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PubMed2007

Early cutaneous gene transcription changes in adult atopic dermatitis and potential clinical implications.

Atopic dermatitis (AD) is a common pruritic dermatitis with macroscopically non-lesional skin that is often abnormal. Therefore, we used high-density oligonucleotide arrays to identify cutaneous gene transcription changes associated with early AD inflammation as potential disease control targets. Skin biopsy specimens analysed included normal skin from five healthy non-atopic adults and both minimally lesional skin and nearby or contralateral non-lesional skin from six adult AD patients. Data were analysed on an individual gene basis and to identify biologically relevant gene networks. Transcription levels of selected genes were also analysed by quantitative PCR. Differential transcription occurring early in AD skin was indicated for (i) individual genes such as C-C chemokine ligand (CCL)18, CCL13, and interferon-alpha2 (IFNalpha2), (ii) genes associated with peroxisome proliferator-activated receptor (PPAR)alpha- and PPARgamma-regulated transcription, and possibly for (iii) immunoglobulin J-chain and heavy chain isotype transcripts. These data suggest that local changes in immunoglobulin-associated transcription may favour IgE over secretory immunoglobulin (multimeric IgM and IgA) expression in AD skin. Decreased PPAR activity appears common to both AD and psoriasis, and reduced cutaneous IFNalpha2 transcription also appears characteristic of AD. Identification of these genes and pathways will direct future research towards controlling AD.

Adult↗

PubMed1993

Mitosis of mast cells in skin lesions of atopic dermatitis.

Mitoses of mast cells with cytoplasmic granules were observed in 6 out of 55 skin lesions of atopic dermatitis. It is thus likely that the local proliferation process of mast cells contributes to the increased number of mast cells in skin lesions of atopic dermatitis. Mitotic mast cells with cytoplasmic granules were also observed in 2 out of 8 dinitrochlorobenzene contact dermatitis lesions provoked in patients with atopic dermatitis. It is suggested that some mast cells in skin lesions of atopic dermatitis might be involved in the pathogenesis of type IV eczematous skin lesions of the disease.

Adolescent↗

PubMed2002

Spotlight on topical pimecrolimus in atopic dermatitis.

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.

Administration, Topical↗

PubMed2002

Topical pimecrolimus: a review of its clinical potential in the management of atopic dermatitis.

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and paediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus 1.0% cream has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Pimecrolimus 1.0% cream provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.

Administration, Cutaneous↗

PubMed1990

Thymopentin therapy reduces the clinical severity of atopic dermatitis.

One hundred patients with moderate to severe atopic dermatitis were entered into a two-center, double-blind trial. Patients were randomized to receive either thymopentin (Timunox, n = 48) or placebo (n = 52), administered as daily subcutaneous injections for 6 weeks. Clinical extent of disease and severity parameters were measured at baseline and at regular time intervals during the study. Both the placebo- and thymopentin-treated groups demonstrated a progressive and statistically significant (p less than 0.001) decline in the overall severity of their disease, but reduction in the clinical severity score was higher in the thymopentin-treated group and statistically significant (p = 0.04) in comparison with the placebo-treated group after 6 weeks of treatment. Of the individual symptoms comprising the total severity score, pruritus (p = 0.02) and erythema (p = 0.04) were reduced significantly when thymopentin therapy was compared to placebo therapy. In addition, both the extent of body involvement and severity index (a combined severity/extent index) were significantly reduced after 6 weeks in the thymopentin-treated group in comparison to the placebo-treated group (p = 0.04). There were no serious adverse experiences in either treatment group. We conclude that treatment with thymopentin is safe and offers significant therapeutic promise for atopic dermatitis.

Adolescent↗

PubMed2001

Nonclinical and early clinical development of tacrolimus ointment for the treatment of atopic dermatitis.

Tacrolimus ointment, formulated for the treatment of atopic dermatitis, is the first in a class of topical immunomodulators. Its mechanism of action is based on calcineurin inhibition, which results in suppression of antigen-specific T-cell activation and inhibition of inflammatory cytokine release. Animal and human studies have shown that topically applied tacrolimus is minimally absorbed into the systemic circulation, the fraction that is absorbed is extensively distributed, and tacrolimus does not accumulate in tissues following repeated topical application. In addition, tacrolimus ointment is not inherently irritating, sensitizing, phototoxic, or photoallergenic when applied to intact skin. Unlike some topical corticosteroids, tacrolimus ointment does not cause a decrease in collagen synthesis or skin thickness, nor does it produce skin abnormalities or depigmentation. In animal studies, repeated daily application of tacrolimus ointment up to 1 year is associated with dermal findings similar to those following vehicle application (mild to moderate dermal irritation and microscopic findings of acanthosis, hyperkeratosis, and superficial inflammation). In a 52-week study with Yucatan micropigs, no noteworthy macroscopic or microscopic changes (either dermal or systemic) related to the application of tacrolimus ointment (0.03% to 0.3% concentrations) were observed. Tacrolimus ointment was shown to be safe and effective in phase 2 and early phase 3 studies. Significant improvements in atopic dermatitis were observed in the majority of patients treated with tacrolimus ointment. The most common adverse events associated with its use were a transient burning sensation and pruritus at the site of application. Blood tacrolimus concentrations were below the limit of quantitation in most patients.

