Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity.

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P < 0.001) or MAT 10/22 (46%, P < 0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls.

Differentiating the cellular and humoral components of neuromuscular blocking agent-induced anaphylactic reactions in patients undergoing anaesthesia.

BACKGROUND: The significance of IgE antibodies to neuromuscular blocking agent (NMBA)-induced anaphylactic reactions during anaesthesia is unclear. We investigated the relevance of IgE to rocuronium using an in vitro technique. METHODS: Serum samples from 61 patients with anaphylactic reactions during anaesthesia were investigated. On the basis of clinical history, allergy to NMBA was considered likely in 48 patients, further assessed using intradermal skin tests for several commonly used NMBAs, including rocuronium, vecuronium, and succinylcholine. To determine the presence of rocuronium IgE in human serum, a rocuronium-human serum albumin (rocHSA) conjugate was coupled to a solid phase and a radioallergosorbent test performed. The biological effects of patient serum NMBA-IgE on histamine release were investigated using in vitro sensitized basophils from healthy blood donors. RESULTS: IgE to rocuronium was found in 23 of 48 serum samples (48%) with NMBA allergy, although only two of these were able to sensitize basophils to release histamine in response to rocHSA. IgE-responsiveness in the basophil test was only observed with conjugated rocHSA and not with unconjugated rocuronium or the other NMBAs evaluated. However, unconjugated rocuronium inhibited the histamine release induced by rocHSA. Correlation between skin-test reactivity to rocuronium and IgE to rocHSA was low (P>0.1). In contrast, striking correlation between IgE to rocuronium and skin-test reactivity to succinylcholine was found (P<0.001). CONCLUSIONS: Our results indicate that NMBA-related anaphylaxis requires not only IgE NMBA reactivity, but also altered cellular reactivity in the patient. The latter may be demonstrable by testing basophils from the patient, a skin test with (steroidal) NMBA, or both.

[Safety of reintroducing platelet-inhibitory doses of aspirin in patients with urticaria or angioedema induced by anti-inflammatory doses]. / Réintroduction de l'aspirine à dose antiagrégante après urticaire ou angio-oedème induits par des doses anti-inflammatoires.

BACKGROUND: Aspirin is one of the most widely prescribed drugs in the world on account of its analgesic, antipyretic, and anti-inflammatory properties. Its effect on platelet aggregation makes it the first choice for prophylaxis in cardiovascular, neurological and obstetric diseases. However, a history of aspirin-induced urticaria and/or angioedema is usually a contraindication for further prescription of the drug. The aim of this article was to demonstrate that patients presenting aspirin-induced cutaneous reactions at anti-inflammatory doses can safely benefit from aspirin reintroduction at platelet-inhibitory doses. PATIENTS AND METHODS: Patients with a history of aspirin-induced urticaria and/or angioedema referred to our department between January 2000 and June 2008 for double-blind placebo-controlled reintroduction at platelet-inhibitory doses for a medical indication were enrolled in this study. RESULTS: Seventy patients with aspirin hypersensitivity as well as a medical indication for this therapy were referred to our department. Of these, 38 (54.3%) had a history of aspirin-induced urticaria and/or angioedema, including three laryngeal oedemas (7.9%). All subjects received platelet-inhibitory doses of aspirin (maximal total dose: 400mg/day) in double-blind placebo-controlled fashion during a one-day hospitalization period. None of the patients presented an immediate hypersensitivity reaction. Only one patient, who had received a cumulative dose of 200mg/day, reported diffuse urticaria and facial angioedema of no clinical significance the following day. He had a history of chronic urticaria. CONCLUSION: This article demonstrates the safety of reintroducing platelet-inhibitory doses of aspirin in patients in whom it is indicated and reporting aspirin-induced urticaria and/or angioedema with anti-inflammatory doses. However, patients with a history of chronic urticaria should undergo a challenge with the lowest platelet-inhibitory dose (75mg/day) in order to minimize the risk of aggravating their condition.

Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy.

