Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life.

BACKGROUND: The MIRABEL survey is an observational study on peanut allergy in France, Belgium and Luxemburg. The objectives are to provide data on a large population, to analyse the consumer behaviour, to study the presence of peanut traces in pre-packed foods with/without precautionary allergen labelling (PAL), and to combine these data to quantify allergic risk and produce a cost/benefit analysis. This paper reports a real-life observatory of 785 patients (< 16y: 86%): medical characteristics, eliciting doses (ED) in real life and in oral food challenges (OFC), factors associated with severe reactions, allergist dietary advice and patients' anxiety regarding their allergy. METHODS: Age and symptoms at diagnosis, route of exposure, comorbidities, allergy tests, ED (OFC/real life; mg peanut protein), dietary advice about PAL, and anxiety score were recorded. RESULTS: Median age was 3 years; 85% were declared allergic. Severe/potentially severe reactions were reported in 30% of the allergic patients: serious systemic reaction (15%), laryngeal angioedema (8%), shock (4%) and acute asthma (3%); 66% had atopic dermatitis, 58% asthma. Median ara h 2 sIgE level was 11.5 kUA/L. Of the 278 OFCs, 225 were positive (median ED: 67.3 mg). Real-life ED was < 100 mg in 44.3%. Severe reactions were significantly more frequent in teenagers and adults (P = 0.004), asthmatic patients (P = 0.033), and patients who reacted to inhalation (P < 0.001). No significant association was found for OFC ED or ara h 2 sIgE. Factors associated with strict avoidance advice including PAL were OFC ED < 100 mg (P < 0.001), but not severe reaction history (P = 0.051) or asthma (P = 0.34). Anxiety was significantly associated with strict avoidance (P < 0.001). CONCLUSION AND CLINICAL RELEVANCE: Severe/potentially severe reactions, allergic comorbidities, and low EDs in real life are frequent in peanut-allergic patients. Asthma, teenage/adulthood and reaction to inhalation are associated with severe symptoms. PAL and criteria guiding dietary advice need to be improved.

Anaphylaxis to diclofenac: nine cases reported to the Allergy Vigilance Network in France.

Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance Network in France from 2002 to 2012 were studied. Data from history, symptoms, skin tests, basophil activation tests, and oral challenge (OC) were recorded. Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE-dependent anaphylaxis was confirmed in six cases: positive intradermal tests (n = 4), a syndromic reaction during skin tests (n = 1), and one case with grade 1 reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune reaction was suspected in one case. An IgE-dependent mechanism may be the predominant cause of adverse reactions to diclofenac. Allergy skin tests must be carried out sequentially at the recommended concentrations. BATs may be helpful because they can support the diagnosis of anaphylaxis. Given the risks of a direct challenge to diclofenac, OC to aspirin should be performed first to exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed.

Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010.

BACKGROUND: A few series of well-documented cases of severe drug-induced anaphylaxis (SDA) are available. METHODS: Cases collected by the Allergy Vigilance Network from 2002 to 2010 were analyzed for clinical signs, causative drugs, and efficacy of a stepwise approach to diagnosis, using skin tests, laboratory tests, and oral challenges. RESULTS: Three hundred and thirty-three cases concerned 300 adults (90.1%) and 33 children (9.9%): 206 females (61.9%) and 127 males (38.1%). Mean age was 42.7 ± 18 years. Anaphylactic shock (76.6%), severe systemic reactions (10.5%), acute laryngeal edema (9%), severe bronchospasm (2.1%), and six fatal cases (1.8%) were recorded. There were 270 cases (81.1%) of ambulatory anaphylaxis. Sixty-three cases (18.9%) occurred during anesthesia. Hospitalization was required in 94.8% of cases. 23.7% of patients were admitted to an intensive care unit. Epinephrine was used in 57.9% of cases. Eighty-four drugs were incriminated: antibiotics (49.6%), muscle relaxants, latex and anesthetics (15%), nonsteroidal anti-inflammatory drugs (10.2%), acetaminophen (3.9%), iodinated or magnetic resonance imaging contrast media (4.2%), immunotherapy and vaccines (3.9%), and other drugs (13%). Among antibiotics, amoxicillin (97 cases), other penicillins (four cases), cephalosporins (41 cases), quinolones (15 cases), and pristinamycin (seven cases) were the most common. The diagnosis of drug hypersensitivity was obtained by skin tests in 72.9%, laboratory tests only in 2.4% of cases, and oral challenges (OCs) only in 3.9% of cases. CONCLUSIONS: Three hundred and thirty-three case reports provided data on drugs involved in severe anaphylaxis. The efficacy of skin tests and poor use of laboratory tests are underlined. Further progress may depend on OCs.

Acute deep vein thrombosis and endovascular techniques: It is time for a new aggiornamento!

