B cells, suggesting the possible involvement of IL-4 in the pathogenesis of AD. We examined IL-4 responsiveness or interleukin 2 (IL-2) responsiveness of peripheral blood mononuclear cells of 31 patients with AD, 19 healthy individuals, and seven patients with other skin diseases. We found that IL-4 responsiveness of AD was higher than that of non-AD control, although IL-2 responsiveness of AD showed no significant change. However, the value of the IL-4 responsiveness did not significantly correlate with the clinical severity, personal history of respiratory allergy, serum IgE level, or clinical course of patients with AD. The hyperresponsiveness to IL-4 detected in AD was not likely to be due to the effects of steroids or anti-mast cell drugs because the value of IL-4 responsiveness was significantly low, compared to AD, in patients with other skin diseases who were treated similarly. Because the T-cell-enriched population, but not the B-cell-enriched population, showed significant proliferation in response to exogenous IL-4 or IL-2, T cells were the main population that reacted in our proliferation assay. These results indicate that IL-4-driven proliferative response may be efficiently operative in T cells in patients with AD.

B-Lymphocytes↗

Clinical effectiveness of a silk fabric in the treatment of atopic dermatitis.

BACKGROUND: In children with atopic dermatitis (AD), eczema is easily aggravated by contact with irritant factors (e.g. aggressive detergents, synthetic and woollen clothes, climatic factors). OBJECTIVES: To evaluate the effectiveness of a special silk fabric (MICROAIR DermaSilk) in the treatment of young children affected by AD with acute lesions at the time of examination. METHODS: Forty-six children (mean age 2 years) affected by AD in an acute phase were recruited: 31 received special silk clothes (group A) which they were instructed to wear for a week; the other 15 served as a control group (group B) and wore cotton clothing. Topical moisturizing creams or emulsions were the only topical treatment prescribed in both groups. The overall severity of the disease was evaluated using the SCORAD index. In addition, the local score of an area covered by the silk clothes was compared with the local score of an uncovered area in the same child. All patients were evaluated at baseline and 7 days after the initial examination. RESULTS: At the end of the study a significant decrease in AD severity was observed in the children of group A (mean SCORAD decrease from 43 to 30; P = 0.003). At the same time, the improvement in the mean local score of the covered area (from 32 to 18.6; P = 0.001) was significantly greater than that of the uncovered area (from 31 to 26; P = 0.112). CONCLUSIONS: The use of special silk clothes may be useful in the management of AD in children.

Acute Disease↗

The effect of dermatology consultations in secondary care on treatment outcome and quality of life in new adult patients with atopic dermatitis.

BACKGROUND: The prevalence of atopic dermatitis (AD) is increasing worldwide, and many patients present to secondary care in adult life. This is a significant contribution to the workload of all dermatology departments. There are no studies investigating the impact of a dermatology consultation within secondary care. OBJECTIVES: To examine the effect of dermatology consultations in secondary care on treatment outcome and quality of life in new adult patients with AD. METHODS: This prospective observational study recruited new adult patients with AD referred from primary care. Eczema severity was assessed using the SCORAD (Severity Scoring of AD) index and subjective good or poor clinical outcome. The Dermatology Life Quality Index (DLQI) was used to quantify the impact of AD on adult patients. Patients were assessed at initial consultation (T1), 6 weeks (T2) and 3 months (T3). Statistical analysis was performed using independent t-tests, repeated-measures analysis of variance, correlation coefficients and Bonferroni post hoc comparisons. RESULTS: Sixty-three patients were recruited (37 women, 26 men) with a mean age of 34 years. Mean SCORAD at T1 was 48.2 and the majority (51%) had severe eczema (objective SCORAD>40). Mean SCORAD reduced by 52% from T1 to T2 (P<0.001) but there was no significant change in SCORAD from T2 to T3. A subjective good clinical outcome was validated by a decrease in SCORAD of >20 (P<0.001). Patients in the good clinical outcome group were significantly older than those in the poor clinical outcome group (38 vs. 27 years, P<0.05). The mean age at presentation of women was significantly younger than men (29 vs. 43 years, P<0.01). Women's mean SCORAD improved over all three visits, while men's mean SCORAD improved from T1 to T2 but worsened from T2 to T3 (P<0.001). The mean DLQI reduced over all three visits, from 9.5 at T1 to 8.8 at T2 and 7.0 at T3, and was significantly correlated with SCORAD at T1 and T2 (P<0.01). Patients accurately self-scored their eczema on a body map as shown by a significant correlation between these scores and SCORAD at T1 and T2 (P<0.001). CONCLUSIONS: We have shown that within the first 3 months of referral to secondary care, new adult patients with AD have the greatest improvement in AD, measured by SCORAD, after their initial appointment. Quality of life, as measured by DLQI, continued to improve over all three visits.

