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Our experience with acetylsalicylic acid hypersensitivity.

Results of a study carried out in 21 patients with acetylsalicylic acid (Aspirin), hypersensitivity, 17 females and 4 males, aged 16 to 69 years (mean 45.7) are presented. Some patients suffered from several types of allergic symptoms - 11 from Asthma, 3 Rhinitis, 3 Quinke edema, 5 Urticaria and 2 Anaphylactic Shock. Concomitant drug allergies, route of administration and composition of the ingested drug, familiar complaints of drug allergy, nasopharyngeal examination and lung function by spirometry and Acetylcholine tests were evaluated. Blood, sputum and nasal mucous eosinophil count, as well as secretory IgA and its secretory piece identification in saliva and nasal mucous, serotonin and histaminopexic power of serum and immunoelectrophoresis of serum proteins were performed in all patients. Human basophil degranulation test to Aspirin were evaluated in 12 patients. Skin prick tests with one standard range of 21 common allergens were done in all patients and intradermal skin tests with 1 lysine acetyl-salicylate (1/100 and 1/1000) were performed in all patients as well as in a selected control group of 12 healthy subjects.

Adolescent↗

[Anaphylaxis caused by omeprazole].

Omeprazole is a proton pump inhibitor which reduces both basal and stimulated gastric acid secretion by inhibiting the parietal cell enzyme H(+)-K(+)-adenosine triphosphatase. Typical adverse effects of proton pump inhibitors are nausea, diarrhea, constipation and endocrinologic abnormalities such as gynecomastia. Cutaneous side effects are rare but may include contact dermatitis, lichenoid eruption, leukocytoclastic vasculitis or toxic epidermal necrolysis; anaphylaxis is rare. We identified omeprazole as the causative agent by oral challenge test in a patient who had developed anaphylaxis while taking several drugs.

Anaphylaxis↗

CD63 expression on basophils as a tool for the diagnosis of pollen-associated food allergy: sensitivity and specificity.

BACKGROUND: Basophil activation is associated with the expression of CD63. Because allergens can induce basophil activation by cross-linking specific IgE, increased CD63 expression has been proposed as a novel in vitro test for immediate type allergy. OBJECTIVE: We compared the CD63-based basophil activation test (BAT) in the diagnosis of allergy to carrot, celery and hazelnut with skin prick tests (SPT) and measurement of allergen-specific IgE. METHODS: Twenty-nine patients with a history of an oral allergy syndrome induced by carrot, celery or hazelnut (n = 20 for each allergen) and 20 controls were studied. SPT were performed with standardized and native carrot, celery and hazelnut extracts. Allergen-specific IgE was determined by the CAP FEIA method and basophil activation was determined by flow cytometry upon double staining with anti-IgE/anti-CD63 mAb. RESULTS: SPT with native carrot, celery and hazelnut showed sensitivities of 100%, 100% and 90%, and specificities of 80%, 80% and 90%. SPT with commercial extracts of the same allergens gave sensitivities of 85%, 80% and 85%, and specificities of 80%, 80% and 90%. Sensitivity of allergen-specific IgE and the BAT for carrot, celery and hazelnut was 80% vs. 85%, 70% vs. 85%, and 80% vs. 90%, with corresponding specificities of 80% vs. 85%, 80% vs. 80%, and 95% vs. 90%. The cut-off for a positive BAT was 10% CD63+ basophils. Moreover, there was a positive correlation between IgE reactivity and the number of CD63+ basophils for all food allergens (carrot: r = 0.69, celery: r = 0.67, hazelnut: r = 0.66). CONCLUSIONS: Quantification of basophil activation by CD63 expression is a valuable new in vitro method for diagnosis of immediate type food sensitization. Although double-blind placebo-controlled food challenges remain the gold standard, the CD63-based BAT may supplement routine diagnostic tests such as SPT or allergen-specific IgE in the future.

Antigens, CD↗

Ethylene oxide (ETO) as a major cause of anaphylactoid reactions in dialysis (a review).

Ethylene oxide (ETO), an alkylating compound of high chemical reactivity, is widely used for gas sterilization, but recently serious ETO side reactions have been recognized. With chronic ETO exposure, increased spontaneous abortion, sister chromatid exchange, and leukemia are observed. After medical use of ETO outside nephrology, contact dermatitis, cardiopulmonary shock (during cardiopulmonary surgery), allergic local reactions to ETO sterilized lenses, and anaphylactoid reactions to ETO sterilized catheters have been described. In numerous dialysis patients widespread hypersensitivity to ETO has been documented by skin prick test and ETO radioallergosorbent test (RAST). Furthermore an anaphylactoid "first-use reaction" was described in dialyzed patients, most of whom were using hollow-fiber dialyzers. After long discussions whether complement activation versus hypersensitivity is the cause of such acute anaphylactoid reactions, more recent studies using either ETO RAST or basophil degranulation tests implicate ETO hypersensitivity as their major cause. The high prevalence of sensitization to ETO and the frequency, unpredictability, and potential danger of anaphylactoid reactions to ETO lead to the conclusion that ETO sterilization of dialyzers should be discontinued, since alternative modalities of sterilization are currently available.

