Agreement between different criteria for diagnosing AE was acceptable, but the mild cases constituted a diagnostic problem, although they were in the minority. Repeated examinations gave better agreement between diagnostic criteria than just one examination. Atopic heredity was less predictive for AE than sensitization to common food and inhalant allergens in early childhood.
Longitudinal studies in infant populations using validated diagnostic criteria of atopic dermatitis and sensitization are rarely reported, and disease definitions, testing procedures, age of study population and evaluation of objective markers vary between countries and studies. The objectives of this prospective birth cohort study were to investigate: (i) the prevalence, the cumulative incidence and the pattern of transient and persistent sensitization to common food- and aeroallergens in unselected infants, (ii) the association between sensitization and the development of atopic dermatitis (AD) and (iii) the association between selected perinatal risk factors with respect to AD and post-natal sensitization. During a one-year period a cohort of 562 unselected newborns was established and followed up at the age of 3, 6, 9, 12 and 18 months of age. At all time points infants were examined clinically and by histamine release (HR), total- and specific immunoglobulin E (IgE) and skin prick test (SPT). Sensitization ever to > or =1 allergen at 18 months of age was 59%, 50% and 6% using HR, IgE and SPT, respectively. A transient sensitization to > or =1 allergen was found in 47%, 42% and 4% and a persistent sensitization in 17%, 10% and 3%, respectively. Sensitization to environmental allergens was frequently observed in infancy when testing with HR and IgE. Results of SPT gave much lower frequencies. Reactivity to foods was more frequent than to aeroallergens. The dominant pattern was low-level transient sensitization. This is important to know when sensitization tests are used in the course of examination of infants with eczematous skin diseases. Specific definitions of sensitization like persistent reactivity, high-level sensitization and poly sensitization were clearly associated with AD. A maternal history of AD was a valuable tool in predicting AD in early infancy; a similar finding was less obvious with regard to post-natal sensitization. Cord-specific IgE and cord-HR positive reactivity did not prove better tools than cord-total IgE in predicting AD within the first 18 living months.
The pattern of patch test reactivity to nickel sulfate and fragrance mix was studied with respect to patch test performance, reproducibility and clinical relevance in a population of unselected infants followed prospectively from birth to 18 months of age. TRUE Testtrade mark patches with nickel sulfate in 3 concentrations, 200, 66 and 22 microg/cm(2), and fragrance mix 430 microg/cm(2) were used. A likely case of nickel sensitivity was defined as a reproducible positive reaction with at least homogeneous erythema and palpable infiltration occurring at least 2x and present at both the 12 and 18 months follow-up. 543 infants (268 girls and 275 boys) were tested at least 1x, 304 were tested at both 12 and 18 months. The prevalence of a reproducible positive reaction to nickel was 8.6% (20 girls and 6 boys). A transient positive reaction was observed in 111 children. Clinical relevance of nickel sensitivity was found in only 1 child. No reproducible positive reaction to fragrance mix was found. The high proportion of transient patch test reactivity to nickel sulfate 200 microg/cm(2) indicates that this standard concentration used for adults cannot be applied to infants. The interpretation of a single positive nickel patch test in infants must be assessed with caution and it is probably of non-specific or irritant nature.
Psoriasis is characterized by hyperproliferation and impared differentiation of epidermal keratinocytes (KCs). Psoriasis can be treated with derivatives of retinoic acid (RA) and vitamin D3. Analogues of vitamin D3 are able to inhibit proliferation and stimulate differentiation of KCs. In contrast, RA inhibits terminal differentiation of KCs. Interactions are known to occur between RA and vitamin D3 signalling pathways. The purpose of the present study was to determine the effect of all-trans RA on the binding of 1,25-dihydroxy-vitamin D3 (1,25 (OH)2D3) to the vitamin D3 receptor (VDR) of cultured human KCs. Cultured KCs from normal adults were incubated with or without RA (10-9-10-7M) for 4-24 h. Cells were then harvested, homogenized and ultrasonicated. The extracted protein was incubated with 3H-1,25 (OH)2D3 (0.015-1.0 nM) with or without 250-fold excess nonradioactive 1,25 (OH)2D3 for 24 h and specific binding was determined by use of the dextran coated charcoal binding assay. Western blot analysis utilizing the monoclonal antibody 9A7 gamma to VDR was performed on protein extracted from the KCs. The bands resulting from Western blot analysis were visualized by enhanced chemiluminescence. From Scatchard analysis it was found that KCs bind 1,25 (OH)2D3 with high affinity (Kd = 0.175 nM). This binding was dose and time dependently inhibited by RA (60% inhibition at 10-7 M after 24 h of incubation). By Western blot analysis, RA had no effect on the amount of protein extracted from KCs at any of the RA concentrations tested. In conclusion, these results show that binding of vitamin D3 to its receptor of human KCs can be inhibited markedly by RA without effecting the amount of protein. These results are in contrast to results with other cell types in which RA upregulates binding of 1,25 (OH)2D3 to the VDR. Because interaction between retinoids and vitamin D3 may occur at different levels during signal transduction, it is not possible to predict from our results whether RA will inhibit the effects of vitamin D3 in vivo.
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