Hidetoshi Kawahara

Hypoproteinemia in severe childhood atopic dermatitis: A serious complication

As a complication of atopic dermatitis (AD), the incidence of hypoproteinemia is increasing among infants with severe AD in Japan. It can be a life‐threatening condition owing to hypovolemic shock as a result of hypoproteinemia and vascular infarction as a result of thrombocythemia. However, the pathophysiology of this condition remains unclear. The objectives of the present study were two‐fold. The first objective was to determine the main route of protein loss, i.e. through the damaged skin or the gastrointestinal tract, or as a result of insufficient food intake. The second objective was to identify whether allergy or infection was the cause of severe skin inflammation. Fifteen patients with AD were enrolled who had serum protein levels of 3.2–5.8 g/dl. Specific immunoglobulin E (IgE) and skin test to allergens, stool eosinophils, α1‐antitrypsin clearance, skin Staphylococcus aureus colonization and superantigens (SAgs) produced by the organism, serum SAg‐specific IgE antibodies, serum interleukin (IL)‐5, IL‐6, IL‐12, and interferon‐γ (IFN‐γ) were evaluated. Prominent serous skin discharge was seen in all of the patients and was found to have almost the same protein concentration as serum. Marked thrombocytosis, with a maximum of 1,060 × 103/ml, was seen. Skin culture revealed S. aureus colonization in all patients. SAg‐producing S. aureus were found in 84.6% of the patients. The concentration of serum IL‐5 was significantly increased and correlated well with the blood eosinophil count. Hence, the main route of protein loss was believed to be through damaged skin. The cause of severe inflammation was thought to be a combination of allergic inflammation and skin colonization by SAg‐producing S. aureus. Serum cytokines showed a T helper 2 (Th2) T‐cell‐mediated pattern. To prevent hypovolemic shock, vascular occlusion, and growth retardation, it is of vital importance to diagnose hypoproteinemia at an early stage and start appropriate therapy.

Impaired Interferon-γ Production in a Subset Population of Severe Atopic Dermatitis

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic chronic eczema. The immunopathogenesis of this condition is still not well understood. We assessed the transcription and production of IFN-γ, the Th1 cytokine, and the Th2 cytokine IL-5 in peripheral blood mononuclear cells (PBMCs) from patients with severe AD. Methods: The subjects included 17 severe (serum IgE: 5,000–92,000 U/ml, median: 20,000 U/ml), 4 mild AD (IgE: 2–520 U/ml) and 8 nonatopic controls (IgE: <100 U/ml). The severe AD patients were classified into two groups according to the response to standard treatment with topical glucocorticoids. Individuals were classified as poorly responsive (AD-P) if the clinical score decreased less than one third after 2 weeks of hospital treatment and as responsive (AD-R) if the score decreased more than one third. PBMCs isolated from the subjects were stimulated with PHA and PMA. Results: The expression of IFN-γ in PBMCs in the AD-P group was much lower than that observed in the other groups at both mRNA and protein levels. There were no significant differences in the levels of IL-5 both in mRNA and protein levels between the groups. There were no significant differences in STAT4 DNA-binding activity following PHA/IL-2/IL-12 stimulation between AD-P and controls. Conclusions: These results suggest that the decreased INF-γ production may account for the abnormal immunopathogenesis of severe, intractable AD.

Human mast cell progenitors in peripheral blood from atopic subjects with high IgE levels.

Background It remains unclear whether the number of circulating mast cell progenitors is increased in patients with atopic diseases. Distinct genotypes are reported to affect mast cell/basophil activation.

Continuous Isoproterenol Inhalation Therapy in Children with Severe Asthmatic Attack

We studied the 1-type isoproterenol inhalation therapy for patients with severe asthmatic attacks who were admitted at the Department of Allergy of National Childrens Hospital from 1981 to 1991. One hour after l-type isoproterenol inhalation therapy, statistically significant effects were noted with regard to the asthmatic status. Moreover, no side effect was found amoung the subjects. From these data, 1-type isoproterenol inhalation therapy is thought to be effective for severe asthmatic attacks.