Anaphylaxis↗

[Circulating and basophil-fixed specific IgE in human alveolar echinococcosis].

Biological parameters of immediate type hypersensitivity were assessed in 19 patients with alveolar echinococcosis. Serum total IgE concentrations were higher than normal values in 12 patients, and parasite-specific IgE were present in 9 patients. A significant relationship was observed between these two parameters. Evolution of specific IgE during a 1-year period appeared to correlate with surgical removal of parasitic material; it did not correlate with the clinical evolution in patients treated with mebendazole. Specific basophil fixed-IgE were demonstrated using both a basophil degranulation test and a histamine release test in the 19 patients under study, including serologically negative and circulating specific IgE-negative patients.

Basophils↗

Evidence of sensitized basophils in renal transplanted patients.

The participation of basophil polymorphonuclear leukocytes in the response to kidney allografts in man has hardly been studied. In 23 patients, followed from the immediate post-transplant period for several years, the number of circulating basophils, expressed either as absolute number or as percentage of leukocytes, was significantly low in relation to that of controls. IgE on the basophil surface was determined by radioimmunoassay in 14 patients. All patients but one had elevated numbers of IgE molecules per basophil, values being higher in patients with cadaver grafts and in patients with a graft functioning at 6 months or less. When the count of circulating basophils was roughly normal, six of the eight patients showed a positive basophil degranulation test against the donor lymphocytes. These results suggest the existence of specific IgE antibodies for HLA antigens in renal transplanted patients.

Basophils↗

Marked improvement of the basophil activation test by detecting CD203c instead of CD63.

BACKGROUND: The flow cytometric basophil activation test by detection of CD63 expression has been developed as an alternative method for in vitro diagnosis of IgE-mediated reactions to various allergens. Despite promising initial studies, the test remains disappointing in terms of sensitivity. CD203c has recently been demonstrated as a specific activation marker of basophils that is rapidly up-regulated after allergen challenge in sensitized patients. OBJECTIVE: The goal of the present study was to compare basophil activation tests by using either CD203c or CD63 in the diagnosis of immediate-type allergy to latex. METHODS: Twenty-seven patients (health care workers of our institution) who developed clinical features evocative of allergy after contact with latex were included and classified into two groups. Group 1 (n = 16) comprised true allergic patients who presented with typical signs of immediate allergic reaction associated with a positive skin test (prick test). Group 2 (n = 11) consisted of patients whose clinical history was not typical and had negative skin test. Twelve healthy subjects were also studied as controls. We compared the sensitivity of two triple-staining flow cytometric protocols measuring basophil activation after latex stimulation: CD45-IgE-CD63 and CD45-IgE-CD203c. RESULTS: The CD203c protocol showed a higher sensitivity than the CD63 protocol (75% vs. 50%). In comparison, latex-specific IgE sensitivity was found to be 69%. Furthermore, the magnitude of the basophil response was significantly higher with CD203c in comparison with CD63. Specificity was 100% for both protocols. CONCLUSION: Due to superior gating of basophils and a higher range of activation in response to allergen, the basophil activation test is markedly improved by use of CD203c instead of CD63.

Adult↗

In vitro ketotifen protection in bronchial hyperreactivity.

There are drugs, such as ketotifen, that inhibit bronchospasm through different mechanisms. In this study, we looked at the changes in the number of sanguineous cells that ketotifen produces, especially in basophil cells, that could explain its prophylactic effects in bronchial hyperreactivity disclosed by exercise, as well as its relation to the variations in basal and total histamine in blood. 22 patients were selected, with a diagnosis of extrinsic bronchial asthma with sensitization against Dermatophagoides, and were compared to a control group. They all underwent an exercise test. Blood samples were taken before and after exercise in order to measure the number of leukocytes and the changes in basal and total histamine. We found that the number of basophils does not increase after exercise in untreated patients, while it does in the control group and in treated patients. This implies that ketotifen stabilizes the basophil cells, hindering their degranulation and the subsequent liberation of mediators that would produce bronchospasm after exercise.

Adolescent↗

The flow-cytometric determination of basophil activation induced by aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) is useful for in vitro diagnosis of the NSAID hypersensitivity syndrome.

