Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients.

Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin with active eczema in 8 adults with AD and from clinically normal skin from 4 of the patients. Five persons without allergy or skin disease served as controls. The mean number of lymphocytes in 4-mm skin biopsies was 469,000 and 124,000 in active eczema and in clinically normal skin, respectively. Compared with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically moderate AD has a considerable number of lymphocytes in the skin.

Purified Der p1 and p2 patch tests in patients with atopic dermatitis: evidence for both allergenicity and proteolytic irritancy.

Atopic dermatitis has many similarities with allergic contact dermatitis. Previous studies have revealed delayed-type allergic reactions indicating specific cell-mediated immune reactions in subgroups of patients. It has recently been recognized that purified house dust mite major allergens, Der p1 and Der p2 from Dermatophagoides pteronyssinus, exhibit a proteolytic enzyme activity similar to papain and maybe serine proteases (e.g. trypsin), respectively. This opens the possibility that house dust mites apart from an allergic epitope could elicit irritant reactions in atopic skin. We examined cutaneous reactivity to the purified proteins of house dust mite antigens, Der p1 and Der p2, in 36 consecutive patients with atopic dermatitis. We also patch-tested with trypsin and papain, in order to see if these proteolytic enzymes could induce irritant reactions. Twelve patients had type 1 allergy to Der p1 and two of these had type IV reactivity to D. pteronyssinus extract. Positive reactions were observed in another four patients, but they had also irritant reactions to papain and trypsin, indicating that the enzymatic activity may have elicited the reactions. The cutaneous reactivity was not linked to total serum IgE, but the patients with specific allergic patch tests had type I reactions to D. pteronyssinus extract. Our observations indicate that allergic patch tests towards Der p1 and p2 are rare and that irritant reactions from D. pteronyssinus proteolytic activity may be a more common phenomenon when patch-testing atopic dermatitis patients with house dust mite antigen extract.

Atopic dermatitis and birth factors: historical follow up by record linkage.

OBJECTIVE: To study if factors at birth are associated with later development of atopic dermatitis. DESIGN: Historical follow up by record linkage from Danish medical birth register. Children were followed up for 5.5 to 8.5 years. Second historical follow up study comprising questionnaire to mothers of singleborn children 6.5 to 9.5 years after birth. SETTING: Private dermatology clinics and dermatology and paediatric departments in the municipality of Aarhus, Denmark. SUBJECTS: 7862 singletons born in hospital between 1 January 1984 and 31 December 1986 to mothers living in the municipality of Aarhus. Questionnaires sent to 985 mothers. MAIN OUTCOME MEASURES: Gestational age, birth weight, parity, and age of mother at the time of birth. Atopy in children diagnosed by specialists in dermatology and physicians. Family size; diagnosis of atopic dermatitis, allergic rhinitis, and asthma; family predisposition; and mothers' smoking habits during pregnancy determined from questionnaires. RESULTS: Of 7862 children, 403 were diagnosed as having atopic dermatitis by a specialist; the cumulative incidence at age 7 was 5.6%. High gestational age and low parity were associated with an increased risk of atopic dermatitis. Among 985 children atopic dermatitis had been diagnosed by any physician in 184; the cumulative incidence at age 7 was 18.7%. High birth weight, high gestational age, and family history of atopy were associated with increased risk of atopic dermatitis. CONCLUSION: In both studies the incidence of atopic dermatitis was associated with high gestational age and in one with high birth weight also. The causes for these associations are at present unknown but may indicate that even during gestation factors associated with atopic dermatitis influence maturation.

Atopic dermatitis may be a genetically determined dysmaturation of ectodermal tissue, resulting in disturbed T-lymphocyte maturation. A hypothesis.

Although atopic dermatitis is a skin disorder, it includes immune deviations such as T-cell accumulation and activation in the skin, resulting in chronic, relapsing eczema. The T-lymphocyte activation in the skin is not accompanied by specific allergies in up to two thirds of the patients. It has been shown that T-cell lines and clones can be established from skin biopsies of patients with atopic dermatitis showing cytokine-dependent, but antigen-independent, continuous growth in vitro. This indicates the existence of skin-homing T-lymphocytes with growth requirements different from those of mature T-lymphocytes in the blood. We suggest that atopic dermatitis is a genetically determined change of ectodermal tissue. The thymic epithelium is derived from the ectoderm, and because of that we hypothesize that the maturation of the T-cell immune system of persons who develop atopic dermatitis is disturbed due to a faulty selection of T-lymphocytes in the thymus. "Dys"-matured T-cells leave the thymus as a consequence of faulty selection and continue their growth in the skin. The cells are eventually eradicated by the immune surveillance conducted by the normal part of the patients' immune system and as a consequence of diminished output of faulty selected T-lymphocytes during maturation. Because of the increased proliferation capacity of the aberrant T-cells, a cytokine imbalance occurs and in some patients this leads to the development of type I allergies due to a skewing of the humoral immune system towards IgE production.

Atopic dermatitis may be linked to whether a child is first- or second-born and/or the age of the mother.

Five hundred and thirty families with at least 1 child who had been referred to a dermatologist with atopic dermatitis were interviewed in an effort to determine whether factors such as the age of the mother when a child is born and/or birth rank can contribute to the development of atopic dermatitis. The families interviewed had a total of 1,084 children, or an average of 2 children per family. Sixty per cent of the children with atopic dermatitis were under 5 years of age. Ninety-one per cent of them had developed the disease before the age of 3; those most severely affected had developed the disease during the first year of life. In families with 2 children, but only 1 child with atopic dermatitis, the odds ratio for the second child to develop atopic dermatitis was 1.379 (0.025 < p < 0.05). The average maternal age was 24.8 to 25.2 years when giving birth to the first child and 28 years when giving birth to the second child, irrespective of the status of the child. Thus, atopic dermatitis can be related to birth rank or to the age of the mother.

Treatment of chronic idiopathic urticaria with topical steroids. An open trial.

Twenty-three patients with chronic idiopathic urticaria and 3 patients with urticaria pigmentosa received a 2-week treatment with daily application of potent topical steroid using plastic occlusion. Seventy per cent of the chronic urticaria patients had a statistically significant, immediate response, which, however, did not last until the final evaluation after 1.5 years. Relapse occurred after on average 3 weeks, but 39% reported less severity. The 3 patients with urticaria pigmentosa remained free from attacks for 6 to 9 months, after which they gradually relapsed. Two women were diagnosed during the follow-up period to have a carcinoma of the breast, and one patient developed systemic lupus erythematosus.