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The mechanism of damage to neutrophils in allergic reactions in tuberculosis.

Allergic vulnerability of neutrophils due to pulmonary antigen and tuberculin in tuberculosis is connected with the fact that the immunological conflict antigen-antibody takes place on the surface of leukocytes. These two effects have a similar mechanism. The tissue antigen or tuberculin adsorbed on the cell surface with the participation of the complement may react with the corresponding circulating antibodies, thus producing damage to neutrophils.

Absorption↗

Measurement of anti-factor IX IgG subclasses in haemophilia B patients who developed inhibitors with episodes of allergic reactions to factor IX concentrates.

We have established a simple enzyme-linked immunosorbent assay (ELISA) for the detection of anti-factor IX IgG subclasses in haemophilia B patients with inhibitors. The assay was performed using immobilized purified factor IX. Specific IgG subclasses were detected by peroxidase-conjugated anti-human IgG1,2,3 and 4. Ten plasma samples from 6 haemophilia B patients with inhibitors ranging from 1.0 to 253 Bethesda Units/ml were analyzed. All samples were positive for IgG4. Six out of 10 samples were positive only for IgG4. Three samples were positive for IgG2. Five of the 6 patients had previously had allergic reactions to factor IX concentrates. Three patients had allergic episodes within the past month. Three samples from these latter patients taken on the day when the allergy had occurred showed positive also for IgG1. In later samples, however, taken at 4 days and 4 weeks respectively from two of these same patients. IgG1 was not detected. In two of the five patients in whom allergic reactions had occurred more than one month previously IgG1 was not detected. The results suggested that allergic reactions in patients with haemophilia B treated with factor IX concentrates were associated with the development of the specific IgG1 subclass of antibody to factor IX.

Adolescent↗

Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets.

BACKGROUND: Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger. METHODS: After admission to our clinic, 11 children with a prolonged cow's milk (CM) elimination diet because of AEDS and sensitization underwent double-blind placebo-controlled food challenge (DBPCFC). Retrospectively, the exposure to CM, sensitization and reactions to accidental ingestion were carefully documented. The DBPCFC was used to evaluate the childrens' current status. RESULTS: Before the elimination period (median 2.3 years; started before the admission) all 11 children with AEDS were sensitized and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the mother) without the development of acute reactions. The diagnosis of CM allergy was not confirmed by DBPCFC previously. After elimination the AEDS had not improved, but nevertheless the diet was continued. During the elimination period, eight of 11 children developed severe acute allergic reactions to CM after accidental ingestion. In evaluation, in our clinic all 11 children experienced acute allergic reactions to CM during DBPCFC. CONCLUSION: There is a considerable chance of developing acute allergic reactions to CM after elimination in children with AEDS without previous problems after CM intake.

Age Distribution↗

Allergic reactions in man.

The general features of allergic drug reactions in man have recently been reviewed by Parker (85). By definition allergic drug reactions are produced by specific immunologic processes. Allergic drug reactions must be distinguished from adverse reactions due to overdosage, normal pharmacologic action, toxic metabolite formation, idiosyncrasy, nonspecific release of pharmacologic effector molecules, or drug interactions. The clinical manifestations of drug allergy are quite protean. In addition to classical manifestations of allergy such as serum sickness, anaphylaxis, contact dermatitis or urticaria, drug allergy may produce hemolytic anemia, thrombocytopenia, granulocytopenia, hepatitis, nephritis, pneumonitis, vasculitis, or neuritis where a single organ or cell type is affected. While many drugs produce reactions with suggestive of allergy, definitive experimental evidence either for or against mechanism is usually not available. Some of these reactions may involve allergic mediators released or produced nonimmunologically through pharmacologic, osmotic, or toxic effects on cells involved in immune inflammation (mast cells, basophils, phagocytes, and lymphocytes) or through nonspecific activation of effector molecules in extracellular fluid such as the complement proteins. Drugs may also induce the formation of autoantibodies through mechanisms that are largely obscure, but may in some instances involve the direct participation of the drug as a hapten and in other instances occur indirectly through a pharmacologic or toxic action on the cells responsible for immune homeostasis.