BACKGROUND: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs), manifested by cutaneous symptoms and/or airway manifestations represent 20-25% of all hypersensitivity reactions to drugs. Today, it is still claimed that no in vitro diagnostic tests exist for that condition and that the only way to confirm the diagnosis is a provocation challenge. OBJECTIVE: The objective of this study was to assess whether NSAIDs may provoke blood basophil activation in vitro in such patients, as detected by a flowcytometric technique. METHODS: Sixty NSAID hypersensitive patients (38 with cutaneous, 20 with airway and two with cutaneous and airway symptoms) and 30 control patients (15 asthmatics) were selected. Their hypersensitivity was confirmed by documented history indicating at least two clinical episodes to two or more different NSAIDs or by positive oral provocation challenge. Isolated buffy coat leukocytes were stimulated in vitro with aspirin, paracetamol, metamizol, diclofenac, and naproxen. The percentage of activated basophils was evaluated by an anti-CD63. RESULTS: Aspirin showed a sensitivity of 43.3%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.4%. For the other NSAIDs, the sensitivity and specificity values were: for paracetamol 11.7% and 100%, for metamizol 15% and 100%, for diclofenac 43.3% and 93.3% and for naproxen 54.8% and 74.1%. When considering the first four NSAIDs, the global sensitivity raised to 63.3% and specificity to 93.3%. If the number of tests is to be limited for practical reasons, the combination of acetylsalicylic acid and diclofenac at two concentrations yields a sensitivity of 58.3% and a specificity of 93.3%. CONCLUSIONS: Flowcytometric determinations of basophil activation following stimulation with NSAIDs show a high sensitivity (60-70%) with specificity above 90%. So this test may help avoiding some cumbersome and dangerous provocation challenges.

Acetaminophen↗

Allergen dependent production of histamine releasing actor by alveolar macrophages.

Human Basophil Degranulation Test (HBDT) has been employed for the research of Histamine Releasing Factor (HRF) from macrophages in asthma. Macrophages have been obtained from broncho-alveolar lavages, incubated with specific allergens and the products of this stimulation added to HBDT preparations. The production of an active HRF has been observed only in macrophages from atopic patients. The effect of this HRF seems to be IgE dependent, the degranulation of human basophils being in general significant only for basophils of atopic patients.

Allergens↗

[Anaphylactoid accidents during general anesthesia. Apropos of 55 cases].

Analysis of fifty-five anaphylactoid accidents during general anesthesia (GA) in fifty patients shows significant female predominance (70%), relatively frequent allergic predisposition (34% as compared to 14.3% in a normal population) and fairly frequent responsibility of suxamethonium and succinylcholine. One or more, even recent, previous GAs do not seem to enhance the risk. 50% of intradermal skin tests to different anesthetics were negative, 40% were positive and consistent with clinical history, and 10% were positive but inconsistent clinically. Biological tests (basophil degranulation, lymphoblast rosettes, in vitro consumption of complement) were negative. Physiopathological mechanisms remain uncertain, whether they involve IgE allergy or complement activation. The frequency and severity of these unpredictable accidents must stimulate clinical and biological research in this field.

Adult↗

Allergen-induced basophil activation: CD63 cell expression detected by flow cytometry in patients allergic to Dermatophagoides pteronyssinus and Lolium perenne.

BACKGROUND: In this study, we determined by flow cytometry the percentage of basophils activated after in vitro stimulation by allergens and expressing the CD63 marker. The diagnostic reliability of the technique was assessed as well as its correlation with other in vitro diagnostic parameters. METHODS: Fifty-three patients suffering from asthma and/or allergic rhinitis following sensitization to Dermatophagoides pteronyssinus and 51 patients sensitized to Lolium perenne were investigated. Twenty-four atopic patients not sensitive to these allergens and 38 healthy subjects were also selected as controls. The basophil activation test determines the percentage of basophils which express CD63 as an activation marker, by means of flow cytometry, after in vitro stimulation with allergen, using double labelling with monoclonal antibody anti-CD63-PE and anti-IgE-FITC. RESULTS: No differences in basal values (non-activated control) were found between sensitized patients, atopic controls and healthy controls. On the other hand, sensitized patients showed a significantly higher percentage of activated basophils after stimulation by allergens in vitro than both control groups (P < 0.001). We found a significant correlation between skin tests and basophil activation tests (r = 0.72, P < 0.001). We also found a positive and significant correlation between basophil activation tests and histamine release tests (r = 0.80, P < 0.001), allergen-specific sulphidoleukotriene production (r = 0.7, P < 0.001) and the occurrence of serum allergen-specific IgE (r = 0.71, P < 0.001). CONCLUSION: The basophil activation test is a highly reliable technique in the diagnosis of allergy to inhalant allergens. The sensitivity of the basophil activation test was 93.3%, and its specificity 98.4%, when using a cut-off point of 15% activated basophils as positive result.