BACKGROUND: To confirm allergy to beta-lactam (BL), a basophil activation test in flow cytometry based on CD63 up-regulation was described. CD203c is a more recent basophil activation marker and up to day there is no consensus about which marker is the more sensitive one. CD203c has not yet been evaluated in the diagnosis of BL allergy. OBJECTIVE: The aim of the study was to compare the reliability of CD203c to CD63 for the diagnosis of amoxicillin (AX) allergy, which is nowadays the most frequent BL allergy. METHODS: Twenty-seven patients with an immediate positive skin test (ST) to AX, 20 had had anaphylaxis with AX and 7 had urticaria and/or angioedema, were compared with 14 controls with no allergy to BL and to six patients with delayed positive ST to AX. RESULTS: In the anaphylaxis group, AX induced up-regulation of CD203c in the basophils of 12 patients out of 20 (60%) and of CD63 in four patients (20%) (P<0.02). Two patients out of seven with urticaria or angioedema had a positive result with CD203c and CD63. In patients who had anaphylaxis, ampicillin (AMP) induced CD203c up-regulation in eight out of 12 (67%) patients tested, and CD63 up-regulation in 4 out of 12 (33%) (all patients who had anaphylaxis could not be tested with AMP). False-positive results were observed with CD203c as well as CD63, and for 10 patients indeed this was confirmed by a negative drug provocation test. The origin of conflicting results between CD63 and CD203c might be at least the targeting of basophils based on anti-IgE labelling. Among IgE(+) gated cells, by means of CD33, a marker of monocytes, a contamination up to 50% by monocytes was detected. In contrast to CD63, CD203c is an activation marker specific of basophils with a basal low-level expression in resting basophils. Thus, IgE and CD203c double targeting of basophils avoids the contamination by monocytes. CONCLUSION: CD203c seems to be a more sensitive activation marker of basophils than CD63 for the diagnosis of amoxicillin allergy.

Head and neck atopic dermatitis and malassezia-furfur-specific IgE antibodies.

BACKGROUND: Atopic dermatitis of the head and neck (HNAD) has been recognized as a separate entity. Malassezia furfur, a lipophilic yeast, is considered to be a pathogenic allergen in this form of atopic dermatitis. OBJECTIVE: The purpose of this study was to determine the level of IgE anti-M.-furfur antibodies and their relation to the severity of the disease. METHODS: IgE anti-M.-furfur antibodies were assayed in 106 patients with HNAD. Controls included 25 patients with non-HNAD, 20 with nonatopic dermatitis and 16 with seborrheic dermatitis (including 4 with AIDS). RESULTS: There was a highly significant correlation between the level of anti-M.-furfur IgE and clinical severity. Furthermore, there was a significant but smaller correlation between total IgE and clinical severity. In patients with HNAD, total IgE was higher amongst men. CONCLUSION: IgE anti-M.-furfur antibodies are a good and specific marker for HNAD. IgE M. furfur levels are strongly correlated with the severity of the disease.

Prevention of latex sensitization in guinea pigs by a bacterial and viral filter used in anaesthesia.

BACKGROUND: Preventing anaphylactic reactions as a result of natural rubber latex (NRL) proteins is an important concern in anaesthesia. The clinical relevance of a bacterial/viral filter (Pall BB25) in preventing sensitization to NRL by inhalation was tested in guinea pigs. METHODS: Guinea pigs (n=8-10 in each group) were exposed to aerosolized NRL-contaminated cornstarch powder or to NRL in saline for 1 h every day for 2 weeks. The experiments were repeated with a Pall BB25 filter placed over the aerosol system. Control groups were exposed to non-contaminated cornstarch or to saline alone. Three weeks after the last exposure, specific bronchial challenge was performed and thromboxane (Tx) B2 levels in bronchoalveolar lavage fluid were measured. RESULTS: After bronchial challenge, the animals exposed to NRL or NRL-contaminated cornstarch with the BB25 filter in place showed a level of bronchoconstriction (i.e. the variation of pulmonary insufflation pressure) not different from controls. Conversely, those exposed to NRL or NRL-contaminated cornstarch without the filter showed a higher level of bronchoconstriction (respectively, P<0.02 and P<0.001) than control. Elevated TxB2 levels were found in the lungs of the guinea pigs, which inhaled NRL or NRL-contaminated cornstarch in the absence of a filter. Animals treated with the filter showed comparable TxB2 levels with those of control. CONCLUSION: The Pall BB25 filter efficiently protected the guinea pigs from sensitization to NRL. This filter can be used as a complementary measure for avoidance of NRL contact during surgical procedures particularly if the mechanical ventilator apparatus contain NRL devices.

Inhaled cornstarch glove powder increases latex-induced airway hyper-sensitivity in guinea-pigs.