The stated aims of treating acute deep vein thrombosis (DVT) are to prevent a pulmonary embolism, stop the clot from spreading, reduce the risk of a recurrence; they are less concerned with the late morbidity associated with post-thrombotic syndrome (PTS). In accordance with the French (Afssaps, 2009) and North American (ACCP, 2008) recommendations, anticoagulants (LMWH, heparin, AVK) form the cornerstone for treating DVT. These treatments appear to be far less effective in preventing post-thrombotic syndrome (PTS), associated with venous hypertension, residual occlusion, and with reflux caused by valve incompetence. Given that, the new aim is to optimise the prevention of PTS, the ACCP guidelines, unlike those of Afssaps, "suggest" for selected patients suffering from acute iliofemoral DVT, the use of both classic anticoagulants, and in situ percutaneous administration of thrombolytic drugs (recommendation grade 2B) and simultaneous correction of any underlying anatomical anomalies using angioplasty and stenting (recommendation 2C). Contemporary endovascular methods, referred to collectively as "facilitated" thrombolysis, combine low doses of rtPa or Urokinase administered locally, and the removal of the clot using various mechanical, rotating, rheolytic systems, or using ultrasound. The results of non-randomised, heterogeneous studies objectivised a lysis rate of 80%, a 50% lower risk of haemorrhage complications compared with systemic thrombolysis (<4%), and a clear reduction in treatment time (one-shot methods possible for procedures lasting less than 2 hours). This data ties in with the modern "open vein" concept which underpins the hope of an improvement in the late prognosis of acute DVT, through the removal of a clot, thereby improving permeability and valve integrity; this hypothesis is supported by the results at 24 months of a randomised CaVent objectifying absolute risk reduction of 15% in the thrombolysis in situ. The current randomised study (ATTRACT trial) comparing the combination of "facilitated thrombolysis" in addition to the usual treatment with the traditional treatment alone for acute iliofemoral DVT, the statistical power of which has been established (600 patients) to authenticate a reduction by a third in the number of PTS (CaVent trial, showing a 15% reduction rate of 24 months PTS in the thrombolysed group results expected in 2016), might, if the results are positive, lead to a profound change in the paradigms for the treatment of acute iliofemoral DVT.

A 38-year-old hairdresser with irritant-associated vocal cord dysfunction.

The present case study reports the first case of a 38-year-old hairdresser with irritant-associated vocal cord dysfunction (VCD) due to alkaline persulfate, who was referred on suspicion of occupational asthma. Several tests were performed, including specific inhalation challenge and upper airway endoscopy. During the specific inhalation challenge to alkaline persulfate, the patient experienced dysphonia and a non-significant decrease in forced expiratory volume in 1 second on spirometry. Upper airway endoscopy was then performed and revealed VCD. A specific inhalation challenge test is therefore essential in cases of VCD to exclude possible concomitant occupational asthma.

Prevalence of sensitisation to oilseed rape and maize pollens in France: a multi-center study carried out by the Allergo-Vigilance Network.

BACKGROUND: Oilseed rape and maize crops represent a large part of agriculture fields in European countries. OBJECTIVE: To establish the actual prevalence of sensitization to oilseed rape and maize pollen, and to determine if this is correlated to the amount of exposure as well as to the patient's history of atopy or asymptomatic atopy. METHODS: The study was conducted by 69 allergists belonging to the Allergo-Vigilance Network, in collaboration with the French Agency for Safety of food, and compiles the results of skin prick-tests using oilseed rape and maize pollens and seeds, as well as common aeroallergens. The patients were classified into 3 groups: nonatopic, asymptomatic atopy, and actual atopic diseases. RESULTS: Among the 5372 subjects studied (2515 children, 2857 adults), 62.3% had an atopic disease, 10.2% had an asymptomatic atopy, and 27.5% were non-atopic. The level of sensitization was higher in the subjects with atopic disease, as compared to those with asymptomatic atopy: oilseed rape pollen: 11.8% vs 8%, maize pollen, 26% vs 19%, oilseed rape seeds, 7.7% vs 6.9%, corn seeds: 8.3% vs 4.8% (p < 0.001). The rate of sensitization was significantly increased in those living in high crop density regions. The association of an atopic disease with a high rate of exposure yielded a higher rate of sensitization of 13.8% and 21.3% for rapeseed pollen, and 22.9% and 30.7% for maize pollen in both children and adults, respectively. CONCLUSIONS: The incidence of sensitisation to rapeseed and maize pollen is positively correlated to the level of exposure. This prevalence is higher in patients with actual atopic disease as compared to those with asymptomatic atopy. The frequency of sensitization confirms the allergenicity of these plants destined for food supply and demonstrates the importance of monitoring for respiratory allergies to these pollens, not only in workers exposed to these types of crops, but also in atopic patients living in regions that contain a high density of rapeseed and maize fields. Cross-reactivities between pollens and seeds could potentially elicit cross-reacting food allergies.