Analysis of Gene Expressions of T Cells from Children with Acute Exacerbations of Asthma

Background: Little is known about airway inflammation in childhood asthma. The aims of this study were to analyze the expression of a wide range of mediators of airway inflammation in childhood asthma. Methods: Eight asthmatic children with acute exacerbations were recruited for the study. Peripheral blood was drawn from the patients at the time of exacerbation and after improvement. Total RNA was extracted from the isolated T lymphocytes. The differential display (DD) RT-PCR method was used to detect expressed genes, and the quantification of candidate gene expression was performed using real-time quantitative RT-PCR. Results: The only gene for which significant expression differences were detected in both DD analysis and quantitative RT-PCR was lipocortin II (annexin II) (exacerbation > remission, p < 0.05). In quantitative RT-PCR of interleukin-4 (IL-4), IL-5, interferon-γ, IL-12 receptor-β and integrin α6, a significant difference was found only in the expression of IL-4 mRNA (exacerbation > remission, p < 0.05). The IL-4 plasma concentration tended to be higher in exacerbation than in remission. Conclusions: Our findings suggest activation of T cells and IL-4 production may be involved not only in the basic pathogenesis of childhood asthma but also in its acute exacerbation, and that lipocortin II may be a marker or contribute to asthma exacerbation.

Hypoalbuminemia, oliguria and peripheral cyanosis in an infant with severe atopic dermatitis

A six‐month old male infant with severe atopic dermatitis was admitted with hypoalbuminemia, oliguria and cyanosis of the extremitie. s. There was marked edema and generalized eczema with foul, yellowish exudates. The patients major clinical manifestations were attributed to the loss of albumin through the skin. Although atopic dermatitis is a common disease in children, here we want to show that systemic disturbances may arise from such condition, describe the total care given the patient, and emphasize the wholistic approach in managing cases of severe atopic dermatitis, intensive treatment was instituted and the patient was discharged after three weeks and remained in a stable condition.

Rupert Timpl – A Personal Account

Accessible online at: www.karger.com/iaa The message of Rupert Timpl’s (fig. 1) untimely and unexpected death on October 20, 2003, struck me completely unprepared during a hiking tour through the Dolomites in Northern Italy, just across the Austrian border, a few miles from my hometown Innsbruck in Tyrol, Austria. It was brought to me by one of my students who hiked with our group and who had just spent a few days in Martinsried at the Max-Planck Institute for Biochemistry (MPI) near Munich, Germany, where Rupert has worked for nearly three decades – the last years as Head of the Department of Connective Tissue Research and as Acting Director of the whole MPI before his retirement in 2000. During that beautiful clear October day in the Dolomites (fig. 2) with several hours of walking time before me, the sudden confrontation with the fact that I would not see Rupert again, afforded the opportunity to immediately and intensively reflect on the role that he played both in my professional as well as in my private life. It first came to my mind that of all the associates of Rupert my own connection was the longest lasting, since it already started in 1965 when we first met in a small laboratory of a peripheral hospital, the Hanuschkrankenhaus, in Vienna. At that time, I was on my first postdoctoral position at the Institute for General and Experimental Pathology, University of Vienna, Medical School, where one of our associate professors, Carl Steffen, had a joint appointment as the head of the Central Diagnostic Laboratory of that hospital. There, Steffen had started a group of connective tissue immunologists, led by the young eager beaver Rupert, at that time still a graduate student who already had an impressive list of highly cited publications and – typically for him – also supervised three postdocs, Fig. 1. Dr. Rupert Timpl, Max-Planck-Institut für Biochemie, Martinsried.

To read food material labeling, it is important to understand cross-reactivity of IgE antibody

Abstract Rationale Food material labeling rule was effective April 2002 in Japan. Twenty-four food materials must be labeled on package. Twenty-four food materials are following; hen egg, milk, wheat, buckwheat, peanut, bearded clam, calamari, salmon roe, shrimp, orange, crab, kiwifruit, beef, walnut, salmon, mackerel, soybean, chicken, pork, matsutake mushroom, peach, yam, apple, gelatin. However most of foods cross-react with much food with same protein sequence. We should recognize cross-reactivity among food materials. Methods 80 children with any food allergy to food mentioned above were enrolled. IgE cross-reactivity was measured by inhibition ELISA and inhibition immunoblotting methods among (a) hen egg and salmon roe, (b) salmon roe, herring roe and Pollack roe, (c) salmon and salmon roe, (d) yam, Irish potato and sweet potato, (e) peanut, almond and cashew nut. Results There is no cross-reactivity of specific IgE among hen egg and salmon roe. Cross-reactivity among fish roes, potatoes, nuts was observed. Conclusions Because cross-reactivity is present among much food, it is necessary to well understand the thing when we watches food labeling.