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PubMed1993

Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample.

BACKGROUND: Atopic dermatitis is a common multifactorial disease that seems to be increasing in frequency. OBJECTIVE: Our purpose was to evaluate and expand previous findings on the incidence of atopic dermatitis and its concordance rates in twins. METHODS: A mailed questionnaire study was conducted. It involved 812 twin pairs living in Fyn County, Denmark, as of Jan. 1, 1987 and born between 1965 and 1979. Zygosity was determined by the similarity method. RESULTS: The response rate was 92%. The cumulative incidence rate (up to 7 years) of atopic dermatitis increased significantly from 0.06 for the birth cohort 1965-1969 to 0.12 for the birth cohort 1975-1979. The pairwise concordance rate was 0.72 in monozygotic and 0.23 in dizygotic twin pairs. CONCLUSION: The frequency of atopic dermatitis is still increasing but not as rapidly as in the 1960s. The magnitude of the concordance rates indicates that genetic factors are decisive in the development of atopic dermatitis. It is suggested that widespread environmental factors are operating in genetically susceptible persons.

Adolescent↗

PubMed1981

Enumeration of T cell subsets in atopic dermatitis using monoclonal antibodies.

Peripheral blood lymphocytes from 22 patients with atopic dermatitis, 17 age-matched healthy controls, 10 patients with other skin diseases, and 14 patients with either asthma or allergic rhinitis were characterized by reactivity with monoclonal antibodies to the surface antigens of helper-inducer (T4) and suppressor-cytotoxic (T8) T cell subsets and to a common T cell antigen (T3). In contrast to healthy controls and controls with other skin diseases or respiratory allergic disease, patients with atopic dermatitis had a reduced percentage of T3-positive (T3+)cells (p less than 0.01) and T8-positive (T8+) cells (p less than 0.001) but not of T4-positive cells (T4+)op less than 0.05). A selective increase in the ratio of T4+ cells over T8+ cells was observed in 17 of 22 patients with atopic dermatitis but not in any of the controls. Thus there is a loss of circulating suppressor-cytoxic T cells in the majority of patients with active atopic dermatitis.

Adolescent↗

PubMed1994

Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. The Doxepin Study Group.

BACKGROUND: Atopic dermatitis is associated with severe pruritus for which effective topical treatment is lacking. As a potent H1 and H2 antagonist, the antipruritic effect of topical doxepin was first demonstrated in histamine-induced itch in nonatopic volunteers. OBJECTIVE: The current study was undertaken to compare the efficacy and safety of topical 5% doxepin cream in relieving pruritus associated with atopic dermatitis. METHODS: A total of 270 patients with atopic dermatitis who had daily moderate to severe pruritus for at least 1 week were enrolled in the double-blind, vehicle-controlled, multicenter study. Treatment was randomly assigned: 5% doxepin cream or vehicle cream was applied twice on the day of the baseline visit and four times daily for the remainder of the 7-day trial. RESULTS: Relief of pruritus was achieved in 85% of doxepin-treated patients and 57% of vehicle-treated patients by day 7; a majority of these positive responses occurred during the first 24 hours. Pruritus severity scores demonstrated significantly greater improvement with topical doxepin at each study visit (p < 0.01). Visual analogue scales for pruritus severity and pruritus relief showed similar improvement in the doxepin-treated group. At each of three visits, the physician's global evaluation for relief of pruritus also showed significant improvement in the doxepin treatment group (p < 0.01). The physician's global evaluations of eczema significantly favored topical doxepin on day 7 (p < 0.01). Nineteen patients withdrew from the study because of adverse effects (doxepin, n = 16; vehicle, n = 3). The most commonly reported were localized stinging or burning (doxepin group, n = 39; vehicle group, n = 34) and drowsiness (doxepin group, n = 37; vehicle group, n = 3), all of which decreased in frequency and severity over time. CONCLUSION: Topical doxepin is effective in reducing pruritus in patients with atopic dermatitis. It has an apparent short-term low risk of major side effects or sensitization.

