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Randomized comparison of the type 4 phosphodiesterase inhibitor cipamfylline cream, cream vehicle and hydrocortisone 17-butyrate cream for the treatment of atopic dermatitis.

BACKGROUND: Therapeutic options to treat atopic dermatitis are limited. Leukocytes from atopic patients have an abnormally high activity of cyclic adenosine monophosphate (AMP)-phosphodiesterase (PDE), which can be normalized in vitro by PDE inhibitors. Cipamfylline is a new potent and selective inhibitor of PDE-4. OBJECTIVES: To compare the efficacy and safety of up to 14 days' topical treatment with cipamfylline (0.15%) cream with vehicle and with hydrocortisone 17-butyrate (0.1%) cream. PATIENTS AND METHODS: International, multicentre, prospective, randomized double-blind, left-right studies of cipamfylline vs. vehicle and cipamfylline vs. hydrocortisone 17-butyrate in adult patients with stable symmetrical atopic dermatitis on the arms. RESULTS: Both cipamfylline and hydrocortisone 17-butyrate reduced the Total Severity Score significantly (P < 0.001). The reduction with cipamfylline was significantly greater than that with vehicle (difference vehicle-cipamfylline 1.67 95% confidence interval (CI) 1.06, 2.28; P < 0.001) and was significantly less than with hydrocortisone 17-butyrate (difference hydrocortisone-cipamfylline -2.10 95% CI -2.93, -1.27; P < 0.001). Investigator and patient assessments of the overall treatment response showed a similar picture. CONCLUSIONS: Cipamfylline cream is significantly more effective than vehicle, but significantly less effective than hydrocortisone 17-butyrate cream in the treatment of atopic dermatitis.

Administration, Topical↗

Ocular findings in atopic dermatitis with special reference to the clinical features of atopic cataract.

44 patients with atopic dermatitis who had had active generalized skin lesions, especially of the face, following transient remission after eczema in infancy were examined ophthalmologically. Their ocular findings have been correlated with the clinical features of atopic dermatitis. 25% of the patients with this clinical course had cataracts. However, the clinical features of the patients without cataracts were almost the same as those of the patients with. Thus, cataracts in patients with atopic dermatitis may not be due to the clinical symptoms and course but to other factors such as genetic, as in the case of asthma. Lenticular opacities were present in the posterior subcapsule in 50%, in the anterior subcapsule in 25% and throughout the lens in 12.5%. 2 patients with total lens opacities had shown rapid progression at the time of exacerbation of the skin lesions. Chronic conjunctivitis was found in 31.8%, superficial keratitis in 6.8% and retinal detachment in 2%.

Adolescent↗

[Inflammatory mediators in patients with atopic dermatitis after treatment with transfer factor].

BACKGROUND: Atopic dermatitis is a skin inflammatory disease, which is associated to high levels of IgE, eosinophiles and change of T lymphocytes. OBJECTIVE: To determine if the treatment with transfer factor for moderate atopic dermatitis decreases the number of inflammatory cells in the peripheral blood. MATERIAL AND METHODS: We selected twenty patients with diagnosis of moderate atopic dermatitis. The age range of the patients was between 5 and 45 years old. Patients were assigned to one of three groups: group A included patients with atopic dermatitis treated with transfer factor: one unit a day for five days, two units a week, one unit a week, one unit every fifteen days and one unit a month. Group B included ten patients with atopic dermatitis who received conventional treatment (hydroxyzine 10 mg/24 h) and the group C was conformed by healthy controls. All patients were submitted to basal and final determination of IgE, peripheral blood eosinophils, and underpopulation of lymphocytes by flow cytometry. Study period was of ten weeks. RESULTS: Levels of IgE were reduced respect to the basal value. In the patients of group A there was an increase in neutrophils and leukocytes after treatment; however, it was not significant (p = 0.46). Eosinophils were significantly reduced (p = 0.01). After comparing group A to group C the p value was of 0.035. CONCLUSION: In patients with atopic dermatitis, after 10 weeks of treatment with transfer factor, the level of IgE and peripheral eosinophils was reduced.

Adolescent↗

Cyclosporin maintenance therapy for severe atopic dermatitis.

