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PubMed1996

Treatment of severe atopic dermatitis in childhood with cyclosporin.

Cyclosporin has been shown to be effective in the treatment of adult atopic dermatitis, but there are no clinical trials evaluating its use in childhood. Atopic dermatitis is more common in children and the severe form can be associated with considerable morbidity. We report on 18 children with severe refractory atopic dermatitis who have been treated with cyclosporin on an open basis. The drug was given at an initial daily dose of 5 or 6 mg/kg and in some patients the dose was reduced according to response. Sixteen patients showed a good or excellent response to treatment, one a moderate response and one patient failed to improve. The treatment was well tolerated and there were no significant changes in serum creatinine or blood pressure. Long remission after withdrawal of treatment was seen in some patients, although most relapsed within a few weeks. We suggest that cyclosporin is an effective and safe short-term treatment for severe atopic dermatitis in childhood.

Adolescent↗
PubMed2003

Long-term remission in patients with dermatitis herpetiformis on a normal diet.

BACKGROUND: A life-long gluten-free diet is the treatment of choice for dermatitis herpetiformis, which is considered to be coeliac disease of the skin. OBJECTIVES: To investigate the effects on long-term remission of dermatitis herpetiformis in patients who underwent a gluten challenge and subsequently reintroduced dietary gluten. PATIENTS AND METHODS: We studied 38 patients (14 male and 24 female) with biopsy-confirmed dermatitis herpetiformis. They had followed a gluten-free diet for a mean of 8 years, achieving clinical remission and intestinal normalization. The patients were asked to reintroduce gluten in their diet and agreed to undergo skin and intestinal biopsies during the follow-up. RESULTS: Of the 38 patients abandoning a gluten-free diet, 31 reported the onset of rash within an average of 2 months. Seven subjects (three males, mean age 15 years at challenge) experienced no clinical or histological relapses (median follow-up 12 years), and lost IgA immunoglobulin from the skin. The two series of patients differed in terms of age at diagnosis (mean age: 26.6 vs. 6 years), the use of dapsone (one of 31 vs. four of seven) and adherence to the gluten-free diet (strict compliance in 26 of 31 vs. none of seven). CONCLUSIONS: Our data suggest that the ingestion of small doses of gluten in childhood and/or the use of an anti-inflammatory drug may modify the immunological response inducing immune tolerance. We report long-term clinical and histological remissions in seven patients with dermatitis herpetiformis after the reintroduction of dietary gluten.

Adolescent↗
PubMed2004

Topical vitamin B12--a new therapeutic approach in atopic dermatitis-evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial.

BACKGROUND: Vitamin B(12) is an effective scavenger of nitric oxide (NO). As the experimental application of a NO synthase inhibitor, N omega-nitro-L-arginine, led to a clear decrease in pruritus and erythema in atopic dermatitis, it would be reasonable to assume a comparable effect of vitamin B(12). OBJECTIVES: The efficacy and tolerability of a new vitamin B(12) cream as a possible alternative to current therapies was examined. METHODS: A prospective, randomized and placebo-controlled phase III multicentre trial, involving 49 patients was conducted. For the treatment duration of 8 weeks, each patient applied twice daily (in the morning and evening) the vitamin B(12)-containing active preparation to the affected skin areas of one side of the body and the placebo preparation to the contralateral side according to the randomization scheme. RESULTS: On the body side treated with the vitamin B(12) cream, the modified Six Area Six Sign Atopic Dermatitis score dropped to a significantly greater extent than on the placebo-treated body side (for the investigational drug 55.34 +/- 5.74 SEM, for placebo 28.87 +/- 4.86 SEM, P < 0.001). At the conclusion of the study, the investigator and patients awarded mostly a 'good' or 'very good' rating to the active drug (58% and 59%, respectively) and a 'moderate' or 'poor' rating to the placebo (89% and 87%, respectively). CONCLUSIONS: Topical vitamin B(12) is a new therapeutic approach in atopic dermatitis. These results document a significant superiority of vitamin B(12) cream in comparison with placebo with regard to the reduction of the extent and severity of atopic dermatitis. Furthermore, the treatment was very well tolerated and involved only very low safety risks for the patients.