Adolescent↗

A double-blind trial of the H2 receptor antagonist cimetidine, and the H1 receptor antagonist promethazine hydrochloride in the treatment of atopic dermatitis.

Twenty young adults with atopic dermatitis were allocated randomly in a clinical trial to compare the action of the H2 receptor antagonist cimetidine (Tagamet) and the H1 receptor antagonist promethazine hydrochloride (Phenergan), singly and in combination. No significant differences were found, clinically or in the laboratory investigations, between the patients on either drug alone or the combination of the two.

Adolescent↗

Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study.

BACKGROUND: Atopic dermatitis (AD) is a chronic allergic inflammatory disease, which manifests itself with eczematous skin lesions. OBJECTIVE: We compared the clinical efficacy of tacrolimus ointment (0.1%) given twice a day and oral cyclosporine (3 mg/kg) given once daily. Rescue medication for itching included cetirizine 10-20 mg (equal to one or two tables). METHODS: Thirty patients, aged 13-45 years (mean+/-SD 27.1+/-10.9), with a history of moderate-to-severe AD were randomized to treatments, 15 patients for each treatments. Assessment of efficacy was based on SCORAD, on scores of daily itching, erythema, interference with sleep, due to the skin condition and days without use of cetirizine tablets. SCORAD, measured on a scale (0-103), was evaluated before treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment. Similarly, the means of daily symptoms, on a scale (0-3), were evaluated before the treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment; finally, on day without use of cetirizine tablets. The safety of the study treatments was assessed through haematologic, biochemical and urinary testing and on systolic and diastolic blood pressures and heart rate measurements. RESULTS: SCORAD decreased in the two treatment groups 14 days after the beginning of the period study. However, the patients in tacrolimus ointment group reported significantly lower SCORAD than those treated with oral cyclosporine. Overall SCORAD, as assessed by the area under the curve (AUC) day(0-42) (score/day), was significantly lower in the tacrolimus ointment group when compared with oral cyclosporine (P<0.001). Similarly, AUC day(0-42) (score/day) for itching, erythema and number of nights without interference with the sleep due to skin condition were significantly lower in the group of patients treated with tacrolimus compared with those treated with cyclosporine (P=0.003, 0.005 and 0.01, respectively). As regards the use of rescue medication, expressed by median of number of days without use of anti-H(1), it was significantly lower in the group treated with tacrolimus (82.5) than in the cyclosporine group (76.5) (P=0.03). There were no appreciable changes in haematological and biochemical indices, in both treatments groups. CONCLUSION: The results of this comparative study demonstrate that tacrolimus ointment twice daily and cyclosporine administered orally once daily are effective on SCORAD, daily symptoms and anti-H(1) rescue. When we compared tacrolimus and cyclosporine there was a faster onset of action in the group treated with tacrolimus. The two drugs presented the same safety. However, these data support the preferential use of topical tacrolimus 0.1% in AD, because cyclosporine has potential side-effects.

Administration, Oral↗

Correlation of clinical features and skin barrier function in adolescent and adult patients with atopic dermatitis.

BACKGROUND: Xerotic changes in atopic skin are considered to be related to a decrease in the water permeability barrier. Whether abnormal skin barrier function is the main cause of atopic dermatitis (AD) or a secondary change of the disease is still controversial. Noninvasive bioengineering methods, including the measurement of the transepidermal water loss (TEWL) and water capacitance, have been commonly used to evaluate skin barrier function. AIM: To evaluate the correlation between the clinical features of each evaluation site (severity of AD) and skin barrier function. METHODS: TEWL, capacitance, and pH were checked on five evaluation sites: postauricle, forearm, abdomen, thigh, and popliteal fossa. The subjects included 25 patients, both adolescents and adults, with AD and 25 age-matched normal controls. The clinical severity, from 0 (no clinical manifestation) to 3 (severe), was also scored for erythema, induration/papulation, lichenification, and xerosis on each evaluation site of the AD patients. RESULTS: Based on the data, we found that the clinical severity score was correlated with TEWL and capacitance in more than one-half of the evaluation sites. Erythema and induration/papulation showed a statistically significant correlation with TEWL in most cases (P < 0.05, four sites). Lichenification and xerosis showed a significant correlation with capacitance in most cases (P < 0.05, four sites). In most cases, severity scoring of the clinical features did not show a significant correlation with skin pH. The patients showed higher TEWL and lower capacitance than normal controls (P < 0.05, all five sites). CONCLUSIONS: The results of our study suggest that skin barrier function, measured by TEWL and capacitance, and clinical severity show a statistically significant correlation in patients with AD.