Twelve patients with chronic severe atopic dermatitis were treated with cyclosporin A (CsA) in a dose of 5.0 mg/kg/day. All patients except one showed a good therapeutic response. After week six, the CsA dose was reduced until an increased activity of atopic dermatitis was noticed (minimal effective dose). The minimal effective dose fluctuated with the severity of the atopic dermatitis. The mean minimal effective dose was approximately 4.0 mg/kg/day. Maintenance therapy with CsA for atopic dermatitis seems to be effective but may be hampered by side effects in the same way as CsA therapy is hampered by side effects in the treatment of psoriasis.

Adult↗

Role of food allergy in atopic dermatitis.

PURPOSE OF REVIEW: Food allergy and atopic dermatitis often occur in the same patient. Based on clinical data from the past few decades, it is clear that foods such as cow's milk and hen's eggs can directly provoke flares of atopic dermatitis particularly in sensitized infants, whereas inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Because the role and immunology of food allergy in atopic dermatitis remain controversial, here we review data that mainly focus on skin eczema and food allergy. RECENT FINDINGS: Clinical studies have revealed that more than 50% of all children with atopic dermatitis that can be exacerbated by certain foods will react with a worsening of skin eczema alone or in addition to immediate symptoms. Adolescents and adults also react to foods, but reactions to 'classical' food allergens such as hen's eggs and cow's milk are not as common as in childhood. Subgroups of children and of adults with atopic dermatitis do, however, react to pollen-associated foods. Both immunoglobulin E associated and independent T-cell mediated responses appear to be involved in clinical eczematous reactions. SUMMARY: Food-induced eczema should be diagnosed only by a thorough diagnostic procedure, taking into account the patient's history, the degree of sensitization and the clinical relevance of the sensitization. More clinical and immunological studies are needed to unravel the pathophysiology and the different rates of clinical responsiveness to different foodstuffs in patients with atopic dermatitis.

Adolescent↗

Psychosocial factors and adherence to treatment advice in childhood atopic dermatitis.

Poor adherence to maintenance treatment for atopic dermatitis and anxiety about using topical steroids are common features seen among children with atopic dermatitis and their mothers. No systematic study exploring factors associated with adherence to treatment advice on atopic dermatitis has been carried out to date. This study seeks to generate hypotheses regarding the relationship between a range of psychosocial factors and adherence to treatment advice on atopic dermatitis. An anonymous self-completed questionnaire containing adherence items, psychosocial items, some demographic items, and attitudes to steroid use was given to 258 mothers of atopic dermatitis follow-up patients who attended the National Children's Hospital, Tokyo. Responses from 205 families (80%) with complete data were then analyzed to explore the correlation between each factor and to build a structure equation model. The strongest predictor of adherence to skin-care treatment was a good doctor-patient (mother) relationship, followed by the severity of the disease as perceived by the mother. Surprisingly, the mother's anxiety about using topical steroids had no significant influence on reported use of topical steroids nor on adherence to skin-care treatment. This may have been overcome by the well-established doctor-patient (mother) relationship. Maternal personality, husband's cooperation, and social support were indirectly correlated with adherence via the doctor-patient relationship. Maternal self-efficacy of treatment was strengthened by good doctor-patient (mother) relationship.

Adolescent↗

Retinal detachment associated with atopic dermatitis.

BACKGROUND: Retinal detachment associated with atopic dermatitis, one of the most common forms of dermatitis in Japan, has markedly increased in Japan in the past 10 years. To clarify pathogenic mechanisms of retinal detachment in such cases, we retrospectively studied clinical characteristics of retinal detachment associated with atopic dermatitis. METHODS: We examined the records of 80 patients (89 eyes) who had retinal detachment associated with atopic dermatitis. The patients were classified into three groups according to lens status: group A, eyes with clear lenses (40 eyes); group B, eyes with cataract (38 eyes), and group C, aphakic or pseudophakic eyes (11 eyes). RESULTS: No significant differences were noted in the ratio of males to females, age distribution, refractive error, or characteristic of retinal detachment among the three groups. The types of retinal breaks, however, were different in eyes with and without lens changes. While atrophic holes were dominant in group A, retinal dialysis was mainly seen in groups B and C. CONCLUSION: These findings suggested that anterior vitreoretinal traction may play an important role in the pathogenesis of retinal breaks in eyes with atopic cataract and that the same pathological process may affect the formation of cataract and tractional retinal breaks in patients with atopic dermatitis.