BACKGROUND: Breathing is one of the most important modes of sensitization to natural rubber latex (NRL) for health-care workers, a group most at risk. Cornstarch powder (CSp) from medical powdered NRL gloves is known to be an allergen carrier, and sensitization to NRL can occur by inhaling airborne particles from such gloves. OBJECTIVE: The aim of this study was to demonstrate, using an experimental model, which CSp may act as an adjuvant in NRL-induced airway hyper-responsiveness. METHODS: Guinea-pigs were exposed to aerosolized NRL-contaminated CSp or to NRL in saline solution for 1 h every day for 2 weeks. The control groups were exposed either to CSp or to saline alone. An additional group of guinea-pigs was exposed to aerosolized ovalbumin (OVA) in saline. Three weeks after the last exposure, specific bronchial challenges were performed. In addition, Specific IgG and IgG1 in sera and thromboxane (Tx) B(2) levels in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: The NRL challenge caused significant bronchospasm in the animals that had been exposed to NRL compared with those in the control groups (P<0.02). Guinea-pigs exposed to OVA also demonstrated a significant bronchospasm after OVA challenge (P<0.001). The guinea-pigs that had inhaled NRL-contaminated CSp had a significantly higher bronchoconstriction level than those that had inhaled NRL alone (P<0.02). Specific IgG and IgG1 were undetectable in sera from all groups, whereas significant amounts of TxB(2) (P<0.001) were found in the lungs of the guinea-pigs exposed to NRL or OVA. CONCLUSION: Inhaling CSp increases the airway response to NRL. The fact that specific IgG and IgG1 were not detected might be the result of an immune response limited to the airways. This finding is supported by a significant increase of TxB(2) level in the BALF of sensitized guinea-pigs.

Immunoadjuvant properties of glove cornstarch powder in latex-induced hypersensitivity.

BACKGROUND: Cornstarch powder present in medical gloves plays an important role in latex-induced hypersensitivity as allergen carrier either, by the inhalation route, by skin contact or by direct contact with mucous membranes. OBJECTIVE: Our objective was to test the hypothesis that cornstarch could act as an immunoadjuvant in immediate type-I latex-induced hypersensitivity. METHODS: Guinea-pigs were sensitized by intraperitoneal route with two different antigens (latex proteins and ovalbumin) with or without cornstarch powder. Airway responsiveness after specific bronchial provocation was evaluated and specific IgG and IgG1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Controls were treated with cornstarch powder or saline alone. RESULTS: Animals sensitized with latex proteins (n = 7 in each group) showed significant bronchoconstriction (P < 0.03) and higher anti-latex antibody levels than the controls (P < 0.005). Guinea-pigs sensitized with latex-contaminated cornstarch had higher levels of specific antibodies than those sensitized with latex alone (P < 0.05). Animals sensitized to latex mixed with cornstarch showed higher bronchospasm than those treated with latex alone (P < 0.003). Animals sensitized to ovalbumin mixed with cornstarch also showed higher antibody and bronchoconstriction levels (P < 0.05) than those immunized with ovalbumin alone but antibody titres were significantly lower than those of the animals treated with ovalbumin and Freund's complete adjuvant (P < 0.01; n = 5 in each group). CONCLUSION: Our findings show that cornstarch powder increases antigen-induced bronchoconstriction and antibody production. This role of immunoadjuvant is not antigen-specific. The cornstarch powder used as donning agent in latex gloves is an allergen carrier and it can enhance latex-induced hypersensitivity.

[Chronic urticaria, thyroiditis and autologous serum test]. / Urticaire chronique, thyroïdite auto-immune et test au sérum autologue.