Administration, Cutaneous↗

PubMed2001

Double-blinded, placebo-controlled, cross-over pilot study on the efficacy of zileuton for canine atopic dermatitis.

Nine dogs meeting the diagnostic criteria for canine atopic dermatitis were enrolled in a double-blind, placebo-controlled, cross-over clinical trial. In this pilot study, zileuton (a 5-lipoxygenase inhibitor) given orally at 2 mg kg(-1) three times daily for 4 weeks significantly decreased erythema in dogs with atopic dermatitis but had no effect on pruritus. Zileuton was well tolerated and no adverse clinical signs were noted. However, one dog developed mild alanine aminotransaminase elevation, which resolved within 1 week of discontinuation of therapy. Monitoring of alanine aminotransaminase may be necessary in dogs receiving zileuton. Further studies with larger number of dogs are needed to evaluate the efficacy of zileuton as treatment for canine atopic dermatitis.

Administration, Oral↗

PubMed1997

Efficacy trial of bioresonance in children with atopic dermatitis.

Single case reports and uncontrolled studies claim significant improvements in patients with atopic diseases treated with bioresonance therapy, also called biophysical information therapy (BIT). To assess the efficacy of this alternative method of treatment, we performed a conventional double-blind parallel group study in children hospitalized for long-lasting atopic dermatitis. Over a period of 1.5 year, 32 children with atopic dermatitis, age range 1.5-16.8 years and hospitalized for 4-6 weeks at the Alpine Children's Hospital Davos, Switzerland, were randomized according to sex, age and severity of the skin disease to receive conventional inpatient therapy and either a putatively active or a sham (placebo) BIT treatment. Short- and long-term outcome within 1 year were assessed by skin symptom scores, sleep and itch scores, blood cell activation markers of allergy, and a questionnaire. Hospitalization and conventional therapy in a high altitude climate resulted in immediate and sustained amelioration of the disease state in both the BIT-treated and sham-treated groups. BIT had no significant additive measurable effect on the outcome variables determined in this study. The statement by protagonists of this alternative form of therapy that BIT can considerably influence or even cure atopic dermatitis was not confirmed using for the first time a conventional double-blind study design. Considering the high costs and false promises caused by the promotors of this kind of therapy, it is concluded that BIT has no place in the treatment of children with atopic dermatitis.

Adolescent↗

PubMed1985

[The concept of disease in patients with atopic dermatitis].

34 former patients of a dermatological department with atopic dermatitis were compared with 29 patients of an Ear-Nose-Throat-department having similar age, sex and occupation and showing hardly any psychosomatic disturbances. Contrary to our expectations, the empiric-psychological examination did not reveal any impairment of the social behavior or the emotional competence of patients suffering from atopic dermatitis. In comparison to the control group, the patients of the dermatological department attached significantly greater importance to psychological influences on development as well as treatment of the disease. There was a correlation between symptoms "coming from outside" and the social competence; however, this correlation was not significantly greater than the control group. Our investigations suggest that atopic dermatitis may be differentiated into somatical-organizing types and rather psychological-organizing types. The second group shows uncertainties with regard to the social competence.

Age Factors↗

PubMed2001

Anti-mycotics suppress interleukin-4 and interleukin-5 production in anti-CD3 plus anti-CD28-stimulated T cells from patients with atopic dermatitis.