Agranulocytosis↗

[Acute non-allergic reaction after administration of penicillin as a factor in the occurrence of neurotic symptoms].

The effect of a acute non-allergic reaction occurring after injection of procaine penicillin on the occurrence of different neurotic symptoms is a subject of the paper. 31 clinical cases, in which during the penicillin treatment the said reaction took place, were analysed. It has been found that the most often found consequence of that treatment is conversive neurosis, and subsequently the hypochondriac syndrome. On an average an acute non-allergic reaction occurred after the sixth injection. In 94% of the patients the neurotic symptoms appeared immediately after the described reaction. A positive correlation between the patient's age and an intensity of the converse symptoms was found. The Hoigne'a syndrome was a strong mental trauma, and was treated as an allergic shock for all of the patients. The patients were afraid of the next injection and they all refused to give permission for the continuation of such treatment. Neurotic syndromes related to Hoigne's syndrome turned out to be prolonged with a tendency for relapses, and low susceptibility to different methods of treatment. The mechanism of non-allergic acute reaction after procaine penicillin and ways of its prevention are also discussed.

Adult↗

[Studies of the specificity of immediate allergic reactions to ampicillin].

Ampicillin belongs to the drugs causing most frequently IgE-dependent allergic reactions, but the current specificity of these reactions is poorly known. Some experimental data suggest that the side chain of ampicillin may induce synthesis of drug-specific IgE antibodies. In our study we have decided to explain the specificity of ampicillin-induced allergic reactions type I appearing in patients after drug administration. Thirty-eight subjects developing an immediate response after administration of ampicillin entered the study. In all the patients skin tests with penicillin, ampicillin and amoxicillin determinants were performed. We have observed positive skin tests results with penicillin determinants in 23 subjects, in 32 subjects with ampicillin and in 17 cases with amoxicillin. Only in three persons the results were positive exclusively to ampicillin. The results of our study indicate that in the Polish population ampicillin induces an immediate IgE response with variable degree of cross-reactivity to other tested drugs, and selective response to ampicillin is uncommon.

Adult↗

[Anti-allergic effects of (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046), a specific thromboxane (TX) A2 synthetase inhibitor: effect of OKY-046 on II-IV type allergic reactions].

We studied the effects of OKY-046 on types II, III and IV allergic reactions, as classified by Coombs and Gell. In Type II, OKY-046 at 30-100 mg/kg intraduodenally (i.d.) and at 1-30 mg/kg intravenously (i.v.) inhibited the bronchoconstriction in a dose-dependent manner after Forssman antigen injection. Aspirin (3 mg/kg, i.v.) also suppressed it. OKY-046 (30-100 mg/kg, i.d.) suppressed the increase of TXB2 level in the plasma in a dose-dependent manner. However, there was no effect of OKY-046 and aspirin on the decrease in complement activity (CH50), platelets and leukocytes. Additionally, OKY-046 (300 mg/kg, p.o.) prolonged the survival time following Forssman antigen injection. However, the immune hemolysis reaction was not prevented by OKY-046 (10(-6)-10(-3) M). FUT-175 protected against the Forssman shock at 1 mg/kg, i.v. and the in vitro immune hemolysis reaction at 10(-5) M. In Type III, OKY-046 (300 mg/kg, p.o.) significantly suppressed the direct passive Arthus reaction and immune complex nephritis in rats. There was no effect of OKY-046 on the delayed-type hypersensitive response to picryl chloride in mice. We think that OKY-046 should be a beneficial drug for the treatment of types II and III allergic reactions.

Acrylates↗

[Effects of MY-5116 on experimental animal models of type I-type IV allergic reactions and the formation of IgE antibody].

