Jgr Demonchy

ANAPHYLACTOID SHOCK FOLLOWING HYMENOPTERA STING AS A PRESENTING SYMPTOM OF SYSTEMIC MASTOCYTOSIS

Abstract. Systemic mastocytosis is a rare and chronic disorder characterized by a pathologically increased number of mast cells in various tissues and overproduction of mast cell mediators. From a group of 15 patients (10 females. 5 males) with systemic mastocytosis five female patients presented with a history of an anaphylactoid shock reaction to wasp sting. Three of them had no demonstrable specific IgE against wasp or bee venom in serum, and a skin test that was only weakly positive for wasp venom. One patient had specific IgE against wasp venom and a clearly positive skin test to wasp venom. The other patient had specific IgE against both wasp and bee venom and a skin test that was only weakly positive to wasp venom. Two patients had to stop a hyposensitization procedure because of systemic side effects. The five patients did not differ from the other patients with systemic mastocytosis with regard to either clinical symptoms and signs or urinary excretion of histamine metabolites. From the latter group two female and three male patients said they had been stung by a wasp in the past. Thus, anaphylactoid shock after Hymenoptera sting can be a presenting symptom of systemic mastocytosis and may be caused by an IgE‐as well as a non‐IgE‐mediated mechanism. In cases of anaphylactoid reaction to Hymenoptera sting, especially when there is no IgE demonstrable in serum or in cases of intolerance of hyposensitization, the diagnosis of systemic mastocytosis should be considered, also in the absence of the clinical hallmarks of urticaria pigmentosa.

The allergenic and antigenic properties of spore extracts of Aspergillus fumigatus: A comparative study of spore extracts with mycelium and culture filtrate extracts

The antigenic properties of conidial preparations of Aspergillus fumigatus were compared with mycelial and culture filtrate extracts by use of sera of patients with aspergillosis and hyperimmune rabbit serum. Biologic activities were tested by intracutaneous tests. The immunologic parameters used were: precipitating properties in double-diffusion, IgG binding by ELISA, IgE binding by enzyme inhibition assay, and by enzyme allergosorbent test. It has been demonstrated that the components that are released after disintegration of spores have positive titers in all immunologic assays. The immunologic properties of these spore plasma extracts are comparable with mycelial and/or culture filtrate extracts that are in accordance with the corresponding skin reactivities. Components that are released spontaneously from spores are only weakly positive or negative in the immunologic assays and demonstrate a very low biologic activity.

Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways obstruction and hyperresponsiveness

Although home recording of peak expiratory flow (PEF) is considered useful in managing asthma, little is known about the relationship of PEF variation to other indicators of disease activity. We examined the relationship of PEF variation, expressed in various ways, to symptoms, atopy, level of lung function, and airways hyperresponsiveness in schoolchildren with asthma. One hundred and two asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a diary for 2 weeks after withdrawal of all anti-inflammatory maintenance medication. PEF variation was expressed as amplitude % mean, as standard deviation and coefficient of variation of all recordings, and as low % best (lowest PEF as percentage of the highest of all values). Atopy and level of forced expiratory volume in one second (FEV1) % predicted were not significantly related to PEF variation. The provocative dose of histamine causing a 20% fall in FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF variation. The index, low % best, proved easy to calculate and effective in identifying a short-term episode of reduced PEF. We conclude that peak expiratory flow variation in children with stable, moderately severe asthma is significantly, but weakly, related to symptoms and airways hyperresponsiveness. These three phenomena, therefore, all provide different information on the actual disease state. Expressing peak expiratory flow variation as low % best is easy to perform and appears to be clinically relevant.

MEASUREMENT OF N-TAU-METHYLHISTAMINE CONCENTRATIONS IN PLASMA AND URINE AS A PARAMETER FOR HISTAMINE-RELEASE DURING ANAPHYLACTOID REACTIONS

Nτ-methylhistamine concentrations in plasma and urine were determined using a newly developed simultaneous determination for histamine andNτ-methylhistamine, based on isotope dilution mass fragmentography. Three groups of patients were investigated: patients receiving intravenously-administered iodamide for excretory urography, patients receiving a wasp-sting challenge, and patients treated with an intravenously-administered muscle relaxant. In all patients showing a distinct systemic anaphylactic or anaphylactoid reaction histamine andNτ-methylhistamine concentrations were found to be elevated. From the results of this study it can be concluded thatNτ-methylhistamine in plasma and urine is a good parameter for histamine release, and that the determination of this histamine metabolite are less hampered by possible artefacts (due to basophil disrupture, a very short half-life time or bacterial production) than determinations of histamine itself.