Administration, Cutaneous↗
PubMed2005

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

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

Adolescent↗
PubMed1982

Different role of secretory IgA in the pathogenesis of RAST-positive and RAST-negative atopic dermatitis.

Secretory-IgA (SIgA) concentrations were determined in whole saliva, unstimulated or stimulated by lemon juice, of thirty-eight children with atopic dermatitis, which comprised three adolescents, sixteen with IgE detected by RAST to one or more common allergen and twenty-two without specific IgE by RAST. There were thirty healthy controls matched for age and sex. The mean amount of total IgE was significantly greater in the RAST-positive than in the RAST-negative group. The mean SIgA concentration in unstimulated saliva of the RAST-positive atopic dermatitis group was less than that of the RAST-negative atopic dermatitis group and control groups, through the mean concentrations of SIgA of stimulated saliva were not significantly different in the three groups. It is suggested that the pathogenesis of atopic dermatitis may differ in children with or without specific-IgE antibodies; in those who were RAST-positive deficient exclusion of allergen by the intestinal barrier contributed to the pathogenesis, but not in those who were RAST-negative.

Adolescent↗
PubMed1990

Atopic dermatitis: a defect of intracellular secondary messenger systems?

The clinical manifestations of atopic dermatitis comprise a complex mixture of pharmacological, physiological and immunological responses. Circumstantial evidence suggests that atopic disease may arise consequent upon the migration of bone marrow-derived cells into the target tissue of skin or respiratory mucosa. Mediator release from such cells has been shown to be abnormal in atopic dermatitis, and itch, the hallmark of the disease, may be the result of chronic inflammatory mediator release into the skin. Abnormal release of mediators has been shown to correlate with inadequate nucleotide control of cell function. In particular, elevated cyclic AMP-specific PDE activity causing cyclic AMP hyporesponsiveness has been found in peripheral blood mononuclear leucocytes in atopic dermatitis. Investigation of this pathway has led to the discovery of additional abnormalities of other secondary messenger systems, including abnormalities of protein kinase C activity and of inositol activation. The biochemical abnormalities may be a consequence of down-regulation of the second messenger systems because of chronic exposure to low levels of inflammatory mediators, but may themselves subsequently permit further mediator release. They may provide a biochemical mechanism for many of the immunological abnormalities seen in atopic dermatitis. In particular, they offer a biochemical explanation for the paradox of increased type 1-mediated immunity and diminished cell-mediated immunity commonly observed in this complex disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Is the effect of probiotics on atopic dermatitis confined to food sensitized children?

BACKGROUND: Probiotics have previously been shown to reduce the severity of atopic dermatitis (AD) in infants and children. OBJECTIVE: To examine the effect of two probiotics (Lactobacillus rhamnosus and Bifidobacteria lactis) on established AD in children. SUBJECTS AND METHODS: Atopic children with current dermatitis received 2 x 10(10) colony forming units/g of probiotic (n=29) or placebo (n=30). Both were given daily as a powder mixed with food or water. SCORing Atopic Dermatitis (SCORAD; developed by the European Task Force on Atopic Dermatitis) a measure of the extent and severity of AD, was assessed at baseline, 2 and 12 weeks after starting treatment and 4 weeks after treatment was discontinued. RESULTS: SCORAD geometric mean score at baseline was 26.0 (21.9-30.8) in the probiotic group and 35.1 (28.9-42.8) in the placebo group (P=0.02). After adjustment for these between-group baseline differences there was no significant improvement in AD at 12 weeks, SCORAD geometric mean ratio: 0.80 (95% confidence level (CI) 0.62-1.04, P=0.10). Among the food sensitized children, there was an improvement in those treated with probiotics, SCORAD geometric mean ratio: 0.73 (95% CI 0.54-1.00, P=0.047). CONCLUSION: In this study a combination of Lactobacillus rhamnosus and Bifidobacteria lactis improved AD only in food sensitized children.