Adolescent↗

A study of HLA antigen distribution in families with atopic dermatitis.

Seventeen children presenting with atopic dermatitis were HLA typed together with their parents and siblings. A total of 89 individuals was studied. No close link between HLA antigen distribution and clinical expression of atopy was demonstrated, and 14 HLA identical but disease-free siblings were identified. An increase in the A1 B8 haplotype was observed in the families as a whole by comparison with a large control series.

Adult↗

Interferon-alpha treatment for severe atopic dermatitis.

Patients with both severe atopic dermatitis (AD) and chronic myeloid leukemia, chronic hepatitis B, or chronic hepatitis C were treated with interferon-alpha (IFN-alpha). IFN-alpha treatment improved AD. Moreover, there were also significant decreases in serum IgE and IgG4 levels and in in vitro spontaneous IgE and IgG4 production by patients' mononuclear cells.

Adolescent↗

CD4(+)IL-13(+) cells in peripheral blood well correlates with the severity of atopic dermatitis in children.

BACKGROUND: In atopic dermatitis (AD) a Th1/Th2 imbalance has been reported, and interleukin (IL)-13 seems to play a pivotal role in the inflammatory network. We tried to assess the correlation between the immunological marker CD4(+)IL-13(+) and the clinical phase of extrinsic AD in children. METHODS: Twenty children with AD were studied. Assessed parameters were: clinical severity (SCORAD index), total serum immunoglobulin E (IgE), blood eosinophil count, and percentage of CD4(+)IFNgamma(+), CD4(+)IL-4(+), CD4(+)IL-13(+) T cells. Determinations were carried out in the acute phase and after clinical remission were achieved. Ten nonatopic-matched children served as controls. RESULTS: At baseline, AD was mild in 25%, moderate in 50% and severe in 25% of children. In the acute phase a significant relationship between the eosinophil count and the SCORAD index was found (P = 0.0001). Blood CD4(+)IL-4(+) were significantly higher in the AD group (median 17.0, range: 13.7-21.4) than in controls (12.6, 6.4-17.2, P < 0.0001). CD4(+)IL-13(+) cells in the AD group well correlated (P = 0.0007) with SCORAD index. At remission, a significant correlation between SCORAD index and eosinophil count was found (P < 0.03) and the percentage of CD4(+)IL-13(+) cells globally decreased (P < 0.0001), while no difference was found among SCORAD classes. CONCLUSION: This study confirms the Th2 profile predominance in the peripheral blood of children with AD, and evidences close relationship between the number of CD4(+)IL-13(+) T cells and the disease's severity.

CD4 Lymphocyte Count↗

Low prevalence of the intrinsic form of atopic dermatitis among adult patients.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly associated with respiratory allergies such as rhinitis and asthma, and a high serum level of IgE. In contrast to the 'classic' IgE-mediated allergic (extrinsic) form of AD, approximately 20% of the patients are reported to show normal IgE levels, lack of sensitizations towards environmental allergens, and absence of associated respiratory allergies. Accordingly, these patients are assigned to a nonallergic (intrinsic) form of the disease. OBJECTIVES: In order to define these two forms of AD more closely, 259 adult patients with AD were investigated. RESULTS: After a thorough diagnostic workup there were 18 patients (6.9%), who fulfilled the criteria of intrinsic AD. After follow-up, four additional patients had developed respiratory allergies or IgE-mediated sensitizations resulting in an overall proportion for intrinsic AD of 5.4%. CONCLUSIONS: Based on these figures the nature and relevance of the intrinsic form of AD deserves further evaluation.

Adult↗

Itching from wool fibres in atopic dermatitis.

In 24 girls with atopic dermatitis and a history of irritation to wool, more intense itching was provoked on normal skin on the abdomen by a material with coarse wool fibres (36 microns) than with thinner fibres (20 microns). The probability of the materials causing itching could be predicted by the girls by handling the materials.

Adolescent↗