The effects of a new anti-allergic agent, MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylate, on experimental animal models of type I approximately type IV allergic reactions and the formation of IgE antibody were investigated. MY-5116 administered intraperitoneally at doses of 30 and 100 mg/kg suppressed significantly the homologous PCA in guinea pigs. MY-5116 administered intraperitoneally at the dose of 100 mg/kg also suppressed significantly the heterologous PCA in guinea pigs. MY-1250, the main active metabolite of MY-5116, showed no suppression on the Schultz-Dale reaction in guinea pigs, and MY-5116 showed no inhibition on the active systemic anaphylaxis in mice (type I). MY-5116 showed no inhibition on the reversed cutaneous anaphylaxis in rats (type II), the Forssman reaction in guinea pigs (type II), the Arthus reaction in mice (type III) and the delayed type hypersensitivity in mice (type IV). MY-5116 showed no suppression on the formation of IgE antibody in C3H/He and BALB/c mice and rats. From these results, it is concluded that MY-5116 selectively suppresses the experimental models of type I allergic reaction.

Anaphylaxis↗

Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo.

High-affinity IgE receptor (FcepsilonRI) cross-linking on mast cells (MCs) induces secretion of preformed allergy mediators (degranulation) and synthesis of lipid mediators and cytokines. Degranulation produces many symptoms of immediate-type allergic reactions and is modulated by adhesion to surfaces coated with specific extracellular matrix (ECM) proteins. The signals involved in this modulation are mostly unknown and their contribution to allergic reactions in vivo is unclear. Here we report the generation of monoclonal antibodies that potently suppress FcepsilonRI-induced degranulation, but not leukotriene synthesis. We identified the antibody target as the tetraspanin CD63. Tetraspanins are membrane molecules that form multimolecular complexes with a broad array of molecules including ECM protein-binding beta integrins. We found that anti-CD63 inhibits MC adhesion to fibronectin and vitronectin. Furthermore, anti-CD63 inhibits FcepsilonRI-mediated degranulation in cells adherent to those ECM proteins but not in nonadherent cells. Thus the inhibition of degranulation by anti-CD63 correlates with its effect on adhesion. In support of a mechanistic linkage between the two types of inhibition, anti-CD63 had no effect on FcepsilonRI-induced global tyrosine phosphorylation and calcium mobilization but impaired the Gab2-PI3K pathway that is known to be essential for both degranulation and adhesion. Finally, we showed that these antibodies inhibited FcepsilonRI-mediated allergic reactions in vivo. These properties raise the possibility that anti-CD63 could be used as therapeutic agents in MC-dependent diseases.

Adaptor Proteins, Signal Transducing↗

Possibility of allergic reaction to dentin primer--application on the skin of guinea pigs.

We studied the allergic reaction of guinea pigs to glyceryl methacrylate (GM), hydroxyethyl methacrylate (HEMA) and meso-erythritol methacrylate (EM), which are used as dentin primers. On the 18th day of the application test, when macroscopic investigation revealed an inflammatory reaction, the methacrylic acid-treated group showed marked eschar formation in comparison with the control group. In each of the dentin primer groups, a slight degree of skin redness was noted, but there were no serious symptoms. On the 25th day, the applications were resumed macroscopic inspection on the 32nd day found eschar in the methacrylic acid group only. Therefore, this experiment with dentin primers suggests a delayed allergic reaction. Local irritability test showed a more severe reaction than the application test. In this test, all experimental dentin primers and methacrylic solution promptly showed inflammation, and the chemical compound, methacrylic acid was a factor in inflammation.

Animals↗

Allergic reaction to platinum in silicone breast implants.

Platinum is used as a catalyst in the manufacture of silicone breast implants. Because platinum is recognized as a potent sensitizer in certain circumstances, some have expressed concern that women with silicone breast implants are exposed to platinum, which is causing allergic reactions. We searched the literature for information on the level of platinum in breast implants and reports of sensitization that clearly related to platinum in women with breast implants. We found no published report with convincing evidence that platinum causes allergic reactions in women with breast implants or that women with breast implants are any more likely to have allergic reactions than women without breast implants.