Adolescent↗

Contact sensitivity in children and adults with atopic dermatitis--a chronological study.

61 atopic dermatitis patients were subjected to a second patch testing 3-15 years (average 7.3 years) after the first contact sensitivity examination. The comparison between the results of the two studies revealed that 26.2% of patients had been sensitive to one or more haptens at the first patch testing and that 24.6% reacted positively at the second. 9 subjects (14.8%) still manifest contact sensitivity, while 6 (9.8%) reversed to positivity and 7 (11.5%) to negativity. The chemicals most frequently involved were nickel sulphate, potassium dichromate, benzoyl peroxide, diphenylguanidine. This study demonstrates that contact reactions are not linked to susceptibility to skin irritants in atopic dermatitis patients and that they tend to increase with time.

Adolescent↗

Autoantibodies in atopic dermatitis.

Recent progress in the autoimmune aspects of atopic dermatitis has clarified that patients with atopic dermatitis develop IgE-class autoantibodies mainly against intracellular proteins. The cloning of cDNAs encoding autoallergens with human expression cDNA libraries and serum IgE from atopic dermatitis patients has unraveled the molecular characteristics of IgE-binding autoantigens. Some patients with atopic dermatitis also have IgG-class autoantibodies, especially anti-nuclear antibodies. One of the nuclear autoantigens was identified as DFS70/transcription coactivator p75. In addition, p80-coilin in nuclear coiled bodies is also targetted. Several lines of evidence suggest that a subset of atopic dermatitis may be associated with an autoimmune response.

Adaptor Proteins, Signal Transducing↗

[How should severe and chronic atopic dermatitis in children be managed?].

Severe atopic dermatitis in children is rare. When prescribing exceptional treatments (because of failure with classical drugs such as topical corticosteroids or topical immunosuppressors), it is important to ensure that the child is not suffering from an atopic dermatitis that has not been handled correctly. This assessment may require short hospitalisation. When the severity and rebellious nature of the atopic dermatitis with regard to routine treatment has been confirmed, exceptional treatment is envisaged. Currently, the treatment that is mastered in children remains cyclosporine, although marketing authorisation has not been granted in this indication. The side effects and notably nephrotoxicity justify the careful prescription of this drug with regular controls, and the opinion of a paediatric nephrologist. Other immunosuppressive treatments such as azathioprine, mycophenolate mofetil or even interferon gamma have rarely been studied in children, nor particularly in adults, and usually only in open studies. Their safe use in children, in the indication of severe atopic dermatitis obviously warrants comparative studies in large cohorts. Phototherapy should not be banned, even in this paediatric population, but modalities should be further defined, taking into account the real practical possibilities of this type of treatment, depending on the patients' age, and with long-term monitoring. Antileucotrienes have not yet sufficiently demonstrated their efficacy. In such severe forms, ideally, there should be the possibility of defining the predictable factors of efficacy and tolerance in each patient (biologically or with in vitro tests) that would optimise the use of these exceptional treatments, or even new molecules, in well targeted indications. The golden rule remains: patience, explanation, education, observation, monitoring and availability.

Azathioprine↗

In vivo formation of prostaglandin E1 and prostaglandin E2 in atopic dermatitis.

Immunological and biochemical alterations in atopic dermatitis have been attributed to a deficient conversion of omega-6 fatty acids (i.e. linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid) to prostaglandin (PG) E1. In patients with atopic dermatitis, however, the formation of PGE1 has not been evaluated so far. We therefore measured plasma concentrations of 15-keto-13,14-dihydro-PGE1, which reflects endogenous PGE1 release, by gas chromatography-mass spectrometry in 31 patients with atopic dermatitis (aged 18-41 years, median 26 years) and in 31 healthy, age- and sex-matched control subjects. In order to exclude a metabolic shift from PGE1 to PGE2, we also measured the plasma levels of 15-keto-13,14-dihydro-PGE2. There was no difference between patients and control subjects with respect to plasma concentrations of 15-keto-13,14-dihydro-PGE1 (3.9-49.6, median 10.3 pg/ml vs. 3.2-80.4, median 8.3 pg/ml, P = 0.22), 15-keto-13,14-dihydro-PGE2 (11.6-201.0, median 24.8 pg/ml vs. 8.6-201.0, median 19.6 pg/ml, P = 0.10), and the ratio of 15-keto-13,14-dihydro-PGE1 to 15-keto-13,14-dihydro-PGE2 (0.17-1.39, median 0.41 vs. 0.2-1.17, median 0.45, P = 0.29). These results indicate that the endogenous formation of both PGE1 and PGE2 is normal in our patients. The results do not confirm the pivotal role that other authors have attributed to a deficient PGE1 formation in the pathogenesis of atopic dermatitis.