It is reported that anti-mycotic agents are effective for the treatment of patients with atopic dermatitis. We studied the in vitro effects of anti-mycotics on T helper-1 and T helper-2 cytokine production in anti-CD3 plus anti-CD28-stimulated T cells from atopic dermatitis patients and normal donors. The amounts of interleukin-4 and interleukin-5 secreted by anti-CD3/CD28-stimulated T cells were higher in atopic dermatitis patients than in normal donors. Azole derivatives, ketoconazole, itraconazole, miconazole, and nonazole terbinafine hydrochloride, and tolnaftate reduced interleukin-4 and interleukin-5 secretion without altering that of interferon-gamma and interleukin-2 in anti-CD3/CD28-stimulated T cells from both atopic dermatitis patients and normal donors. The azole derivatives were more inhibitory than nonazole anti-mycotics. These anti-mycotics reduced the anti-CD3/CD28-induced mRNA expression and promoter activities for interleukin-4 and interleukin-5. The 3',5'-cyclic adenosine monophosphate analog dibutyryl 3',5'-cyclic adenosine monophosphate reversed the inhibitory effects of the anti-mycotics on interleukin-4 and interleukin-5 secretion, mRNA expression, and promoter activities. Anti-CD3/CD28 transiently (< or = 5 min) increased intracellular 3',5'-cyclic adenosine monophosphate in T cells, and the increase was greater in atopic dermatitis patients than in normal donors. The increase of 3',5'-cyclic adenosine monophosphate by anti-CD3/CD28 correlated with interleukin-4 and interleukin-5 secretion by anti-CD3/CD28. The transient 3',5'-cyclic adenosine monophosphate increase was suppressed by anti-mycotics, and azole derivatives were more suppressive than nonazoles. Azole derivatives inhibited the activity of cyclic adenosine monophosphate-synthesizing adenylate cyclase whereas terbinafine hydrochloride and tolnaftate enhanced the activity of 3',5'-cyclic adenosine monophosphate-hydrolyzing cyclic nucleotide phosphodiesterase in atopic dermatitis and normal T cells. These results suggest that the anti-mycotics may suppress interleukin-4 and interleukin-5 production by reducing 3',5'-cyclic adenosine monophosphate signal, and stress their potential use for the suppression of T helper-2-mediated allergic reactions.

Adenylyl Cyclases↗

PubMed1979

An in vitro study of IgE production in severe atopic dermatitis.

Peripheral blood lymphocytes from 4 patients with severe atopic dermatitis and with high serum IgE levels produced measurable amounts of IgE in vitro in repeated tests. These patients had increased numbers of IgE-bearing peripheral blood lymphocytes on at least one test occasion. No measurable IgE production in vitro was found in 6 other patients with atopic dermatitis and in 3 healthy controls. Inhibition of the IgE production was observed following treatment with PHA, Con A, PWM, mixed lymphocyte culture and radiation. LPS and histamine induced neither definite stimulation nor inhibition of IgE production. Supernatants from Con A stimulated cells were used in tests for suppressor factors. The hypothesis that depressed suppressor function of the T cells might be responsible for the tendency to increased IgE production in atopic dermatitis is discussed.

Adult↗

PubMedDate not supplied

Heterogeneity of dermal deposition of eosinophil granule major basic protein in acute lesions of atopic dermatitis.

Deposition of eosinophil granule major basic protein (MBP) often occurs in acute and chronic lesions of atopic dermatitis, but it is not clear what the factors may be that are related to the MBP deposition in some skin lesions of the disease. The purpose of this study was to determine whether a personal or family history of respiratory atopy is related to the intensity of MBP deposition in acute lesions. We immunohistochemically stained biopsy specimens from acute, non-oozing indurated erythematous lesions of atopic dermatitis with BMK-13, a monoclonal antibody which recognizes MBP. The subjects were 40 adult patients with atopic dermatitis. Of the 40 patients, 22 had a personal history of respiratory atopy, 8 had a family history of respiratory atopy, and 10 had neither a personal nor a family history of respiratory atopy. Deposition of MBP was observed in the specimens from 24 (60%) of the 40 patients examined. Furthermore, there were great individual differences in the intensity of MBP deposition. A strong MBP deposition was often seen in specimens from patients with atopic dermatitis who had a personal or family history of respiratory atopy, but was absent in specimens from those patients with atopic dermatitis who had neither a personal nor a family history of respiratory atopy. We conclude that a strong MBP deposition seems to occur in acute lesions of those patients with atopic dermatitis who have a predisposition to respiratory atopy.

Acute Disease↗

PubMed1994

Circulating ICAM-1 levels in children with atopic dermatitis.

