Kristian Thestrup-Pedersen

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

Abstract 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. Key messages This Danish study found that the cumulative incidence of atopic dermatitis at the age of 7 years was 18.7% in 1993 Children born after term had a significantly increased risk of developing atopic dermatitis Children whose birth weight was high for their sex and gestational age also had an increased risk of developing atopic dermatitis These findings suggest that a genetically determined predisposition to developing atopic dermatitis is expressed in utero

Patch test reactivity to nickel alloys

11 widely used nickel alloys were investigated with respect to corrosion stability and reactivity in nickel‐sensitive individuals. Alloys with a nickel release in synthetic sweat exceeding 1 μg/cm2/week gave a strong patch test reaction in nickel‐sensitive persons; those with a release below 0.5 μg/cm2/week showed weak reactivity with one exception. Nickel allergy is a health problem. It may be minimized by using nickel alloys with a corrosion level below 0.5 μg/cm2/week. Action should be taken by dermatologists, industry and authorities to solve this neglected problem.

Long-term, intermittent treatment of chronic hand eczema with mometasone furoate.

Chronic hand eczema can be incapacitating, and there is little knowledge of the efficacy and safety of long‐term treatment with topical corticosteroids. We compared the efficacy and safety of two different schedules for the treatment of chronic hand eczema with a potent topical corticosteroid, mometasone furoate. In a prospective, open, randomized trial, 120 patients with chronic hand eczema were treated daily with mometasone furoate fatty cream until the dermatitis cleared or for a maximum of 9 weeks. Those who cleared were randomized to treatment for up to 36 weeks with mometasone furoate on Sunday, Tuesday and Thursday (group A), mometasone furoate on Saturday and Sunday (group B) or no further corticosteroid treatment (group C). In the event of relapse, patients were permitted daily treatment with mometasone furoate for 3 weeks on two separate occasions. For 50 of 106 randomized patients, daily treatment for 3 weeks controlled their dermatitis; 29 needed 6 weeks and 27 needed 9 weeks of treatment. During the maintenance phase, 29 of 35 (83%) in group A, 25 of 37 (68%) in group B and nine of 34 (26%) in group C had no recurrences (Pu2003=u20030.001, χ2‐test). Side‐effects were minimal. It is concluded that long‐term, intermittent treatment of chronic hand eczema with mometasone furoate fatty cream is effective and safe.

Treatment of lichen planus with acitretin: A double-blind, placebo-controlled study in 65 patients

Sixty-five patients with lichen planus were included in a multicenter trial of acitretin. At the end of an 8-week placebo-controlled, double-blind phase, a significantly higher number of patients treated with 30 mg/day acitretin (64%) showed remission or marked improvement compared with placebo (13%). Furthermore, during the subsequent 8-week open phase, 83% of previously placebo-treated patients responded favorably to acitretin therapy. Typical retinoid adverse reactions were present in all patients on active drug. Laboratory studies did not show any clinically significant changes. This study shows that acitretin is an effective and acceptable therapy for severe cases of lichen planus.

Chemotaxis of human osteoblasts

The in vitro chemotactic response of human osteoblasts was investigated towards the following growth factors: TGF‐β, PDGFs, FGFs and IGFs. Human osteoblasts grown from trabecular bone after enzymatic digestion were studied. TGF‐β stimulated the migration of human osteoblasts in a dose‐dependent manner with a four‐fold increase in migrated cells at 100 pg/ml, which was the optimum concentration. PDGF‐BB also stimulated migration four‐fold in a dose‐dependent manner with a maximum response at 10 ng/ml. PDGF‐AA, IGF‐I and IGF‐II stimulated migration two‐fold at 100 ng/ml. The results show that TGF‐P and PDGF‐BB are important regulators of human osteoblast migration, but other growth factors IGF‐I, IGF‐II and PDGF‐AA may also stimulate osteoblast migration. Our results additionally suggest that TGF‐P and PDGF‐BB may participate in the recruitment of osteoblasts during bone remodeling since both TGF‐P and PDGF‐BB are found in bone matrix and could be released during osteoclastic bone resorption. They furthermore support a possible use of TGF‐P and PDGF‐BB in growth factor‐induced osteogenesis.

Clinical patch test data evaluated by multivariate analysis

The aim of the present study was to evaluate the influence of individual explanatory factors, such is sex, age, atopy, test time and presence of diseased skin, on clinical patch lest results, by application of multivariate statistical analysis. The study population was 2l66 consecutive patients patch tested with the standard series of the International Contact Dermatitis Research Group (ICDRG) by members of the Danish Contact Dermatitis Group (DCDG) over a period of ft months. Fur the 8 test allergens most often found positive (nickel, fragrance‐mix, cobalt, chromate. balsam of Peru, carba‐mix, colophony, and formaldehyde). one or more individual factors were of significance for the risk of being sensitized, except for chromate and formaldehyde it is concluded that patch test results can be compared only after stratification of the material or by multivariate analysis.