Adolescent↗

Comparative proteomic analysis of peripheral blood eosinophils from healthy donors and atopic dermatitis patients with eosinophilia.

Atopic dermatitis (AD) is an allergic disease that has recently shown a dramatic increase of incidence in developed countries. Eosinophilia, the accumulation of eosinophils, occurs in AD patients through an anti-apoptotic mechanism. To understand the target proteins involved in the anti-apoptotic signaling of eosinophilia, we used a proteomic approach to analyze eosinophil proteins from AD patients with eosinophilia and healthy donors. Protein spots in two-dimensional electrophoresis (2-DE) gels were identified with peptide mass fingerprinting (PMF) based on matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and database searching. More spots were observed in the 2-DE proteome map from AD patient samples (1310 +/- 58 spots) than in those from healthy donors (1121 +/- 40 spots). We identified 51 proteins affected by eosinophilia: 19 related to signaling, 8 involved in regulation of metabolism, 4 related to apoptosis, and 3 involved in inflammation. The other identified proteins were associated with transcription, RNA processing, translation, the cytoskeleton, and unknown functions. Among the identified proteins, we observed prominent increases in the expressions of cyclinA2, voltage-dependent anion channel protein 2, and 38 kDa FK506 binding protein 8 in eosinophils from AD patients in comparison to healthy donors. PMF and immunoblotting of a single spot that was expressed in eosinophils from healthy individuals but not in AD patients identified the protein as phosphorylated growth receptor binding 7 (Grb7) adaptor protein. Increased phosphorylation of Grb7 and its upstream signaling protein, focal adhesion kinase (FAK), was detected in low viability eosinophils such as those from healthy donors or in cultured eosinophils (AML14.3D10 cells) treated with dexamethasone. These results suggest that phosphorylation of Grb7 and the expressions of cyclinA2, voltage-dependent anion channel protein 2, and 38 kDa FK506 binding protein 8 may be related with the anti-apoptosis mechanism of eosinophilia.

Apoptosis↗

[Atopic dermatitis and psychological stress].

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Its main features are eczematous skin lesions with a typical distribution and severe pruritus. Allergens, skin irritants, systemic or local infections, environmental pollutants and hormonal changes have a role in the pathophysiology of AD. A further important trigger factor for both intrinsic and extrinsic AD is emotional stress. Recently published observations point to direct psychoneuroimmunological and -endocrinological mechanisms: Psychological stress causes a transient increase of peripheral blood eosinophil count and an increase in both CD8+/CD11b+ and CLA+ T-cells. In addition, stress changes the cytokine and the hormone profile with increased levels of IFN-gamma and IL-5, and decreased levels of cortisol in AD patients in contrast to healthy controls. These findings underline the role of immunological changes and a possible suppressed hypothalamic-pituitary-adrenal (HPA) axis closing the loop for the final aggravation of AD.

Adult↗

Lessons from atopy patch testing in atopic dermatitis.

The exposure of atopic eczema (AE) patients to their relevant protein allergens (eg, from house dust mite, cat dander, grass pollen, or food allergens) can trigger an exacerbation or maintain the disease. Diagnostic procedures are needed to specify allergen avoidance recommendations for the individual patient. Skin prick tests and specific serum IgE tests might be helpful in pointing out potential trigger factors, but relevance needs to be confirmed (eg, with food provocation tests). The atopy patch test (APT) involves the epicutaneous application of intact protein allergens in a diagnostic patch test setting with an evaluation of the induced eczematous skin lesions after 24 to 72 hours. The APT targets the cellular component of AE and helps round out the AE test spectrum. As a number of apparently minor test modifications greatly influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique. It consists of purified allergen preparations in petrolatum, applied in 12-mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin of the upper back. The APT is read at 48 and 72 hours according to the test criteria and reading key of the ETFAD for appearance of erythema, and number and distribution pattern of the papules. In contrast with skin prick tests, the APT might even detect a relevant sensitization in the absence of specific IgE. Many studies have been undertaken to objectify the sensitivity and specificity of the APT to show its diagnostic use in clinical practice.