Circulating intercellular adhesion molecule-1 (ICAM-1) levels were measured in 48 patients with atopic dermatitis (mild in 29, moderate in 13, and severe in 6) and in 32 controls. Circulating ICAM-1 levels gradually increased with the severity of atopic dermatitis (216 +/- 68 in control, 323 +/- 66 in mild, 376 +/- 92 in moderate, and 555 +/- 93 ng/mL in severe atopic dermatitis, respectively). A significant correlation was observed between serum ICAM-1 and eosinophilic cationic protein levels in patients with atopic dermatitis (r = .71, P < .01). Although a significant positive correlation was observed between serum eosinophilic cationic protein levels and peripheral eosinophil counts (r = .63, P < .01), only a weak correlation was observed between serum ICAM-1 levels and peripheral eosinophil counts (r = .35, P < .05). Changes in serum ICAM-1 levels in ten patients treated with ketotifen for 3 months were also demonstrated. A close correlation was observed between serum ICAM-1 levels and the disease severity (r = .76, P < .01). From these results, we speculate that serum ICAM-1 level may reflect the extent of inflamed tissue in atopic dermatitis.

Blood Proteins↗

PubMedDate not supplied

Can atopy patch tests with aeroallergens be an additional diagnostic criterion for atopic dermatitis?

UNLABELLED: The complex pathomechanisms underlying skin lesions in atopic dermatitis (AD) result in variations of the clinical picture and frequent diagnostic difficulties. The purpose of this study was to evaluate the usefulness of atopy patch tests (APT) for aeroallergens in the diagnosis of AD. The study involved 115 adult patients with AD and 98 healthy volunteers (the control group). APTs for cat dander allergens, birch pollen, a mixture of house dust mite species and a mixture of 5 grass pollen allergens were applied for both groups. Positive reaction to at least one test allergen was found in 53.9% patients compared to 6.2% in the control group (p<0.001). The most frequent hypersensitivity (45.2%) observed was to house dust mite allergens. Polyvalent allergy to 2-4 allergens was found in 56.5% patients. The specificity of tests exceeded 75%, whereas the sensitivity varied from 18 to 66%. CONCLUSIONS: 1. Atopy patch tests, which are characterised by considerable specificity, confirm the role of polyvalent contact hypersensitivity to aeroallergens in the development of atopic dermatitis. 2. Positive aeroallergen ATP results are observed in the majority of patients and can thus be regarded as an additional diagnostic criterion in atopic dermatitis.

Adolescent↗

PubMed1992

Genetic risk for asthma, allergic rhinitis, and atopic dermatitis.

In order to explore the genetic risk of a child with a family history of allergies developing asthma, allergic rhinitis, or atopic dermatitis, questionnaires filled in by 6665 families were analysed. The data were collected in a population based cross sectional survey of 9-11 year old schoolchildren living in Munich and southern Bavaria. The relation between asthma, allergic rhinitis, and atopic dermatitis and the number of allergic first degree relatives, and the type of allergic disease was examined. Analyses were done separately for families with single or multiple allergic diseases. In families with one allergic parent the risk of the child developing asthma was increased by asthma in a parent, with an odds ratio (OR) of 2.6 (95% confidence interval 1.7 to 4.0) but not by parental allergic rhinitis with OR 1.0 (0.7 to 1.5) or atopic dermatitis, OR 1.0 (0.6 to 1.6). For allergic rhinitis the highest risk with OR 3.6 (2.9 to 4.6) was observed with allergic rhinitis of one parent, apparently lower for asthma of one parent, OR 2.5 (1.6 to 4.0) or atopic dermatitis, OR 1.7 (1.1 to 2.5). Children with parental atopic dermatitis had a high risk for atopic dermatitis, OR 3.4 (2.6 to 4.4), compared with children with parental asthma, OR 1.5 (1.0 to 2.2), or parental allergic rhinitis, OR 1.4 (1.1 to 1.8). Risk factors in families with combined allergies of two relatives (parents and siblings) were analysed separately for the different combinations. These results support the hypothesis that asthma, allergic rhinitis, and atopic dermatitis are multifactorial diseases brought about by various familial and environmental influences.