DETERMINATION OF NTAU-METHYLIMIDAZOLEACETIC ACID (A HISTAMINE METABOLITE) IN URINE BY GAS-CHROMATOGRAPHY USING NITROGEN-PHOSPHORUS DETECTION

N tau-Methylimidazoleacetic acid, the quantitatively most important metabolite of histamine, was isolated from urine by ion exchange chromatography. After esterification with 2-propanol and extraction, N tao-methylimidazoleacetic acid was analyzed by capillary gas chromatography with nitrogen-phosphorus detection, using N tao-ethylimidazoleacetic acid as internal standard. The synthesis of this internal standard is described. In contrast to the methods hitherto described, this method is appropriate for use in clinical chemical laboratories. Normal 24-h excretion ranged from 8.3 to 18.5 mumol (n = 20). Five patients with mastocytosis, a patient with chronic myelocytic leukemia and a patient after an anaphylactoid reaction on acetylsalicylic acid showed highly elevated values.

HISTAMINE IN LATE ASTHMATIC REACTIONS FOLLOWING HOUSE-DUST MITE INHALATION

In order to investigate the role of histamine in the late asthmatic reaction (LAR) following house-dust mite (HDM) inhalation, we studied, with hourly intervals, urinaryNτ-methylhistamine (an important metabolite of histamine) in 14 allergic asthmatic patients before and after broncho provocation with HDM.Four patients showed an early asthmatic reaction (EAR), while 10 patients developed a LAR as well. In the hour following the EAR a significant increase in urinaryNτ-methylhistamine was observed as compared to the control day (0.01<p<0.05). During the LAR no increase of this metabolite was detected in the urine of the patients. Additionally, histamine was measured in broncho alveolar lavage fluid (BAF) obtained from 6 patients during the HDM-provoked LAR and compared to histamine levels in BAF from patients without a LAR, following broncho provocation.In the LAR group higher histamine levels were found than in the other patient and control groups. For the whole patient group no correlation was found between the degree of bronchial obstruction during the LAR and the BAF histamine values. No difference was found inNτ-methylhistamine in BAF between patients with LAR and controls. Thus histamine metabolite studies in the urine failed to provide evidence of involvement of histamine in the LAR, while further data are needed to interpret the results of local sampling in the lung.

Immunologic studies in bronchoalveolar fluid in a patient with allergic bronchopulmonary aspergillosis

Bronchoalveolar lavage was performed in a patient during an acute stage of allergic bronchopulmonary aspergillosis (ABPA) and repeated 17 mo later during a remission stage and cessation of corticosteroid therapy. Measurement of protein concentrations (albumin, IgG, IgA, and IgM) by laser nephelometry and crossed immunoelectrophoresis indicates that transudation of proteins occurs from the circulation into the lung compartment during the acute stage of ABPA. Furthermore, comparing total Ig concentrations and titers of ELISA IgG, IgA, and IgM antibodies against Aspergillus fumigatus with the corresponding values of serum measurements indicates a preferential local production of IgA antibodies and IgM to a lesser extent. No indications were found for a local production of either IgG, total IgE, or IgE against A. fumigatus. During remission of the ABPA, titers of antibodies in the bronchoalveolar fluid (BAF) decreased to normal levels except IgA against A. fumigatus that remained elevated. The elevated titers of IgA in the BAF and IgE antibodies in the serum against A. fumigatus together with the elevated numbers of granulocytes in the BAF during the remission stage indicate that the immunologic situation is not yet normalized.

INCREASED URINARY-EXCRETION OF THE HISTAMINE METABOLITE N-TAU-METHYLHISTAMINE DURING ACETYLSALICYLIC-ACID PROVOCATION IN CHRONIC URTICARIA PATIENTS

Seventeen chronic urticaria patients with a history suggestive of acetylsalicylic acid (ASA, Aspirin)-intolerance were challenged with ASA; only 2 patients showed marked clinical reactions. These clinical reactions were accompanied by a significant increase in the urinary excretion of the most important histamine metabolite, Nι-methylhistamine, in comparison with 15 non-responders (p≤0.05) and placebo test. These results suggest an involvement of histamine in the pathogenesis of ASA-intolerance in chronic urticaria patients.

Effects of isoprenaline and terbutaline on urinary excretion of histamine and its two main metabolites in systemic mastocytosis

Both short-term and long-term effects of the β-sympathomimetic drugs isoprenaline and terbutaline on the urinary excretion of histamine and its two main metabolites were evaluated in patients with systemic mastocytosis.In a short-term study isoprenaline and terbutaline were given intravenously during five hours to three and two patients, respectively. Compared with placebo infusion Nt-methyl-histamine excretion fell during terbutaline administration, whereas during isoprenaline no changes were observed.In a long-term study three patients received a treatment with orally administered terbutaline for 24 days. In one patient a slight reduction of the excretion of the histamine metabolites was found. In another patient the excretion of histamine and its metabolites, decreased especially during the eight days observation period after the end of the treatment. In this study we saw occasionally large and rapid changes occurring simultaneously in all three urinary parameters of histamine release.In conclusion, terbutaline can reduce histamine release in systemic mastocytosis. However, because of the small symptomatic and biochemical effects found in our patients, the clinical significance of β-sympathomimetic drug treatment in this disease has yet to be established.