Advisory Committees↗

Topical treatment of atopic dermatitis.

Topical therapy of atopic dermatitis should incorporate an understanding of the underlying immune abnormalities of this complex chronic skin disease. Avoidance of irritants and proven allergens, skin hydration, and use of emollients and anti-inflammatory therapy help maintain a normal skin barrier. Topical calcineurin inhibitors have been added to the topical treatment armamentarium. Although the optimal treatment approach remains to be defined, several studies suggest the use of topical calcineurin inhibitors as early intervention therapy and topical corticosteroids as rescue therapy.

Administration, Topical↗

Adult-onset atopic dermatitis.

Adult-onset atopic dermatitis (AD) is a recently introduced subgroup of AD. Apart from the most typical flexural lichenified/exudative pattern in adults, patients may also have nontypical morphology and localization. The aim of this retrospective study was to find the frequency of nontypical morphology and localization in adult-onset AD and to evaluate the accuracy of United Kingdom Working Party's criteria in detecting those cases. Among 376 patients consecutively diagnosed with AD according to criteria of a previous study, 63 patients (34 women and 29 men) (16.8%) with onset of AD after the age of 18 years were allocated to the adult-onset group. A total of 7 patients (11.1%) had nonflexural involvement with nummular (6.3%), prurigo-like (3.2%), or follicular (1.6%) patterns that could not be attributed to contact sensitivities. A total of 14 patients (22.2%) did not fulfill the United Kingdom Working Party's criteria. It was interesting that United Kingdom Working Party's criteria did not cover the same patients as did the previous study's criteria in nearly one fourth of the cases.

Adult↗

Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are common inflammatory skin diseases. Although many reports implicate Th2 cytokines in the pathophysiology of AD and Th1 cytokines in psoriasis, the precise etiology of these diseases remains elusive. OBJECTIVE: We investigated novel AD- or psoriasis-related genes to further understand the pathogenesis of these diseases. METHODS: We performed a comprehensive analysis of mRNA expression in skin biopsies from AD or psoriasis patients using DNA microarrays. Quantitative PCR was then used to monitor the expression of novel disease-related genes in human keratinocytes or pinnae from NC/Nga mice. RESULTS: Levels of mRNA for IDO (indoleamine 2,3-dioxygenase) and kynureninase, enzymes constituting the tryptophan degradation pathway, were found to be upregulated in the skin lesions as compared to the uninvolved skin of patients with AD or psoriasis. Expression of these two genes was induced in human epidermal keratinocytes stimulated with IFN-gamma in vitro. Moreover, in NC/Nga mice, the expression of kynureninase mRNA in the ear skin was induced following development of AD-like skin lesions. CONCLUSION: The tryptophan degradation pathway may play an important role in the pathophysiology of AD and psoriasis.

Adult↗

In vivo expression of IL-12 and IL-13 in atopic dermatitis.

Previous studies in atopic dermatitis (AD) have shown that acute and chronic skin lesions are associated with a TH2-type profile of cytokine expression. IL-12 and IL-13 are recently described cytokines, which possess TH1-and TH2-like actions, respectively. We have used the technique of in situ hybridization to examine the expression of IL-12 and IL-13 messenger RNA in skin biopsy specimens of acute and chronic skin lesions and uninvolved skin from patients with AD. When compared with normal control skin, the acute and chronic skin lesions and unaffected skin from patients with AD had significantly greater numbers of cells that were positive for IL-13 mRNA (p < 0.05). Acute AD skin lesions expressed a higher number of positive cells than those observed in chronic AD skin lesions (p < 0.05) or psoriasis skin lesions (p < 0.05) There was a significant increase in the numbers of IL-12 mRNA-positive cells in chronic skin lesions compared with acute lesions and uninvolved skin from patients with AD (p < 0.05). These data demonstrate that acute AD skin lesions are associated with an increased expression of IL-13 mRNA. In contrast, the relative increase in IL-12 mRNA in chronic AD skin lesions suggests a possible role for IL-12-producing cells in modulating chronic inflammation.

Acute Disease↗