Bifidobacterium↗
PubMed1990

Blood eosinophilia in atopic dermatitis.

Blood eosinophil levels were examined in 200 (100 mild and 100 severe) patients with atopic dermatitis. Eosinophil levels roughly correlated with disease severity. However, the pattern of eosinophilia was not homogeneous. Very high eosinophil counts were common in severe cases of atopic dermatitis who had a personal or family history of respiratory atopy, while normal or moderately elevated eosinophil values were obtained in severe cases of 'pure' atopic dermatitis who had neither personal nor family history of respiratory atopy. It is suggested that disease severity and personal or family history of respiratory atopy are important factors in determining high blood eosinophil levels in atopic dermatitis.

Adolescent↗
PubMed1994

Production and secretion of interferon-gamma (IFN-gamma) in children with atopic dermatitis.

IFN-gamma is known to be a major inhibitor of IgE synthesis in vitro. Recent studies demonstrating reduced production of IFN-gamma in children and adults with atopic dermatitis and elevated serum IgE suggest a similar role for this cytokine in vivo. The reasons for this reduced IFN-gamma production are not known. One possibility is that atopic individuals have a reduced population of cells producing IFN-gamma in vivo. Using a fluorescence-labelled antibody to detect intracellular IFN-gamma, the percentage of IFN-gamma-producing cells was determined in children with atopic dermatitis and in non-atopic controls. Children with atopic dermatitis had a greater percentage of IFN-gamma-producing cells in unstimulated cultures compared with controls, indicating in vivo activation of lymphocytes in the atopic group. This could reflect the significant degree of inflammation present in these children, or the presence of bacterial infection or colonization. Although secretion of IFN-gamma after stimulation with phorbol myristate acetate (PMA)/Ca was significantly lower in children with atopic dermatitis compared with controls, the percentage of IFN-gamma-producing cells in the stimulated cultures from this group was equivalent to controls. This demonstrates that the reduced ability of atopic children to secrete IFN-gamma in vitro does not relate to a lack of IFN-gamma-producing cells, but to a difference in the regulation of IFN-gamma production beyond the stage of signal transduction.

Adolescent↗
PubMed2004

Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis.

Atopic dermatitis is characterized by Th2-dominant immunity. Recently many intracellular molecules have been reported to regulate cytokine expression and T cell differentiation. GATA-3 and T-box expressed in T cells (T-bet) are transcription factors that play a critical role in the development of Th2 and Th1 immunity, respectively. Suppressor of cytokine signalling (SOCS)-3 and SOCS-5, are negative regulators of the cytokine signalling induced by IL-12 and IL-4, respectively. Txk is a transcription factor that activates IFN-gamma gene directly. The present study was designed to identify intracellular molecules that are responsible for the pathogenesis and the imbalance of cytokines in atopic dermatitis. Semi-quantitative RT-PCR revealed that in peripheral blood mononuclear cells without any stimulation the levels of mRNA for GATA-3 and SOCS-3 were elevated, the levels of mRNA for Txk were depressed and the levels of mRNA for T-bet and SOCS-5 were comparable in patients with atopic dermatitis as compared with healthy controls. In addition, successful therapy normalized levels of mRNA for GATA-3 and Txk, although those for the others including IL-4, IL-5, IL-10, IL-13 and IFN-gamma did not change. Levels of Txk mRNA correlated with those of IFN-gamma, while the mRNA levels of the other regulators did not correlate with those of any of the cytokines. These results suggest GATA-3 and Txk might be involved in skin lesions, while SOCS-3 might be associated with an imbalance of cytokines that is difficult to normalize in atopic dermatitis.

Adolescent↗
PubMed2006

Spontaneous scratching behaviour in DS-Nh mice as a possible model for pruritus in atopic dermatitis.

