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PubMed2002

Topical tacrolimus: a new therapy for atopic dermatitis.

Atopic dermatitis is a common problem affecting up to 10 percent of all children. The mainstays of therapy have been oral antihistamines, topical emollients, topical doxepin, and topical corticosteroids. Side effects associated with higher potency topical corticosteroids have limited their use in children and for facial areas. Tacrolimus (Protopic) is an immunosuppressive agent typically used systemically in transplant patients. Used topically, it has been found to be effective in treating moderate to severe atopic dermatitis without causing the atrophy that might occur with prolonged use of topical corticosteroids. Tacrolimus works equally well in children and adults, with more than two thirds of both groups having an improvement of greater than 50 percent. Despite its potency, very little of the medication is systemically absorbed, and absorption decreases as the atopic dermatitis resolves. The main side effects are burning and itching, but these also decrease with improvement of the atopic dermatitis.

Administration, Cutaneous↗

PubMed2002

A review of high-dose intravenous immunoglobulin treatment for atopic dermatitis.

Atopic dermatitis generally responds to topical therapy; however, small numbers of patients have severe resistant disease despite second line therapies. High-dose intravenous immunoglobulin (HdIVIg) which is being used increasingly for dermatological indications has been suggested to be of benefit in a small number of uncontrolled trials and case reports. The mode of action is via a number of immunomodulatory mechanisms and it is not associated with the many side-effects of steroids and other immunosuppressive agents. There are now reports of 32 atopic dermatitis patients treated with HdIVIg, and this review aims to make a critical assessment of the current data. These have been obtained from a Medline search of the English literature from 1966 to 2001 for intravenous immunoglobulin and atopic dermatitis/eczema. Taken together an improvement was observed in 61% of atopic dermatitis patients treated with HdIVIg. Adults appeared less likely to respond (48%) than children (90%) and the duration of response was also more prolonged in children. Adjunctive therapy in adults was more effective than monotherapy (59% vs 0%), whereas monotherapy was effective in 90% of children. HdIVIg may offer a safe potential therapeutic avenue for resistant cases of atopic dermatitis, particularly in children, but should be further assessed using double-blind placebo-controlled trials.

Adult↗

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↗

PubMed1989

Recent investigations on the relationship between fungal skin diseases and atopic dermatitis.

Atopic dermatitis may be associated with chronic dermatophyte infections and Pityrosporum related disorders. Recent epidemiologic studies in school children and young recruits have confirmed that atopic individuals have an increased susceptibility to Trichophyton rubrum infections of the feet and an increased risk for persistent infections. In contrast, an investigation on skin reactivity in dermatophyte infected atopic patients indicated that a group of these patients is fully able to eliminate the fungi concomitant with the development of a delayed type skin reactivity. Facial erythema and scaling, often including neck and shoulders, is present in many young adults with atopic dermatitis. Preliminary data from a Danish-Swedish investigation have shown that atopic dermatitis patients with head-neck-shoulder dermatitis compared to a group without this disorder and normal individuals more often demonstrate positive prick test, RAST and specific histamine release using extract of Pityrosporum ovale. These findings indicate that the presence of Pityrosporum ovale in the skin may cause an allergic reaction leading to dermatitis.

Arthrodermataceae↗

PubMed2000

Systemic therapy of atopic dermatitis.

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease. Topical therapy is the mainstay, but patients with widespread moderate to severe atopic dermatitis may require systemic therapy. Immunosuppressants, immune response modifiers, antihistamines and antibiotics are among the classes of systemic medications frequently used to treat extensive atopic dermatitis; the indications and scientific support for the use of these and other less commonly used medications will be reviewed in this article.

Anti-Allergic Agents↗

PubMed1983

Staphylococcus aureus and atopic dermatitis.

Atopic dermatitis is a genetically determined skin disease that is strongly influenced by environmental factors. The skin of affected patients is usually colonized by large numbers of Staphylococcus aureus bacteria. These bacteria may aggravate atopic dermatitis or prevent resolution of the disease. The deleterious effects of S aureus on atopic dermatitis may be due to direct biologic action or may be due to indirect damage mediated by the immune and inflammatory systems.

Antigens, Bacterial↗

PubMed2004

New insights into atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.

Dermatitis, Atopic↗

PubMedDate not supplied

[Immunomodulation by tacrolimus in atopic dermatitis].

