Quantitative analysis of tryptase- and chymase-containing mast cells in atopic dermatitis and nummular eczema

The distribution of mast cells (MCs) containing tryptase (T) and chymase (C) was studied in the non-lesional and lesional skin of 26 patients with atopic dertnatitis (AD) and 23 patients with non-atopic nummular eczema (NE). and in the skin of eight healthy controls. T and C activities were demonstrated enzymehistochemically using 2-Gly-Pro-Arg-MNA and Suc-Val-Pro-Phe-MNA as substrates, respectively. The T- and C-containing MCs were counted separately in the epidermis, in contact with the basement membrane. In the papillary dermis and in different dermal levels (0·2 mm each). Also, the C protein was determined immunohistochemically. T-positive MCs were similarly distributed in non-lesional and lesional skin of both AD and NE. The MC number was relatively high in the upper dermis (papillary dermis and levels I and I!) of non-lesional and lesional skin of AD. In the upper dermis of non-lesional AD and NE skin and in normal skin, about 50% of T-positive MCs displayed C activity, whereas the percentage in lesional AD and NE skin was only about 30%. hi this respect, the non-lesional and lesional samples differed significantly froLu each other in both dennatoses (in AD p = 0%005, in NEP = 0·002. Students' t-test). In all samples the MC number decreased in the deeper dermal levels, although numerous T-containing MCs were still counted in the deeper dermis (dermal levels IV-VII) of lesional AD and NE skiti. differing significantly from the MC number in normal skin (In ADp = 0·005. in NE p=0·041). In the deeper dermis. the percentage of MCs containing active C was about 70% in non-lesional and lesional AD and NE. and about 90% in normal healthy skin. However, in the upper dermis of non-lesional and lesional skin of both AD and NE. about H()% of all MCs contained the C protein, which differed significantly from the value of 100% in normal skin (p<0·5). In conclusion, the increased number of T-positive MCs in the upper dermis of non-lesional and lesional AD contributes to promoting inflammation. C apparently loses its activity in the upper dermis of lesional AD and especially in NE. Thus. Ihe enzyme partially lacks its capability to suppress inflammation, such as degradation of neuropeptides and proteins. The dysregulation of these proteinases exists already in non-lesional skin of AD and NE.     

Effectiveness of dupilumab for the treatment of nummular eczema phenotype of atopic dermatitis in adults

Nummular eczema (NE) is currently considered as one of the clinical phenotypes of atopic dermatitis (AD) of the adult. In this multicentre study, 30 adult patients (age ≥ 18 years) affected with nummular‐like AD were treated with dupilumab, a monoclonal antibody against the receptor for interleukin(IL)‐4 and IL‐13. The evaluation of the results after 16 weeks of treatment showed a significant improvement of the disease, as demonstrated by reduction in Eczema Area Severity Score (EASI), visual analogue score (VAS) of pruritus, and Dermatology Life Quality Index (DLQI) scores. Conjunctivitis in one patient was the only side effect. In conclusion, dupilumab seems to be an effective and safe treatment in NE phenotype of AD of the adult.     

肥大细胞在特应性皮炎发病中的研究进展

特应性皮炎是一种与遗传过敏素质有关的慢性、复发性、瘙痒性、炎症性皮肤疾病，其病因复杂，发病机制尚未明确。近年来，随着对特应性皮炎直接相关的效应细胞及效应分子，特别是肥大细胞及其表达的细胞因子的深入研究，逐步明确肥大细胞在特应性皮炎炎症过程中迁移、聚集、局部数量增多的机制，以及肥大细胞与嗜酸粒细胞、T细胞之间相互作用的关系。其结果将有助于进一步理解特应性皮炎皮肤炎症的细胞基础，并可能为临床治疗提供新的靶点。     

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis. Received: 17 April 1996     

Skin reactivity to neuropeptides in atopic dermatitis

Adults with atopic dermatitis (AD), with respiratory atopy only and healthy non-atopic controls were given intradermal injections of substance P (SP), neurokinin A (NKA), neurotensin (NT), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and histamine into the normal-appearing skin on the back. The weal and flare responses were evaluated after 3, 5 and 15 min and the areas calculated using an automatic image analyser. With the three different concentrations used (1, 3 and 30 pmols) a statistically significant (P less than 0.05) reduction in both the weal and flare response to SP, NKA, NT and histamine and a reduced flare to CGRP was observed only in AD patients. Among those with AD there was no uniformity of response to the individual neuropeptide and in general the more severely affected showed a lower reactivity. Dose-response relationships were evaluated for SP and NT (10-320 pmols) in AD and healthy controls. In AD dose-response curves and time-course relationships were similar to controls, but at significantly reduced levels. The itch response to the neuropeptides and histamine was not different in atopics and controls. We suggest that this hyporesponsiveness in AD is the result of natural tachyphylaxis of the target structures (mast cells and blood vessels) and possibly due to a higher availability of neuropeptides in the skin or to a primary abnormal sensitivity of the blood vessels and mast cells to these peptides.     