Itching is one of the major clinical symptoms in atopic dermatitis (AD) and complicates the management of this pathological condition. An animal model of AD-like pruritus would contribute to a better understanding of AD and could lead to the development of safe and effective antipruritic agents. DS non-hair (DS-Nh) mice raised under conventional conditions spontaneously develop pruritus, which is associated with a dermatitis similar to human AD. There is a significant positive correlation between disease severity and the period of scratching behaviour in DS-Nh mice. In the present study, we found that levels of histamine and nerve growth factor (NGF) in serum and/or skin tissue were higher in DS-Nh mice with AD-like dermatitis than in age-matched mice without dermatitis. The histopathological data indicated that nerve fibres extend into and mast cells infiltrate the surrounding area of the skin lesion. NGF production by XB-2 cells, which was derived from mouse keratinocytes, was enhanced by histamine via the H1 receptor. We also found that prolonged treatment with an H1-antagonist was effective against pruritus through depression of the production of NGF, which is thought to be generated by keratinocytes. We conclude that DS-Nh mice can serve as a suitable model for gaining a better understanding of pruritus in AD, and that prolonged treatment with an H1-antagonist may be beneficial in patients with AD-associated pruritus.

Animals↗
PubMed2004

Investigation on the clinical efficacy and safety of 0.1% tacrolimus ointment (Protopic) in canine atopic dermatitis: a randomized, double-blinded, placebo-controlled, cross-over study.

Topical tacrolimus is successfully used in people with atopic dermatitis. Preliminary studies in dogs with atopic dermatitis using tacrolimus in a compounded lotion formulation indicated that tacrolimus significantly decreased erythema and pruritus according to investigator, but no significant improvement was reported by the dog owners. The objectives of this study were to evaluate the clinical efficacy and safety of the commercially available 0.1% tacrolimus ointment (Protopic) in dogs with atopic dermatitis. The study was designed as a double-blinded, placebo-controlled, cross-over study. Selected dogs were allocated to either tacrolimus or placebo for 4 weeks. After 4 weeks there was a wash-out period of 2 weeks and treatments were switched. Twelve dogs completed the study. Clinical signs were scored. Blood samples were collected for complete blood count, chemistry panels and tacrolimus levels at week 0 and 4 of each treatment. Tacrolimus ointment significantly decreased severity of symptoms for both owners and investigators at the end of the trial. When the same dogs received the placebo, there were no differences between week 0 and week 4 scores. Dogs with localized disease responded better than dogs with generalized disease. Tacrolimus was detected in the blood of animals receiving the active ingredient. Levels were below the level of toxicity and no adverse effects were reported in any of the dogs. No changes in complete blood count and chemistry parameters were detected between groups or within groups. In conclusion, tacrolimus appears to be a safe alternative treatment in dogs with atopic dermatitis, especially in those with localized disease.

Administration, Cutaneous↗
PubMed2005

Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis - a pilot study.

This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA complexes combined with specific allergens for immunotherapy of refractory canine atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. Further investigations in larger numbers of dogs with earlier stages of disease are warranted.

Adjuvants, Immunologic↗
PubMed2006

Comparison of clinical history and dermatologic findings in 29 dogs with severe eosinophilic dermatitis: a retrospective analysis.

The medical records and histopathological sections of 29 dogs diagnosed with a unique eosinophilic dermatitis resembling Wells' syndrome were reviewed in an attempt to elucidate the pathogenesis of this syndrome. The medical records were reviewed for information on dermatological lesion appearance, systemic signs in other organ systems, clinical analyte abnormalities, and drug therapy. Histological sections of dogs with moderate to severe eosinophilic dermatitis without folliculitis and furunculosis were reviewed and evaluated for the presence of collagen flame figures. Three categories of patients were found. Category 1 consisted of 17 dogs treated for vomiting and/or diarrhoea (often haematochezia or haematemesis) prior (mean: 4.6 days) to the onset of skin lesions. Fourteen category 1 dogs had erythematous lesions (macules, papules or plaques) that were most pronounced on the abdomen. Sixteen of the 17 dogs received multiple classes of drugs, and 59% were hypoalbuminemic. Category 2 consisted of five dogs that had skin lesions and gastrointestinal signs at presentation and four of these dogs were hypoalbuminemic. Category 3 included seven dogs without enteric illness. A positive drug score was found in six category 1 dogs and one each from categories 2 and 3. Eighteen cases had eosinophilic dermatitis without flame figures, seven cases had early flame figures and four had well-developed flame figures. These changes did not correlate with the categories of clinical presentation. More than 50% of the dogs developed eosinophilic dermatitis following treatment for severe gastrointestinal disease. The authors propose that this represents a unique syndrome that may have causal drug association.