Animals↗

PubMed1997

Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis.

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4), CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 nor CD80 was detected on keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n = 7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n = 8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely inhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.

Animals↗

PubMed1992

Management of severe atopic dermatitis.

The lack of knowledge concerning the pathophysiology of atopic dermatitis (AD) explains the absence of any specific treatment specially in severe atopic dermatitis. New treatments were recently suggested for the management of the disease. They all act on some component of the immune mechanisms which provoke the eczematous reactions. Among recent treatments proposed, I will discuss the use of cyclosporin A, puva therapy, thymopoietin and thymostimulin, antifungal therapy, alpha and gamma interferon, and treatment with interleukin 2.

Cyclosporine↗

PubMed2006

Treatment of atopic dermatitis with the xenon chloride excimer laser.

BACKGROUND: Narrow-band ultraviolet B phototherapy is an effictive and safe treatment for atopic dermatitis. We have previously found that the 308 nm xenon chloride excimer laser was more effective than the narrow-band ultraviolet B light for the treatment of psoriasis, suggesting that ultraviolet B laser might offer advantages over narrow-band ultraviolet B. OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy of the 308 nm excimer laser in atopic dermatitis. PATIENTS AND METHODS: Fifteen patients with atopic dermatitis (less than 20% body area involvement) were treated with a xenon chloride excimer laser (XTRAC laser, Photomedex Inc.) twice weekly. The severity of the atopic dermatitis was assessed via (i) a clinical score characterizing the intensity of erythema, infiltration, lichenification and excoriation; (ii) the quality of life, determined by means of a questionnaire; and (iii) a visual linear analogue scale, with which the patients scored the severity of their pruritus. RESULTS: After 1 month of laser therapy, the clinical scores were significantly lower than the initial values. Similar decreases were observed for the quality of life and pruritus scores. No serious or unpleasant side-effects were observed. CONCLUSION: These results suggest that the xenon chloride excimer laser is an effective and well-tolerated treatment for localized atopic dermatitis.

Adolescent↗

PubMed2004

Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis.

BACKGROUND: Although both interleukin-4 (IL-4) and IL-13 induce immunoglobulin E (IgE) production in vitro, the relative contribution of the two cytokines in various skin lesions of atopic dermatitis remains unclear. OBJECTIVE: We examined the relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis for IgE production. METHODS: The study group comprised 28 atopic dermatitis patients with serum IgE levels more than 2000 IU/ml. The expression levels of IL-4 mRNA and IL-13 mRNA versus that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) method in samples of normal-appearing skin from seven patients, very mild lesions from eight patients, subacute lesions from ten patients and lichenified lesions from ten patients with atopic dermatitis, and in samples of normal skin from six healthy control subjects. RESULTS: IL-4 mRNA expression was identified in only two of the eight very mild lesions, one of the ten subacute lesions, and none of the ten lichenified lesions, whereas IL-13 mRNA expression was identified in 27 of the 28 skin lesions of atopic dermatitis. The IL-13 mRNA/GAPDH mRNA ratios (x100) in the subacute lesions (94.4+/-20.6) and lichenified lesions (71.4+/-40.4) were significantly greater than in the skin of healthy controls (13.1+/-17.7; P<0.01, P<0.05, respectively). CONCLUSIONS: Upregulation of IL-13 mRNA in subacute and chronic lesions of atopic dermatitis along with scant expression of IL-4 mRNA suggest that IL-13 is a crucial cytokine in lesional skin.

Adult↗

PubMed2004

Malassezia sympodialis stimulation differently affects gene expression in dendritic cells from atopic dermatitis patients and healthy individuals.

It is known that 28-84% of patients with atopic dermatitis exhibit IgE and/or T-cell reactivity to the opportunistic yeast Malassezia sympodialis, which can be taken up by immature monocyte-derived dendritic cells (MDDCs), resulting in MDDC maturation. The aim of this study was to investigate whether MDDCs from patients with atopic dermatitis respond differently to M. sympodialis compared to MDDCs from healthy individuals. Immature MDDCs were stimulated with M. sympodialis and the gene expression profiles were analysed with cDNA arrays containing 406 genes. Our results show that M. sympodialis differently affected MDDCs from patients with atopic dermatitis, and more so in severely ill patients, compared with healthy individuals. Six genes were more than fivefold up-regulated in MDDCs from more than one patient with atopic dermatitis, coding for CD54, CD83, IL-8, monocyte-derived chemokine (MDC), BTG1 and IL-1R antagonist. In healthy individuals this was true only for BTG1. Up-regulations of IL-8 and MDC were confirmed at the protein level. Our findings might reflect an increased trafficking and stimulatory capacity in MDDCs from the patients, which is likely to result in a stronger inflammatory response to M. sympodialis.