Breast Implants↗

[Fine structure of human nasal mucosa in acute allergic reaction (author's transl)].

The fine structure of the acute allergic reaction is described in the human nasal mucosa. Subsequent to intranasal allergic testing with positive reaction characteristic changes are seen after different time intervals: Massive transudation into the dilated intercellular spaces, loss of epithelial junctions, extrusion of epithelial cells into the nasal lumen; increase permeability of capillaries and venules with increase of fenestrations and pinocytotic vesicles, edema of the cytoplasm and dilatation of intercellular junctions in the endothelium. Characteristic for the later stages are pronounced lesions of the vessel walls with interruption of cell junctions interstitial edema. endothelial gaps and loss of endothelial cells. The endothelial basal membrane usually remains intact. The findings are compared with those described for the acute hyperergic reaction in animals and chronic allergic changes in the human nasal mucosa.

Acute Disease↗

IgE-mediated allergic reaction to hyaluronidase in paediatric oncological patients.

UNLABELLED: Hyaluronidase has been gaining increasing interest as a spreading factor for better penetration of chemotherapeutics into CNS tumours. Five out of 16 patients with CNS tumours treated with hyaluronidase in addition to chemotherapeutic agents developed symptoms of immediate type allergic reactions, therefore we sought to characterize the harmful allergenic proteins of the bovine testes hyaluronidase enzyme preparation (Neopermease). The role of specific IgE for the allergic reaction was investigated. Using an immunoblotting technique, we investigated sera from 16 children treated with Neopermease (5 of them having developed anaphylactic reactions), 5 patients with atopy (atopic eczema) with high total IgE levels and 4 healthy children. SDS-PAGE of hyaluronidase preparation Neopermease revealed two major bands at 73 and 41-43 kDa. In all 5 sera from patients with adverse reactions, binding of specific IgE antibodies to have 73 and 41-43 kDa bands was found. Two patients reacted with the 73 kDa band exclusively, two patients reacted with both bands, one patient displayed IgE only to the 41-43 kDa band. A specific inhibition of IgE-binding to both bands was achieved after preincubation of the sera in four out of five patients with partially purified bovine hyaluronidase. Furthermore preincubation with gelatin, a stabilising agent in the commercial extract, led to a partial inhibition in the sera of three patients. No specific IgE binding was detected either in the sera of atopic patients, or in the control group. CONCLUSION: IgE mediated allergic reactions to hyaluronidase may occur in paediatric oncological patients treated with hyaluronidase. Whether these children are sensitized by intravenous hyaluronidase treatment or by cross-reactivity of other preformed IgE antibodies, yet to be specified, remains to be elucidated.

Adolescent↗

Allergic reactions following first insect sting exposure.

Over a 10-year period, 750 patients were evaluated because of anaphylaxis following insect stings. Sixty-five patients were identified who had reactions after their first sting exposure. Their clinical features and symptoms of anaphylaxis were the same as the much larger group of patients who had allergic reactions following prior exposure to insect stings. When evaluated following the sting reaction, the majority of these patients had venom-specific IgE detected by skin test or in the serum by the RAST. Fifty-three re-stings occurred in 31 patients. In untreated or whole body extract-treated patients, there were 43 re-stings resulting in 13 reactions. There were no reactions following 10 re-stings in venom-treated patients. In a subgroup of 15 patients with undetectable venom-specific IgE, there were 16 re-stings in eight patients, leading to three systemic reactions. The occurrence of allergic reactions following first sting exposure adds further support to the thesis that some sting reactions are non-IgE-mediated.

Adolescent↗

The kiss of death: a severe allergic reaction to a shellfish induced by a good-night kiss.

True (IgE-mediated) allergic reactions to crustaceans are relatively common and can be serious. A young woman with a clinical history of multiple urticarial reactions after touching shrimp and lobster dishes was seen in an emergency department of a Mayo Clinic-affiliated hospital for an anaphylactic reaction that developed immediately after she kissed her boyfriend. The boyfriend had eaten several shrimp just before the kiss. It is important to warn susceptible patients that food does not actually have to be eaten to trigger an allergic reaction; touching the offending food and kissing or touching someone who has recently eaten the food can be enough to cause a major reaction.