Treatment of hyperkeratotic dermatitis of the palms (eczema keratoticum) with oral acitretin. A single-blind placebo-controlled study.

Hyperkeratotic dermatitis of the palms--also called eczema keratoticum--is a chronic, sometimes disabling condition in middle-aged persons. We carried out a single-blind, placebo-controlled study using acitretin in 29 patients. Fourteen patients received active therapy (30mg acitretin daily) and 15 placebo. All had hyperkeratotic changes of the palms with painful fissures and most had involvement of the volar aspects of their fingers. Approximately half of the patients had similar plantar changes. A semi-quantitative score of six parameters was used: hyperkeratosis, fissuring, scaling, itch, redness and vesicle count. After 4 weeks of treatment, a 51% reduction of all symptoms was observed among patients receiving acitretin (p < 0.01) compared with a 9% reduction in the placebo group (p>0.05). No further improvement was seen over another 4 weeks of treatment. There were no changes in blood biochemistry, including serum lipids. No patients discontinued therapy because of side effects. We conclude that 30 mg of acitretin is efficacious and safe to use in patients with hyperkeratotic dermatitis of the palms.

Expression of CCR2 on monocytes and macrophages in chronically inflamed skin in atopic dermatitis and psoriasis

Monocytes form a significant component of the inflammatory reaction taking place in the skin of atopic dermatitis and psoriasis. Chemokines are pivotal in mediating the attraction of leucocytes to sites of inflammation. The CC-chemokine, monocyte chemotactic protein 1 (MCP-1/CCL2), is expressed by keratinocytes in both atopic dermatitis and psoriasis. MCP-1 binds to the chemokine receptor CCR2 which is known to be expressed on monocytes and macrophages. We examined the expression of CCR2 on peripheral blood monocytes from patients with psoriasis (n=8) and atopic dermatitis (n=7) and found it to be expressed on approximately 90% of the cells, whereas monocytes from healthy donors had a significantly lower CCR2 expression (p<0.05). Skin biopsies from patients suffering from atopic dermatitis and psoriasis revealed that CCR2-positive cells expressed CD163, a marker for monocytes/macrophages. However, not all CD163-positive cells expressed CCR2, which could be interpreted as a mechanism for retaining the macrophages in the skin. Furthermore, we found that keratinocytes are able to express MCP-1, when stimulated with tumour necrosis factor-alpha and/or interferon-gamma in a dose-dependent manner. Thus MCP-1 and CCR2 interaction is likely of importance for the monocyte/macrophage trafficking of inflammatory skin disorders.

1,25(OH)2-D3 is a potent regulator of interleukin-1 induced interleukin-8 expression and production.

Interleukin 8 (IL-8) is a potent leukocyte chemotactic and activating cytokine produced by keratinocytes, fibroblasts, peripheral blood monocytes (PBMC) and endothelial cells. IL-8 is believed to play an important role in the development of inflammation and is thus an obvious target for therapeutical modulation. We studied the possible effect of an endogenous immune modulator 1,25(OH)2-cholecalciferol (1,25(OH)2-D3) on the IL-1-induced IL-8-production by several types of cells. 1,25(OH)2-D3 inhibited the IL-1-alpha induced IL-8 production and mRNA expression in keratinocytes, fibroblasts and PBMC, but not in endothelial cells. Optimal vitamin concentrations varied between 10(-10) and 10(-11) M. These results suggest a potential role of this hormone in the regulation of chemotactic cytokine production.

EPSTEIN-BARR-VIRUS-INDUCED LYMPHOPROLIFERATIVE DISORDER CONVERTING TO FATAL BURKITT-LIKE LYMPHOMA IN A BOY WITH INTERFERON- INDUCIBLE CHROMOSOMAL DEFECT

A 6-year-old boy presenting with swelling of cervical and axillary lymph-nodes was diagnosed as having an Epstein-Barr virus infection because of EBV-nuclear-antigen-positive B-lymphocytes in blood and lymph nodes and high antibody titres to EBV antigens. The natural killer activity of blood-lymphocytes was low, and so was the percentage of T-lymphocytes with Fc receptors for IgG (T-gamma cells). Chromosomal studies revealed a defect in the long arms of one of the chromosomes in pair no. 16 (16q22). The defect only appeared after addition of interferon to the lymphocyte cultures and preferentially in T-gamma lymphocytes. The disease progressed despite attempts to restore the patients immune reactivity by interferon, transfer factor, and blood transfusions. Necropsy showed that the severe hyperplasia of lymph nodes found during life had become a Burkitt-like lymphoma. The possible connection between an interferon-induced chromosomal defect (break at 16q22) and reduced level of natural killer activity, reduced T-gamma lymphocytes, and proliferation of EBV-positive B-lymphocytes is discussed.