Animals↗
PubMed1975

Recurrent contact dermatitis caused by mercury in amalgam dental fillings.

A metal worker had repeated episodes of contact dermatitis over a period of years. Patch tests with 5% ammoniated mercury were strongly positive but occupational contact could not be proved. Recurrence of the dermatitis one day after amalgam dental fillings had been made and again one year later, this time without new fillings, raised the possibility that it was due to the old amalgam fillings. Removal of all the amalgam fillings resulted in a new outbreak of severe dermatitis; during the 5 years ensuing there has been no recurrence. This case history suggests that contact dermatitis may be caused by not only the mercury in new fillings but also by that in old fillings.

Adult↗
PubMed1993

Role of emotional factors in adults with atopic dermatitis.

BACKGROUND: The role of anger in the onset or perpetuation of episodes of atopic dermatitis in adults has long been considered an important factor. The objective was to investigate whether atopic patients feel ineffective in dealing with anger and assertiveness when compared with psoriasis patients and control patients. METHODS: Thirty-four adult patients with atopic dermatitis were compared to 28 patients with psoriasis and 32 controls, dental patients without major skin disease. Standard measures of anxiety, anger, assertion, depression, and locus of control as well as a measure of anger effectiveness, designed for this study, were used. RESULTS: There were significant differences between atopic dermatitis patients and controls in that atopics felt angry more readily but were less likely to express it, were more anxious and less assertive, and felt less effective in expressing anger. The only difference between psoriasis patients and controls was less ability to express anger. Atopic patients were more chronically anxious than those with psoriasis. CONCLUSIONS: Adult atopic dermatitis patients are often chronically anxious and feel ineffective in handling anger which suggests that psychological interventions may prove helpful.

Adolescent↗
PubMed2006

Ciclopirox 1% shampoo for the treatment of seborrheic dermatitis.

Seborrheic dermatitis is a chronic superficial fungal infection of the skin, particularly affecting sites rich in sebaceous glands. Although the precise etiology of seborrheic dermatitis is uncertain, yeasts of the genus Malassezia are known to play a causative role. Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent, which also has anti-inflammatory properties. Ciclopirox is effective both in vitro and in vivo against Malassezia yeasts, making it a valuable option for the treatment of seborrheic dermatitis. Varying frequencies and concentrations of ciclopirox shampoo have been shown to be effective and safe in the treatment of seborrheic dermatitis of the scalp.

Administration, Topical↗
PubMed2006

Human arylamine N-acetyltransferase 2 polymorphism and susceptibility to allergic contact dermatitis.

BACKGROUND: N-acetyltransferase 2 (NAT2) polymorphism may be involved in the pathogenesis of allergic contact dermatitis. OBJECTIVE: The present study was designed to evaluate whether acetylation polymorphism plays a role in the susceptibility to p-Phenylenediamine (PPD) sensitization. METHODS: The frequencies of seven NAT2 point mutations, namely G191A, C282T, T341C, C481T, G590A, A803G, and G857A, and genotypes were determined by PCR/RFLP in a total of 70 patients with allergic contact dermatitis to PPD and 100 control subjects with no history of allergy, atopy, lung disease, diabetes mellitus and cancer. RESULTS: Genotypes coding rapid acetylation were detected in 52.9% and 37.0% of patients with contact dermatitis and control subjects, respectively (P = 0.04). The frequency of the NAT2*4 allele and NAT2*4/*4 genotype, coding for rapid acetylation, were also significantly higher in the contact dermatitis patients than in the control subjects (P = 0.003). CONCLUSION: Our results suggest an association between rapid acetylation polymorphism and susceptibility to PPD sensitization.

Acetylation↗