Adult↗

Involvement of eosinophils in the early-phase allergic reaction in a guinea pig rhinitis model.

BACKGROUND: Eosinophils are found in the nasal lavage fluid (NLF) and nasal biopsies of patients with allergic rhinitis after a nasal antigen challenge, and associated not only with a late-phase allergic reaction (LPR) but also an early phase allergic reaction (EPR). Numerous studies have been carried out to clarify the participation of eosinophils in LPR or airway hyperresponsiveness. However, there has been no published report describing in detail the role of eosinophils during EPR. To better understand the involvement of eosinophils in EPR, we studied the effects of repeated antigen challenges on nasal airway responsiveness and eosinophilic inflammation in EPR using a guinea pig rhinitis model. METHODS: Nasal airway responsiveness was measured as the nasal airway resistance (NAR) after nasal antigen provocation. Eosinophilic inflammation during EPR was assessed by nasal lavage and histopathological examination using two groups of animals: those in group 1 were subjected to a sensitization pretreatment only, and those in group 2 were subjected to a pretreatment of sensitization followed by repeated nasal challenges. RESULTS: Repeated antigen challenges induced nasal hyperresponsiveness as indicated by a decrease in the antigen provocation dose and a significant increase in NAR. Furthermore, significant increases in eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in NLF during EPR were observed following antigen provocation in group 2. There were significant correlations between the levels of these parameters, and albumin was the most prevalent of the proteins in NLF. Histopathological examination showed that the degree of eosinophil infiltration into the lamina propria of the nasal mucosa of the animals in group 2 was significantly and apparently higher than in group 1. Particularly, epithelial disruption and mucosal edema were significantly elevated after antigen provocation in group 2. CONCLUSIONS: These results suggest that chronic eosinophil accumulation is induced by repeated antigen challenges in the nasal tissue, and that once antigen provocation occurs, eosinophils in the tissue are activated and responsible for the amplification of EPR such as vascular permeability and mucosal edema.

Animals↗

Effects of fujibitol, a remedy for nasal symptoms of immediate and delayed type allergic reactions.

The effects of Fujibitol, a remedy for the nasal symptoms of immediate and delayed type allergic reactions were studied. Fujibitol inhibited active systemic anaphylaxis in mice, heterologous passive cutaneous anaphylaxis (PCA) in rats, Masugi's nephritis in rats and delayed type hypersensitivity induced by picryl chloride in mice, but did not affect homologous PCA or immune complex-induced glomerulonephritis in rats. These results suggested that Fujibitol is effective for treatment of allergy-induced inflammation since IgG and type IV allergic reactions were inhibited.

Anaphylaxis↗

Delayed type allergic reaction following the use of nonlatex rubber dam during endodontic treatment.

AIM: To describe the development of a delayed type allergic reaction 24 h following the use of nonlatex rubber dam during endodontic treatment. The symptoms were alleviated with adequate medication; however, the patient rejected any further analysis. SUMMARY: In recent years, allergic reactions because of latex rubber dam and gloves have received more attention. Nonlatex products are advocated in clinical use in cases where the patient presents an allergic background. Although rare, adverse reactions may be encountered even with these products. In this article, a very rare case is presented in which a patient developed signs of allergy 24 h after the utilization of nonlatex rubber dam and gloves during endodontic treatment. Signs including visible redness on the mucosa, submucosal oedema and desquamation in the vestibular mucosa were observed. With proper medication, the signs and symptoms were alleviated. Although the patient was referred to an allergy specialist for patch testing, she did not accept any further analysis. KEY LEARNING POINTS: This case emphasizes the necessity of precautions during the management of latex-allergic patients in clinical practice. The unusual response encountered in this patient does not undermine the usefulness of nonlatex rubber dam and gloves in sensitive individuals.

Dermatitis, Allergic Contact↗