Mast cells and IgE in intestinal mucosa in adult atopic dermatitis patients

Duodenal biopsies from 29 adult atopic dermatitis (AD) patients with multiple positive skin prick test reactions were examined and the results compared with biopsies from 13 non-atopic controls. The duodenal mucosa showed mild inflammatory changes in six out of the 29 patients, but was normal in all the controls. Numerous anti-IgE positive cells, increasing with the severity of AD, were found in the duodenal mucosa in 25 of the 29 AD patients compared with few sporadic positive cells seen in only two out of 13 controls (P less than 0.001). The total serum IgE level showed a significant positive correlation with the number of anti-IgE stained cells in the mucosa (P less than 0.05). No significant differences were found in the total number of toluidine blue stained cells or cells immunoreactive for histamine between patients and controls. However, AD patients who had high numbers of anti-IgE positive cells often had decreased numbers of histamine immunoreactive cells in the mucosa suggesting mast cell degranulation. These findings provide further evidence that also in adult AD patients the gastrointestinal tract may serve as a portal of entry for allergens which may lead to exacerbation of AD.     

Mast cells are one major source of interleukin-4 in atopic dermatitis

Several reports have shown the presence of T-helper lymphocytes with Th2 characteristics in the skin lesions of atopic dermatitis (AD). However. Th2 cells themselves require an exogenous pulse of IL-4 to initiate their differentiation and synthesis of IL-4. As mast cells have recently been shown to contain IL-4, this finding prompted us to investigate IL-4 in mast cells of AD lesions, to determine if they might provide the IL-4 pulse needed by the Th2 cells. In this study, we measured IL-4 immunoreactivity in mast cells of non-lesional and lesional skin sections from 20 patients with AD. Ten patients with nummular eczema (NE) without any atopic features or background, and five healthy subjects, served as the control groups. Mast cells were first identified using an enzyme-histochemical staining method for tryptase. Subsequently, the sections were photographed, the tryptase stain was removed, and IL-4 was demonstrated with a polyclonal antibody. The sections were photographed again, and the percentage of IL-4-positive mast cells was calculated. The percentage of mast cells exhibiting IL-4 immunoreactivity in the upper dermis in lesional vs, non-lesional skin was 66±18% vs. 37±18% in AD (P<0.0001, paired t-test), but only 46±19% vs. 31±22% in NE. In the skin of healthy controls, only 23±25% of the mast cells were positive for IL-4. In addition, a significant difference was found between lesional skin of AD vs. NE patients (P<0.008, unpaired t-test). Moreover, the staining intensity of IL-4 in mast cells was clearly increased in the lesional compared with the non-lesional AD skin. Mast cells appeared to be the main cell type containing IL-4 in 40% of the lesional AD skin specimens, whereas in the remaining 60% prominent IL-4-positive mononuclear cell infiltrates were also present. In the non-lesional skin, mast cells appeared to be the main cell type containing IL-4 in all specimens. These results indicate that mast cells are one major source of IL-4 in lesional and non-lesional AD skin, and they could contribute significantly to the development of AD.     

Effectiveness of dupilumab in pediatric patients with a nummular phenotype of atopic dermatitis

The nummular phenotype of atopic dermatitis is clinically characterized by pruritic, coin-shaped plaques that are frequently recalcitrant to treatment. In this study, a retrospective chart review was conducted to evaluate the effectiveness and safety of dupilumab in children with nummular lesions of dermatitis. Twelve out of 14 patients demonstrated significant clinical improvement at a median time of 2.5 months (interquartile range, 1–4) after dupilumab initiation. A single case of paradoxical psoriasiform eruption was the only side effect reported in our cohort.     

The role of selected neuropeptides in pathogenesis of atopic dermatitis

Background Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. Objective The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Material and methods Forty‐nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Results Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation.     

Immunoglobulin- and complement-bearing lymphocytes in allergic contact dermatitis and atopic dermatitis (eczema)

The distribution pattern of immunoglobulin- or complement-bearing lymphocytes in healthy controls and in patients with contact dermatitis and with atopic dermatitis has been investigated. A significant predominance of IgD- and C₃-bearing lymphocytes was found in ten patients with contact dermatitis. In atopic dermatitis patients the number of IgE- and to a lesser extent of C₃-bearing lymphocytes was increased. The results indicate induction of stimulation of two distinct classes of immuno-logically competent lymphoid cell lines, one in contact and the other in atopic dermatitis. The increased number of B-cells in dermatitis indicates a decreased T-cell population and suggests a deficiency or disturbance of the recirculation of this population.     

Prevalence of atopic eczema in the community: the Lothian atopic dermatitis study

Summary An epidemiological study of atopic eczema (AE), based on a semirural community in Scotland, using sound diagnostic criteria, has yielded prevalence data for all age groups including infants and adults. The overall 1-year period prevalence, age-standardized to the Scottish population, was 2.3%. The 1-year period prevalence was highest in the under 2s(9.8%), and showed a continuous reduction with increasing age. Over the age of 40, AE was found to be relatively rare, with a 1-year period prevalence of 0.2%. Adults over 16 years made up 38% of all patients with AE.