INTRODUCTION: The autoimmune nature of certain forms of chronic urticaria remains debatable. Aim of the study. To find a correlation in terms of autoimmune pattern between chronic urticaria and thyroiditis using the autologous serum test and the search for anti-thyroid antibodies. PATIENTS AND METHODS: Study in a single center of 59 patients having consulted for urticaria that had progressed for more than six weeks and without precise etiology. An autologous serum test was conducted and anti-thyroid autoantibodies were searched for in the serum stored after the test. RESULTS: Out of 59 patients, 51 had an interpretable autologous serum test and 57 underwent research for anti-thyroid antibodies. Twelve patients out 57 (21 p.cent) exhibited one or more types of positive (n=10) or borderline (n=2) anti-thyroid antibodies, and eight out of 12 (66.6 p.cent) had a known thyroid disease before the onset of urticaria. The systematic blood test permitted the discovery of 4 cases of unknown anti-thyroid antibodies. The symptoms regressed in two of these patients without any specific treatment, one patient was treated with L thyroxin for hyperthyroidism without any improvement in the symptoms and one other patient had normal thyroid function. Among these 12 patients, 11 underwent autologous serum tests, but only 3 of them exhibited clearly positive results and one was doubtful. CONCLUSIONS: Within the limits of this study, we found a 21 p.cent rate of patients with chronic urticaria exhibiting one or more anti-thyroid antibodies. The positivity of the autologous serum test does not appear to be related with autoimmune thyroid disorders.

Safety of various dosage regimens during induction of sublingual immunotherapy. A preliminary study.

BACKGROUND: Sublingual immunotherapy (SLIT) has been demonstrated to be a viable alternative to injection immunotherapy. Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated. The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients. METHODS: Sixty-four patients (age range 5-46 years) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind, placebo-controlled trial of SLIT. Sixty-three patients were randomized to four groups and evaluated at the end of the study. One group received placebo (n = 16) and the other three groups (n = 47) received five grass pollen extracts according to three different induction regimens: regimen 1 starting with 3 IR tablets (n = 15), regimen 2 starting with 10 IR (n = 16) and regimen 3 starting with 30 IR (n = 16). The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients. Adverse events were recorded on diary cards. RESULTS: During induction phase, 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group (p < 0.05). The rate of adverse reactions was 33.3% (11.8-61.6) (95% CI) for regimen 1, 31.3% (11.0-58.7) for regimen 2, 43.8% (19.8-70.1) for regimen 3 and 12.5% (1.6-38.3) for placebo. Fifty-seven reactions were local reactions involving the oral region (54 SLIT, 3 placebo) and 13 were systemic reactions (all in the SLIT groups). 11/13 reactions were mild (gastrointestinal disorders, rhinoconjunctivitis), 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain. No urticaria, angioedema or life-threatening events were observed. CONCLUSIONS: These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT.

[Responsibility of food in exercise-induced anaphylaxis: 7 cases]. / Rôle des aliments dans l'anaphylaxie induite par l'effort: 7 observations.

INTRODUCTION: Exercise induced-anaphylaxis is a rare allergic disease. In most cases, the ingestion of a specific food within a maximum of 4 hours preceding physical activity is necessary to develop the anaphylactic reaction. CASE-REPORTS: We report 7 cases of food-dependant exercise induced-anaphylaxis. The responsible foods were wheat (2 cases), corn, barley, shrimp, apple, paprika and mustard. The discovery of the food allergen and its systematic eviction 4 hours before the beginning of a physical effort led to the disappearance of clinical symptoms in all cases. DISCUSSION: The role of food in exercise-induced-anaphylaxis is essential. The food in cause varies but our study confirms the predominant role of cereal food which is a less sensitizer in adults, except in a context of effort. The responsibility of this type of food consumed daily can explain partially the frequent delay before diagnosis of this allergic disease.

[Anisakis simplex and immediate hypersensitivity reactions]. / Anisakis simplex et réactions d'hypersensibilité immédiate.

BACKGROUND: Anisakis simplex is one of the nematode worms that parasitize sea mammals. When its larvae are accidentally ingested by humans, they can infect the host, resulting in anisakiasis manifested by digestive symptoms, or they may cause an allergic reaction, which in some cases may be severe. CASE REPORTS: We report three cases of acute urticaria associated with abdominal pain, and hypotension in two of them, starting two to six hours after ingestion of raw fish. The diagnosis of an allergic reaction caused by Anisakis simplex was based on the clinical histories and positive tests for anisakis-specific IgE. DISCUSSION: In patients with acute urticaria associated with abdominal symptoms, a history of ingestion of raw fish in the preceeding hours is evocative of gastro-allergic anisakiasis. In association with symptomatic treatment, gastrointestinal endoscopy allows the larvae to be visualized and removed, which may relieve the symptoms and provide a diagnosis before the results of skin testing and serological assay are known.

Treatment of severe seasonal rhinoconjunctivitis by a combination of azelastine nasal spray and eye drops: a double-blind, double-placebo study.