Adult↗

PubMedDate not supplied

Different lymphocyte markers and cytokine expression in peripheral blood mononuclear cells in children with acute atopic dermatitis.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) is still not completely understood. AD is characterized by the presence of clinical symptoms of both IgE antibody-mediated immediate hypersensitivity and specific T lymphocyte-mediated delayed hypersensitivity. OBJECTIVE: To evaluate the immunological mechanisms involved in children with acute AD lesions. MATERIAL AND METHODS: Ten children with acute AD lesions and 10 non-atopic controls were studied. Total IgE was measured by immunoassay. T cell marker expression (CD3, CD4, CD8, cutaneous lymphocyte-associated antigen [CLA]) and cytokine production (interferon [IFN]-gamma, interleukin [IL]-13) were analyzed in peripheral blood mononuclear cells by flow cytometry. RESULTS: In children with AD the percentage of CD3+ cells (p = 0.015) increased while that of CD8+ cells (p = 0.023) decreased, with no differences in CLA expression. We found increased IL-13 production in CD3+ cells (p = 0.01) and CD3+CD4+ (p = 0.001) cells with no difference in IFN-gamma. Total IgE was significantly higher in patients with AD (p = 0.01). Comparison of IL-13 production in CD4+ cells categorized by total IgE level showed that IL-13 production was significantly increased in subjects with a higher IgE level. CONCLUSION: Peripheral blood from children with AD showed an increase in IgE levels and a Th2 pattern. There was a correlation between IL-13 production and total IgE levels.

Antigens, CD↗

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↗

PubMed2003

Fluocinolone acetonide 0.01% in peanut oil: therapy for childhood atopic dermatitis, even in patients who are peanut sensitive.

BACKGROUND: Fluocinolone acetonide 0.01% in a blend of refined peanut and mineral oils has been used as treatment for scalp psoriasis for several years, but only more recently for atopic dermatitis. OBJECTIVE: We sought to study the effectiveness for atopic dermatitis, potential for adrenal axis suppression, and safety of the fluocinolone acetonide 0.01% in oil in children with atopic dermatitis, including children with atopic dermatitis and peanut allergic sensitivity. METHODS: Three separate studies were performed in children aged 2 to 12 years with atopic dermatitis: multicenter double-blind, randomized, and vehicle-controlled trial; cortisol stimulation testing; and prick testing, patch testing, and monitored medication use in children with peanut allergic sensitivity. RESULTS: Improvement of >/=50% was demonstrated within 2 weeks in 81% to 87% of 81 patients treated with active medication versus 39% of 45 children treated with vehicle oil alone. No adrenal suppression occurred after 4 weeks of therapy in 32 patients. None of 9 patients who were peanut sensitive reacted to either the full formulation or vehicle in prick or patch testing; 20 children who were peanut sensitive showed no allergic reactions after application of the medication. CONCLUSION: Fluocinolone 0.01% in peanut oil is an effective alternative to the use of topical corticosteroid agents in ointment, cream, and lotion forms in children. No evidence of adrenal suppression or adverse local effects were demonstrated in these studies. The medication was well tolerated in patients with peanut allergic sensitivity.

Administration, Topical↗

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↗

PubMed2003

IgE and IgG antibodies to Malassezia spp. yeast extract in patients with atopic dermatitis.

The presence of immunoglobulins to Malassezia spp. surface proteins in the sera from patients with atopic dermatitis and healthy subjects was studied. It was found that 28% of 25 examined patients with atopic dermatitis had IgE antibodies to Malassezia spp. surface protein preparation. All patients and 5 healthy subjects had IgG antibodies to this preparation. The presence and concentration of specific IgE antibodies in patients with atopic dermatitis correlated with reverse titers of IgG antibodies to this preparation (r=0.782). The medians of values reciprocal to IgG antibody titers in patients with atopic dermatitis with and without specific IgE antibodies to the preparation and in healthy subjects were 64, 1024, and 16, respectively. The preparation derived from Candida albicans (candidine) and previously derived preparation from Malassezia did not cross-react. According to immunoblotting data, the preparation contains allergens presented by proteins with molecular weights 15, 36, 52-56, and 78.4 kDa.

Adolescent↗

PubMed1992

Interleukin-2 production of lymphocytes in food sensitive atopic dermatitis.

The proliferative responses of peripheral blood mononuclear cells (PBMC) to food antigens in 22 patients with food sensitive atopic dermatitis were significantly higher than the responses of healthy children and food sensitive children with immediate symptoms. Moreover, the activity of interleukin-2 (IL-2) in supernatants of food antigen stimulated PBMC cultures from patients with atopic dermatitis was significantly higher than that in healthy children and food sensitive children with immediate symptoms. The activity of IL-2 in culture supernatants of separated cell populations stimulated with food antigens from patients with atopic dermatitis and healthy children was investigated. The activity of IL-2 in supernatants of food antigen stimulated T cell cultures could be detected in patients with atopic dermatitis but not in healthy children. These results suggest that the increased IL-2 production after food antigen stimulation is due to increased T cell activity in food sensitive atopic dermatitis.

B-Lymphocytes↗

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↗