Atopic dermatitis is a common allergic disease, in which the treatment is extremely complex; even when several immunological abnormalities have been described in atopic dermatitis, the immune response to drugs remains unclear for both: conventional and unconventional therapies. The present review is centered on clinical efficacy and safety of tacrolimus, one of the immunomodulators proposed to treat atopic dermatitis. There are clinical evidences to support that tacrolimus have considerable impact on expression of inflammatory markers, despite of clinical assays could be necessary to demonstrate its profiles of toxicity and efficacy, during long-time periods.

Calcineurin Inhibitors↗

PubMedDate not supplied

Cyclosporine A in atopic dermatitis.

Atopic dermatitis is a chronic pruritic dermatosis that requires individualized treatment. Recent studies have shown that low-dose oral treatment with cyclosporine A may be useful in more severe forms. We report our experience with two patients who had severe atopic dermatitis. Both had high IgE concentration and satisfied Hanifin and Rajka's diagnostic criteria for atopic dermatosis. We began oral treatment at a daily dosage of 5 mg/kg divided into two doses. We monitored cyclosporine concentration in whole blood, as well as kidney and liver function. Contraindications for cyclosporine A were excluded. Clinical improvement commenced between the first and third week of treatment and was marked in one case and partial in the other. Improvement did not correlate with a reduction in serum IgE concentration. Side effects were mild (hypertrichosis, slight trembling, and gingival hypertrophy). On discontinuing treatment, clinical manifestations reappeared. We conclude that cyclosporine A may be an effective alternative for some forms of atopic dermatitis resistant to other treatments.

Adult↗

PubMed1998

Atopic dermatitis.

Atopic dermatitis is the most common skin disease of childhood, and its prevalence has steadily increased over the last three decades. A chronic, relapsing condition, atopic dermatitis has a significant impact on affected children, their families, and the community at large. Although the fundamental pathogenesis has remained elusive, intensive research has greatly contributed to our understanding of this disease. As the specific immunobiologic pathways become deciphered, we have seen the propagation of several new therapeutic options that rationally attack specific underlying immune system abnormalities. This article highlights the specific contributions made to the literature over the past year, with particular attention to the immunopathogenesis of atopic dermatitis, as well as some new targeted therapies currently and soon to be available.

Administration, Topical↗

PubMed2001

Pathophysiologic mechanisms in atopic dermatitis.

Atopic dermatitis is a common, chronic inflammatory skin disease that frequently predates the development of asthma and/or allergic rhinoconjunctivitis. Recent studies have provided new insights into how the complex interrelationship of genetic, environmental, and immunologic factors may contribute to the development of atopic dermatitis. This article examines some of the factors involved in chronic cutaneous inflammation in this disease. Greater understanding of the mechanisms that underlie the pathophysiology of atopic dermatitis may lead to improved treatment strategies for this increasingly common skin disease.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Pharmacoeconomics of drug therapy for atopic dermatitis.

Atopic dermatitis is an increasingly prevalent common childhood disease. While the majority of patients have mild disease, atopic dermatitis can cause considerable distress to patients and their caregivers, with significant social and financial cost to families. With a prevalence of 15 - 20% in Western countries, atopic dermatitis also has a considerable health and societal cost to the community. Many new treatments have been shown to be therapeutically effective, particularly in severe disease, including cyclosporin A (Neoral, Novartis AG), interferon, tacrolimus (Fujisawa Pharmaceutical Co. Ltd.) and iv. immunoglobulin. These are expensive when compared to standard treatments like emollients and topical corticosteroids and have significant adverse effects that limit their use. Additional costs related to monitoring are incurred and the long-term safety of these treatments is yet to be determined. However, an advantage over more traditional therapies is their ability to produce benefits even after treatment ceases. Treatments that produce long-term remissions have a greater likelihood of being cost-effective. With monetary constraints on healthcare and the importance governments place on reducing drug costs, economic evaluations are becoming an increasingly important factor for drug acceptance. Those evaluating cost-effectiveness should pay particular attention to the potential reduction in indirect and intangible costs. Unfortunately, there is a dearth of cost-effectiveness studies in atopic eczema and this needs to be addressed with some urgency.

Cost of Illness↗

PubMedDate not supplied

The psychosocial burden of childhood atopic dermatitis.

