Filaggrin null mutations in childhood atopic dermatitis among the Chinese

Atopic dermatitis (AD) is associated with loss or reduced expression of filaggrin (FLG). We evaluated five FLG null mutations, namely R501X, 2282del4, R2447X, S2554X, and S2889X, in 174 Chinese children with AD and 191 matched controls. 2282del4, R2447X, S2554X and S2889X mutations were not found in these patients. Heterozygous carriage of R501X was only found in four male patients, and associated with long‐term disease severity. FLG mutations prevalent in Caucasian and other Asian populations are rarely found in our series.     

Milk allergy/intolerance and atopic dermatitis in infancy and childhood

Adverse reactions to cow's milk proteins are usually indicated as cow's milk allergy/intolerance (CMPA/CMPI) because no differentiation is possible on the basis of symptoms, and there is no reliable single laboratory test available for the diagnosis of CMPA or CMPI. Elimination and challenge tests for cow's milk proteins using strict, well-defined diagnostic criteria are required for the diagnosis of CMPA/CMPI. Atopic dermatitis (AD) is one of the most common symptoms of CMPA/CMPI. Approximately one third of AD children have a diagnosis of CMPA/CMPI according to elimination diet and challenge tests, and about 40–50% of children <1 year of age with CMPA/CMPI have AD. Many children with AD and CMPA/CMPI develop a complete tolerance to CMP in a few years. Children with persisting forms of CMPA/CMPI have a more frequent history of familial atopic disease, change in CMPA/CMPI manifestations over time and very high frequency of multiple food intolerance and allergic diseases. Many children who outgrow their AD develop other allergic diseases, such as rhinitis or asthma. The simultaneous development of allergic tolerance in one organ and the intolerance or atopic disease in another organ suggest that genetic, immunologic and environmental factors play a complex role in the natural history of AD and other atopic diseases.     

Dietary treatment of childhood atopic eczema/dermatitis syndrome (AEDS)

Objective:  This review summarizes the research and clinical evidence in favour of dietary intervention aimed at eliminating allergenic foods in the management of atopic eczema/dermatitis syndrome (AEDS).
Data sources:  The data source was PubMed, using a search algorithm selecting for clinical studies of AEDS, diet therapy and food allergy in all children to October 2003. Also included is a commentary based on the authors' clinical experience in the allergy unit of a university hospital in Italy.
Results:  Fourteen prospective studies matched the entry criteria. Diverse trial designs, diagnostic criteria, types of dietary intervention and length of observation periods precluded meta-analytic methods. Allergenic food exclusion claimed efficacy in 13 of the 14 studies and was most useful in infants, in patients with elevated immunoglobulin E levels and/or multiple food sensitization and in patients with a diagnosis of food allergy.
Conclusion:  Dietary intervention in the form of an elimination diet is efficacious in children with AEDS when a specific diagnosis of food allergy has been made. Diagnostic evaluation of food allergy should be performed in all children with eczema, particularly in younger children and those with severe forms of the disease.     

Pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is the most common allergic inflammatory skin disease. Interactions of genetic, environmental and immunological factors result in the initiation and progress of AD. Although the clinical picture, characterized by acute flare‐ups of eczematous, pruritic lesions on dry skin at typical predilection such as the flexural folds, is quite homogenous, the trigger factors of the disease are diverse and the pathophysiologic network involved is complex. Therefore, first attempts have been made to classify subtypes of AD based on the most relevant causal factors in the individual patient. To optimize such a stratification of patients, detailed knowledge about cofactors impacting on manifestation of AD as well as impairment of the course of the disease is indispensable. AD shares general features of barrier dysfunction and skin inflammation with other inflammatory diseases of the skin such as psoriasis or allergic contact dermatitis, but a plethora of disease‐specific genetic, immunologic and environmental factors have been identified in AD as well. It is the purpose of this review to illustrate key concepts of the pathogenesis of AD. Important findings of recent years will be summarized and cofactors of the pathogenesis will be controversially discussed. We will summarize knowledge on pathogenic factors on the immunologic level contributing to skin barrier dysfunction in AD and the role of the microbiome as first line of defence. Furthermore, we will elucidate the role of innate lymphoid cells in AD and outline the pattern of T helper cell subtypes present in the skin during different stages of AD.     

Immunopathology of atopic dermatitis

Conclusions In summary, AD is a chronic inflammatory skin disease associated with increased IgE production, eosinophilia, increased mast cell number and increased expression of the CD23 low-affinity IgE receptor on mononuclear cells. The basis of these immunologic defects appear to be the result of increased numbers of IL-4-, IL-5-producing T_h2 cells. This results in an overstimulation of their IL-4-IL-4 receptor pathway that is accompanied by a relative deficiency of IFN- production.The acute manifestations of AD occur as the result of mast cell degranulation that can be triggered by a variety of stimuli including allergens, bacterial toxins or histamine-releasing factors secreted by activated T cells and macrophages. Mast cells release not only histamine which contributes to the acute sensation of pruritus but also cytokines and chemotactic factors which induce leukocyte adhesion molecules and attract inflammatory cells into the local tissue sites [3, 8, 26, 34].The chronic manifestations of AD are probably the result of sustained cellular activation. The cellular infiltrate in the chronic lesion of AD consists primarily of T cells and macrophages [29]. T lymphocytes play two important roles in allergic responses: First, as already discussed they play a critical role in the regulation of IgE responses. Second, there is increasing evidence that they may play an important role in the control of the inflammatory response. This is orchestrated through organization of the cellular composition of the inflammatory cell infiltrate by the release of various cytokines. The release of IL-3, IL-5, and GM-CSF have pronounced effects on the differentiation and activation of eosinophils [52]. IL-3 promotes the growth of mucosal mast cells and stimulates basophil and mast cell histamine release. IL-4 promotes the growth of murine mast cells [18] and induces the expression of CD23 on macrophages [71]. The release of cytokines may, thus, account for the observation of increased mast cell number in chronic eczematoid lesions.Taken together, these observations suggest that the AD skin lesion is characterized by the infiltration of inflammatory cells which differ from those infiltrating into a type IV contact-sensitivity reaction. The sustained immune activation, which results in chronic AD, may be the result of an underlying T cell defect, e.g., decreased IFN- production following the activation of lymphocytes with a variety of stimuli. Treatment of patients withh rIFN- down-regulates the IL-4-IL-4 receptor pathway which is overstimulated in this disease. It is important to note, however, that although many immunopathologic features of AD have recently been elucidated, the fundamental etiology of these abnormalities remains to be unraveled.     

Monitoring of disease activity by measurement of inflammatory markers in atopic dermatitis in childhood

Serum levels of soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule (ELAM-1), and eosinophil cationic protein (ECP) were measured in 20 patients with atopic dermatitis before and after 4 days'treatment with prednisolone p.o. as well as in 16 healthy, nonatopic controls. Before steroid treatment, patients with atopic dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and ECP than healthy controls (P<0.001), whereas ELAM-1 levels were not different between the groups. After 4 days of steroid treatment, clinical improvement was associated with a decrease of sIL-2R (P<0.003), ICAM-1 (P<0.004), and ECP serum levels (P<0.003), but ELAM-1 levels remained unchanged. Both serum ECP and slL-2R levels were significantly correlated with disease severity before as well as after steroid treatment. Changes of sIL-2R concentrations were strongly related to the changes of ECP levels. In addition, changes of serum sIL-2R and ECP levels in percentage were correlated with clinical improvement. These results indicate that the determination of sIL-2R and ECP serum levels may be useful in monitoring disease activity in atopic dermatitis in childhood, especially in treatment trials.