Adult↗

[Anaphylaxis caused by lidocaine].

A case of a severe anaphylactic reaction in a 30 year old man after 2 ml of 1% lidocaine injected subcutaneously is reported. It consisted in pruritus, urticaria, hypotension (Pasys: 50 mmHg), tachycardia (170 b.min-1) and a coma of short duration. The patient recovered after 1 mg adrenaline injected subcutaneously. The patient's history included a less severe but similar accident, but no manifestations of atopy. The total IgE, two months after the accident, were at the upper limit of normal. A human basophil degranulation test was positive for lidocaine and negative for other amide local anaesthetic agents and preservatives. Similarly, lidocaine was the only molecule giving a positive reaction with intradermal testing. Skin sensitivity to histamine was negative. Although for several authors true allergy to lidocaine is questionable, the case reported here can be added to the other 47 published since 1961.

Adult↗

[A technic for human basophil degranulation].

We had studied the human basophil degranulation test (HBDT) in 26 cases of allergic patients with drugs (penicillin, erythromycin, josamycin) one month after their anaphylactic reaction. This test was negative in 7 cases on 8 for penicillin, positive in 8 cases on 10 for erythromycin and in 6 cases on 8 for josamycin. The failure of this test with penicillin can be explained by a sensitization to a metabolic penicillin product or to the complex hapten-carrier.

Basophils↗

Fractionation and biological characterization of Olea europea pollen extract.

Preliminary fractionation of Olea european pollen extract has been performed. At least 10 antigenic fractions have been found by crossed electrophoresis. After Sephadex gel filtration, two fractions with a molecular weight of 160,000 and 65,000 have been obtained. The fractions were evaluated for allergenic activity by two in vitro techniques: polystyrene tube radioimmunoassay (PTRIA) and basophil degranulation test (BDT), and by skin tests. All tests indicated that the most reactive fractions were those in the 65,000 molecular weight peak. BDT has been shown to be a very reliable method as compared with histamine release and other parameters. Although common antigenic fractions have been found for Lollium perenne and O. europea, no cross-allergenicity has been shown by PTRIA inhibition.

Basophils↗

Anaphylaxis to Gelofusine confirmed by in vitro basophil activation test: a case series.

The plasma expander Gelofusine (succinylated gelatin) is a recognised cause of peri-operative anaphylaxis. Current diagnosis of Gelofusine sensitivity is by skin testing, a procedure that itself carries a risk of allergic reaction. We evaluated the reliability of the in vitro basophil activation test as a diagnostic assay for Gelofusine sensitivity in subjects with a clinical history highly suggestive of Gelofusine allergy. Six patients with peri-operative anaphylaxis clinically attributed to Gelofusine were skin tested to confirm sensitivity. Control subjects included three healthy subjects and five subjects allergic to a neuromuscular blocking drug, all negative on Gelofusine skin testing. Whole blood basophil activation to Gelofusine was analysed by flow cytometry for CD63 surface expression. All of the Gelofusine sensitive patients and one of the control allergic subjects showed positive basophil activation to Gelofusine. In this series of subjects, the basophil activation test for Gelofusine allergy had a sensitivity of 100% and a specificity of 87.5%. Our findings suggest that basophil activation testing is a safe and reliable in vitro assay for prediction or confirmation of Gelofusine sensitivity in patients with high clinical suspicion of Gelofusine-induced anaphylaxis.

Aged↗

Basophil sensitization for food allergens in idiopathic nephrotic syndrome.

To estimate food sensitization, the human basophil degranulation test (HBDT), usually used for allergy diagnosis, was performed in 34 idiopathic nephrotic syndrome (INS) patients, classified as minimal change glomerular disease, with or without atopic manifestations, and in 19 blood donors; five food allergens (wheat flour, cow's milk, whole egg, beef and pork) were investigated. The HBDT was positive in 22 out of the 34 INS (64%) and in 1 out of the 19 blood donors (p less than 0.001). The test was 9 times positive for wheat flour, 9 times for pork, 6 times for cow's milk, 6 times for beef and 5 times for whole egg. Moreover in 13 cases, the basophil sensitization was present for two or three of these food allergens in the same patient. A direct causal relationship between food sensitization and INS cannot be drawn from this study: it might be demonstrated only by elemental or oligoantigenic diet prior to specific avoidances.

Allergens↗