Asthma↗

PubMedDate not supplied

[Clinical trials in dermatology. Evaluation of the tolerability and efficacy of a topical anti-inflammatory treatment in atopic dermatitis].

Study designs for assessment of topical anti-inflammatory drugs in atopic dermatitis are discussed. Atopic dermatitis is a chronic disease with symmetrically distributed lesions. In order to avoid individual and spontaneous variation and to obtain an early impression of the efficacy of a new topical drug, bilaterally paired lesions can be used. Further drug development requires controlled double-blind parallel group design. General recommendations regarding inclusion criteria, and the measurement of efficacy and safety parameters are presented. Methods available for data evaluation and the particularities of different clinical designs are discussed.

Administration, Topical↗

PubMed1987

Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis.

Cloth diapers, cellulose core diapers (conventional disposable diapers), and cellulose core diapers containing absorbent gelling material were examined for their effects on diaper rash and skin microbiology of normal infants and infants with atopic dermatitis in a 26-week double-blind clinical trial. Infants with atopic dermatitis wearing the diapers containing absorbent gelling material had significantly lower diaper rash grades than infants with atopic dermatitis wearing cloth diapers at five of eight grading visits. Infants with atopic dermatitis wearing conventional cellulose core diapers had statistically less rash at one of eight visits. There was no statistically significant difference between diaper types at three of the eight visits. At no time did the cloth group have less diaper rash than the conventional cellulose or absorbent gelling material disposable diaper group. A statistical correlation between the severity of general atopic dermatitis outside the diaper area and the diaper rash condition under the diaper occurred only in the atopic dermatitis group wearing cloth diapers. Isolation of microorganisms from the intact, uninvolved skin surface both inside and outside the diaper showed no biologically significant changes in the presence or numbers of selected skin organisms. Repeated isolation, at multiple grading visits of Staphylococcus aureus from uncompromised skin inside the diaper area was infrequent but correlated with the diagnosis of atopic dermatitis when observed.

Acrylic Resins↗

PubMed2004

Allergen-specific immunotherapy induces Th1 shift in dogs with atopic dermatitis.

Allergen-specific immunotherapy has been applied to canine atopic dermatitis. Despite the accumulated clinical evidence of its effect for atopic dogs, the basic immunologic mechanisms were not fully understood. In this study, the cytokine profile ex vivo in canine atopic dermatitis before and after allergen-specific immunotherapy was characterized using competitive reverse transcription-polymerase chain reaction (RT-PCR). Blood samples were collected from 10 dogs with atopic dermatitis and peripheral blood mononuclear cells were stimulated with house dust mite antigen. The levels of IFN-gamma and IL-4 mRNA were lower in atopic dogs compared with non-atopic controls. The ratio of IFN-gamma/IL-4 was low in atopic dogs indicating a cytokine profile polarized to Th2. The level of IFN-gamma after immunotherapy was significantly higher than that before (P < 0.05) whereas that of IL-4 mRNA was not changed. Consequently, the ratio of IFN-gamma/IL-4 after immunotherapy was significantly higher than that before immunotherapy (P < 0.05). These results indicate a Th2 cytokine bias is the dominant state in atopic dogs and allergen-specific immunotherapy causes a shift to wards a Th1 bias by enhancing IFN-gamma expression.

Animals↗

PubMed1995

Antigen presenting cell-independent cytokine and spontaneous in vitro IgE production in patients with atopic dermatitis: increased interferon-gamma production and lack of effects of in vivo low-dose interferon-gamma treatment.

