Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na–K-acetate (300–600 mOsm/kg H₂O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represesented 3 very distinct populations with respect to total plasma IgE content, medians were <0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml, respectively. Increasing osmolarity to 500 mOsm/kg H₂O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H₂O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsM/kg H₂O. Responses were highly correlated to results at 300 mOsm/kg H₂O. The use of 600 mOsm/kg H₂O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by incrased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays use in allergy diagnosis.     

Treatment principles of atopic dermatitis

Atopic dermatitis (AD) is today the most common, chronic inflammatory skin disease among children in developed countries. Its cumulative prevalence varies from 20% in northern Europe and the USA to approximately 5% in Mediterranean countries. As a chronic disease it puts a special demand on treatment. There is no curative therapy, but competent guidance on treatment principles can control the disease in most, if not all children. This article summarizes the evidence-based knowledge that relates to the treatment of atopic eczema. It also gives advice and opinions on prophylactic measures as these are the focus of interest from most parents. LEARNING OBJECTIVE: This article should enable you to give advice and guidance to parents of children with AD, including what is necessary for diagnosis, what is of value and importance considering allergies and allergological investigations, allergen exposure, prophylactic measures, diets and indoor environment. Finally, you should be able to explain the diversity of treatment principles for parents.     

The red man syndrome: Exfoliative dermatitis of unknown etiology: A description and follow-up of 38 patients

Thirty-eight patients with erythroderma of unknown etiology were diagnosed over a 15-year period, and represented 19% of all patients admitted to our department for erythroderma. The male:female ratio was 6.6:1, and the median disease duration was 2 years (range 1 to 23 years). Keratoderma of palms and/or soles was seen in 79%. Laboratory findings were normal, except for an increased IgE level in 69% of the patients studied. Lymph node histology showed dermatopathic lymphadenopathy. Bone marrow investigation results were normal in 48%, or showed eosinophilia (32%) or hyperplasia (20%). Initial skin biopsies showed nonspecific histology in most patients, but later biopsies revealed pleomorphic infiltration. During the observation period four patients progressed to mycosis fungoides and another nine patients were suspected of having mycosis. None developed Sézary's syndrome. Only one third of the patients went into complete remission; half of them died during the observation period. Patients with erythroderma of unknown etiology are predominantly men and seem to belong to a certain subgroup--herein called the red man syndrome.     

Subpopulations of T lymphocytes and non-specific suppressor cell activity in patients with atopic dermatitis.

Thirty-five adult persons with moderate to severe atopic dermatitis and increased levels of IgE in serum were studied for the presence of Fc-IgG (T gamma) and Fc-IgM (T mu) receptor-carrying T lymphocytes in peripheral blood. When T lymphocytes from the patient were kept in vitro cultures a reduced expansion of the Fc-IgG receptors was found after 24 hr of incubation, but not after 48 hr of incubation. No difference was observed concerning Fc-IgM-carrying T lymphocytes. In 19 patients we studied Con A-induced suppressor activity of blood lymphocytes using autologous PHA-stimulated lymphocytes as target cells. Following stimulation with Con A, 1 microgram/ml, for 2 and 4 days, lymphocytes from atopic patients had a reduced non-specific suppressor activity in vitro. If however, the concentration of Con A was increased to 10 microgram/ml, then lymphocytes from atopic patients exhibited a normal suppressor activity.     

Atopic dermatitis is increased following vaccination for measles, mumps and rubella or measles infection

The prevalence of atopic dermatitis increased markedly in the period 1960s to the 1990s. Earlier findings indicate that infections acquired in early life enhance or suppress the expression of atopic disease as a result of a change in immune reactivity. Our objectives were to examine the association between measles, mumps and rubella vaccination, measles infection and the risk of atopic dermatitis. A random sample of 9,744 children were followed up from birth to 3-15 years. Their parents responded to a questionnaire including highly structured questions on atopic dermatitis, measles, mumps and rubella vaccination and measles infection. Information on parental educational level was obtained from Statistics Denmark. The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella vaccinated children versus children not subjected to measles, mumps and rubella vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence ratio for measles-infected children was similar. The incidence of atopic dermatitis increased after measles, mumps and rubella vaccination and measles infection, which is surprising in view of the hygiene hypothesis. We suggest further study of the possible short-term and long-term effects of virus and bacteria on the immune responses and expression of atopic disease.     

Lymphocyte transformation test with liver-specific protein and phytohaemagglutinin in patients with liver disease.

(1) A new antibody has been found by immunofluorescence which reacts with cardiac conducting tissue using ox heart false tendons. It was detected in eight out of ninety-three cases of idiopathic heart block (8-6%), in one out of twenty-two cases of secondary heart block (4-5%) and in seven of 165 normal controls (4.2%), in titres varying from 1:10 to 1:40. Previous authors had indicated that this tissue might contain unique antigens. (2) Sera reacting with type I fibres in skeletal muscle (red zebra) were found to be of two varieties, one of which stained conducting fibres diffusely while it gave minimal staining of cardiac muscle; the other reacting with myofibrils in Purkinje cells and heart. (3) Some sera with high titre smooth muscle antibodies (SMA) reacted with conducting tissue together with skeletal and cardiac muscle, suggesting that the four tissues have at least one antigen in common. (4) Known non-organ specific antibodies behaved as expected on beef conducting fibres: striational fluorescence of myasthenia gravis sera reacted with the same patterns on Purkinje myofibrils; AMA and ANA produced IFL in expected locations; ribosomal antibodies reacted strongly, while LKM and reticulin antibodies showed no reactivity. (5) Although the incidence of specific Purkinje fibre antibodies was not significantly raised in idiopathic heart block, the clinical associations suggest that some cases might be related to autoimmunity possibly involving cell-mediated mechanisms as in polymyositis.     

Leukocyte extravasation as a target for anti-inflammatory therapy - Which molecule to choose?

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.