BACKGROUND: Evaluation of combined azelastine nasal spray and eye drops treatment in patients with severe rhinoconjunctivitis. METHODS: Phase III, multicenter, randomized, double-blind study of patients with a history of grass pollen allergy, confirmed by skin testing/specific IgE, total symptom scores > or =6 (ocular) or > or =8 (nasal). Intent-to-treat analysis. RESULTS: 99 patients (azelastine = 53, placebo = 46) enrolled homogeneously from May to September 1997 in 7 venues in France. The efficacy of azelastine was significantly higher compared to placebo (49% vs. 28%, p = 0.04), considering response as a decrease of the total sum of ocular and nasal scores by at least 50% and no use of cetirizine by day 7. The decrease of total ocular and nasal scores by at least 50% at day 7, with cetirizine rescue <3 tablets was higher, but not significantly, in azelastine patients (43% vs. 30%). Cetirizine rescue was more frequent, from day 0 to 7, in the placebo patients (4.9 +/- 5.0 vs. 2.7 +/- 4.1, p = 0.02). Global efficacy was rated higher for azelastine by investigators (26% vs. 10%, p = 0.05) and patients (28% vs. 7%, p = 0.01). Adverse events were burning sensation, "red eyes," nasal irritation, bitter taste. No serious adverse events were reported. Tolerance of azelastine was "very good/good"/"satisfactory" in the majority (62%/82% assessed by investigators, or 55%/79% by patients, respectively). CONCLUSIONS: Combining azelastine eye drops and nasal spray is a safe and effective treatment of severe seasonal rhinoconjunctivitis.

[Vibratory angioedema]. / Angio-oedème vibratoire.

BACKGROUND: Vibratory angioedema is a rare form of physical urticaria. This entity can be an hereditary autosomal dominant disorder or an acquired sporadic disease. Immediate and delayed forms have been reported. CASE-REPORT: A 34-year-old woman was referred to us for a vibratory angioedema induced by mountain biking. Despite her handicap, she could provoke a clinical tolerance with disappearance of pruritus but not of erythema and edema if she continued her physical effort. Diagnosis was confirmed with a vibratory stimulus using a Vortex for 5 minutes. The realization of a controlled vibratory stimuli among 20 volunteers induced a positive response in 7 cases (35 p. 100). DISCUSSION: These results raise the problem of the specificity of the test but also point out the possible physiological response of the body to intense vibratory stimulations.

Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study.

BACKGROUND: Calcium phosphate-adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants. OBJECTIVES: A double-blind, placebo-controlled study was performed in order to confirm the safety and assess the efficacy of a standardized five-grass-pollen extract adsorbed onto calcium phosphate for specific immunotherapy (IT). METHODS: Twenty-nine patients with seasonal rhinoconjunctivitis were randomized to receive either the active preparation (16 patients) or placebo (13 patients), in a 1-year study. During the increasing dose phase, an extract ranging from 0.1 IR per ml to 50 IR per ml was administered at a rate of one subcutaneous injection per week until a maintenance dose was reached. The patients were assessed by symptom diary and rescue medications during seasonal exposure and specific nasal and skin reactivity before and after IT. Immunological parameters (specific IgE and IgG4 antibodies) were assessed before, during and after IT. RESULTS: The overall symptoms score (mean AUC) was not significantly different between the IT group and the placebo group during grass-pollen exposure (49.6 vs. 56, respectively). The total medication score (mean AUC) was significantly lower in the IT group than in the placebo group (11 vs. 41, P < 0.01, Mann-Whitney U-test). The cumulative symptom/medication score was significantly lower in the IT group than in the placebo group (64.5 vs. 102.3, P < 0.05, U-test). A significant increase in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL before IT vs. 63.4 IR/mL after IT, P < 0.01, Wilcoxon), whereas no significant changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL after IT). IT induced a significant reduction in grass pollen cutaneous reactivity in the actively treated group (P < 0.001). A significant increase in serum-specific IgG4 antibody response was observed in the IT group (3.1% before IT vs. 10.1% after IT, P < 0.001). Nine patients in the IT group developed moderate immediate systemic reactions vs. two patients in the placebo group. CONCLUSION: Specific immunotherapy with calcium phosphate-adsorbed standardized grass pollen extract was safe and effective for the treatment of patients with seasonal allergic rhinoconjunctivitis.