Atopic dermatitis is characterized by elevated serum IgE concentrations and dysregulation of T-lymphocyte function. To examine the pattern of cytokine production associated with elevated IgE levels, phorbol ester plus ionomycin-stimulated production of interleukin (IL)-4, IL-5, and interferon-gamma (IFN-gamma) by blood mononuclear cells from 16 patients with atopic dermatitis was compared with that of 18 healthy subjects. Spontaneous in vitro IgE production was also studied longitudinally in patients receiving placebo or daily treatment with 0.05 mg/m2 IFN-gamma. Spontaneous in vitro IgE production and mitogen-driven IL-4 and IFN-gamma synthesis did not differ when patients were receiving interferon treatment compared with no treatment. Furthermore, ionomycin plus phorbol ester-stimulated mononuclear cells from patients with atopic dermatitis produced less IL-4 and more IFN-gamma than did cells from healthy subjects. IL-5 production by cells from patients with atopic dermatitis did not differ from that of cells from healthy subjects. The ratio of IL-4 to IFN-gamma produced in vitro was significantly lower (p = 0.04) in the cells of patients with atopic dermatitis (0.9) as compared with those of healthy subjects (2.7). The findings suggest that when circulating T cells are stimulated under antigen presenting cell-independent conditions, atopic dermatitis is not characterized by the shift in the reciprocal relationship between IL-4 and IFN-gamma production, which has been postulated to explain the pathogenesis of IgE elevation and the therapeutic action of IFN-gamma in patients with atopic dermatitis.

Adult↗

PubMed1991

Nocturnal growth hormone release in children with short stature and atopic dermatitis.

This study was designed to test the hypothesis that children with atopic dermatitis and short stature fail to release growth hormone after falling asleep. Peak serum growth hormone response to arginine was compared with peak growth hormone concentration during sleep in 6 children with atopic dermatitis and short stature (greater than 3 SD below the mean) aged 7 to 12 years, and 5 control children aged 9 to 12 years without atopic dermatitis or asthma but with unexplained short stature (greater than 3 SD below the mean). All 5 control children achieved normal levels of growth hormone after falling asleep, whereas 3 of the 6 children with dermatitis did not. All patients with dermatitis were capable of releasing growth hormone after arginine stimulation. The results suggest that in some prepubertal children with atopic dermatitis and short stature there may be an impairment of growth hormone release during stage 4 sleep.

Arginine↗

PubMedDate not supplied

A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid-based lipid infusion in atopic dermatitis.

BACKGROUND: In the involved epidermis of patients with atopic dermatitis, changes in the metabolism of eicosanoids with increased quantities of the arachidonic acid (AA)-derived lipoxygenase products have been observed. Free eicosapentaenoic acid (EPA), a fish oil-derived alternative (n-3) fatty acid, may compete with AA, resulting in an anti-inflammatory effect. METHODS: In a 10-day double-blind, randomized, placebo-controlled trial, 22 patients hospitalized for moderate-to-severe atopic dermatitis were randomly assigned to receive daily infusions of either a n-3 fatty acid-based lipid emulsion (fish oil, 10%; 200 mL/d) or a conventional n-6-lipid emulsion (soybean oil, 10%; 200 mL/d). Topical treatment was restricted to emollients. The severity of disease was evaluated daily with scoring of erythema, infiltration, and desquamation and by subjective patient scoring of clinical manifestations. In addition, plasma-free and total-bound fatty acids and the composition of membrane fatty acids in blood cells (thrombocytes, granulocytes, and erythrocytes), lipid mediators from isolated neutrophils and platelets, and lymphocyte-activation parameters were determined. RESULTS: Twenty patients completed the trial. Marked improvement from baseline was seen in both groups. On days 6, 7, 8, and 10, disease severity score-defined as the sum of all scores-was more pronounced (p < .05) in the n-3 group compared with the n-6 group. Free arachidonic acid in plasma did not change substantially in both groups, whereas plasma-free EPA, total-bound EPA, and the membrane EPA/AA ratio markedly increased in response to n-3-lipid infusion. In parallel, EPA-derived lipid mediators appeared, whereas lymphocyte functions were unaffected. In the post-treatment period (2/4 weeks), relapse was observed in some patients after n-3 psoralene-ultraviolet A (PUVA) infusion, whereas there was a marked long-term improvement in the n-6 group. CONCLUSIONS: IV n-3-fatty acid administration is effective in acutely improving the severity of atopic dermatitis, paralleled by changes in plasma and membrane fatty acid composition and lipid mediator synthesis. The long-term beneficial effects of IV n-6 fatty acids should be evaluated further.

Adolescent↗