Atopic dermatitis is an extremely common childhood disease of increasing prevalence that greatly affects the quality of life of afflicted children and of their families. The disease alters the emotional and social functioning of the affected child and their family. The complex multidimensional effects of atopic dermatitis in children and families have been described qualitatively and measured quantitatively with quality of life instruments. Emotional effects on both the child and parents are predominant. The burden of atopic dermatitis can be improved by targeting parents and caregivers with education, psychosocial support, and specialty care.

Child↗

PubMed1991

[Pathogenesis of atopic dermatitis].

Atopic dermatitis shows a familial disposition and is characterised clinically by extreme pruritus, typical eczematoid pathology and distribution on the integument, a chronic relapsing course, and a personal or familial history of atopic diseases (allergic bronchial asthma, rhinitis and allergic conjunctivitis, atopic dermatitis), as well as numerous other stigmata and microsymptoms. Although numerous exogenous factors help trigger the disease, more recent findings point to an immunological basis. In recent years, numerous cellular malfunctions of immune cells have been reported, with disturbances in T-lymphocyte predominating. The latest investigations now suggest that the reported changes in the immune response are due to an imbalance in the cytokine network. Thus, it has been observed that disturbances of cytokine production depend upon the severity of the disease, and show an AD-characteristic pattern. The pathogenesis of atopic dermatitis however, is not yet fully understood.

Dermatitis, Atopic↗

PubMed2005

[Inpatient rehabilitation of chronic dermatoses illustrated by atopic dermatitis].

Atopic dermatitis is defined as a chronically relapsing skin disease resulting from complex interactions between genetic and environmental factors. It usually occurs during early childhood and shows typical clinical manifestations, depending on the patient's age. In cases of chronic atopic dermatitis, negative effects on professional and social activities and participation have to be expected. To counteract or overcome these threatening impairments in the different facets of life, prescribing inpatient rehabilitative measures should be considered early. Dermatological rehabilitation according to guidelines guarantees an interdisciplinary and multimodal treatment of atopic dermatitis.

Chronic Disease↗

PubMed1995

Elevation of serum-soluble E-selectin in atopic dermatitis.

Atopic dermatitis (AD) is characterized by alterations in cellular and humoral immunity. The objective of this study is to determine whether soluble E-selectin (sE-selectin) plays a role in AD. We examined the serum sE-selectin levels in patients with atopic dermatitis (n = 23), patients with urticaria (n = 9), and normal healthy individuals (n = 15). The severity of the disease in the AD patients was graded using an established clinical scoring system. We found that sE-selectin levels were significantly higher in atopic dermatitis than in urticaria (P < 0.001) or normal controls (P < 0.0001). In addition, there was a significant correlation between serum sE-selectin and the clinical score (R = 0.73, P < 0.0001). Clinical improvement was associated with a decrease in both the clinical score (P < 0.01) and serum sE-selectin (P < 0.01). E-selectin was recognized on the vascular endothelial cells of the erythematous lesions of AD patients. These results indicate that sE-selectin may play a role in AD.

Adolescent↗

PubMed2003

Atopic dermatitis.

Atopic dermatitis is a common, chronic skin condition characterized by xerosis, pruritus, and inflammation. Numerous factors place individuals at increased risk for developing this disease. T-helper cells and their cytokines, in addition to immunoglobulin E and eosinophils, play a major role in the pathogenesis of atopic dermatitis. Various hypotheses including the "hygiene hypothesis" and the "keratinocyte apoptosis hypothesis" have been proposed. Diagnosis is based on clinical criteria rather than objective testing. Allergic reactions to several triggers including foods may exacerbate symptoms. Treatment for atopic dermatitis consists of avoidance of triggers and administration of emollients, steroids, and topical immune response modifiers such as tacrolimus. Further research is necessary to better understand this disease.

Administration, Topical↗

PubMed2006

Recent developments in the treatment of adult atopic dermatitis.

Atopic dermatitis is a common inflammatory skin condition with increasing incidence in recent decades. The mainstay of treatment has been the combination of emollients and topical corticosteroids, with the addition of systemic therapies in severe cases. New drugs such as the topical calcineurin inhibitors have shown promise in treating mild-to-severe atopic dermatitis. Other novel therapies that have been reported in the literature include leukotriene antagonists, monoclonal antibodies such as infliximab, leflunomide, recombinant interferon gamma and intravenous immunoglobulin. This review will focus on the treatment of adult atopic dermatitis.

Antibodies, Monoclonal↗