Correlation between improvement in functional signs and plethysmographic parameters during venoactive treatment (Cyclo 3 Fort).

AIM: The aim of this study was to compare the change in functional signs of venous insufficiency and venous refilling time measured by mercury strain-gauge plethysmography under the effects of the combination of Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid (Cyclo 3 Fort). METHODS: An open-label clinical trial conducted in 65 women presenting with CEAP class C2s and C3s assessment criteria. At D0 and D28, functional signs were measured on a visual analog scale (VAS), venous refilling time by mercury strain-gauge plethysmography and venous reflux by echo-Doppler method. RESULTS: Under treatment, venous refilling time increased from 11.7±4 s to 13.8±4.4 s with Δ of 26% (P<0.0001) and the percentage of patients showing improvement of functional symptoms ≥30% was significantly correlated (P=0.04) with the percentage of patients presenting an improvement in venous refilling time ≥10%. CONCLUSION: Improvement in subjective functional signs under treatment with Cyclo 3 Fort was correlated with objective plethysmographic parameter improvement. There-fore, this study contributes to objectively document the benefit of prescribing this venoactive drug to active women with CEAP class C2s to C3s.

A novel immunoassay using recombinant allergens simplifies peanut allergy diagnosis.

BACKGROUND: Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. METHODS: The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n=166); pollen-sensitized subjects without peanut allergy (n=61), and control subjects without allergic disease (n=10). RESULTS: Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). CONCLUSION: A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results.

2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group.

BACKGROUND: In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and Recommendations methodology. MATERIAL AND METHODS: A literature review (1990-2007) on CVC-associated thrombosis was carried out. The guidelines were developed on the basis of the corresponding levels of evidence derived from analysis of the 36 of 175 publications selected. They were then peer reviewed by 65 independent experts. RESULTS: For the prevention of CVC-associated thrombosis, the distal tip of the CVC should be placed at the junction between the superior cava vein and right atrium; anticoagulants are not recommended. Treatment of CVC-associated thrombosis should be based on the prolonged use of low-molecular weight heparins. Maintenance of the catheter is justified if it is mandatory, functional, in the right position, and not infected, with a favorable clinical evolution under close monitoring; anticoagulant treatment should then be continued as long as the catheter is present. CONCLUSIONS: Several rigorous studies do not support the use of anticoagulants for the prevention of CVC-associated thrombosis. Treatment of CVC-associated thrombosis relies on the same principles as those applied in the treatment of established thrombosis in cancer patients.

A murine model of cow's milk protein-induced allergic reaction: use for safety assessment of hidden milk allergens.

BACKGROUND: Masked allergens in processed food products can lead to severe allergic reactions following unintentional ingestion. We sought to develop a murine model for the detection of hidden cow's milk proteins (CMP). This study aimed to induce cow's milk allergy in mice, to characterize the anaphylaxis induced by CMP in this model, and to validate its reliability using three margarines manufactured with (A) or without (B, C) milk, sharing the same production line. MATERIALS AND METHODS: Three-week-old BALB/c mice were sensitized intragastrically with CMP plus cholera toxin and boosted 6 times at weekly intervals. CMP-sensitization status was monitored by skin tests, and measurement of CMP-specific IgE and IgG1 levels. On day 44, the minimal threshold of clinical reactivity to CMP in terms of anaphylaxis was determined by performing a dose response of intraperitoneal CMP challenge. Under the same conditions, anaphylaxis was evaluated in CMP-sensitized mice after challenge with protein extracts of margarines A, B or C. RESULTS: Sensitization to CMP was demonstrated by positive skin tests and increased CMP-specific IgE and IgG1. The minimal clinical reactivity threshold corresponding to 0.1 mg CMP elicited detectable anaphylaxis evidenced by clinical symptoms, a decrease in breathing frequency, and increased plasma histamine upon challenge. Similarly, challenges with margarine A containing CMP demonstrated anaphylaxis, whereas those with B or C did not elicit any detectable allergic reaction. CONCLUSION: This study shows that our murine model of CMP-induced anaphylaxis is useful for investigating the allergenic activity and the assessment of margarines with respect to milk.

Food-dependent exercise-induced anaphylaxis--update and current data.

Exercise-induced anaphylaxis (EIA) is defined as the onset of allergic symptoms during, or immediately after, exercise, the clinical signs being various degrees of urticaria, angioedema, respiratory and gastrointestinal signs and even anaphylactic shock. Food-dependent exercise-induced anaphylaxis (FDEIA) introduces food in the syndrome and is revealed by a chronological sequence in which food intake, followed by exercise, induces symptoms after a varying period. When the food intake and the exercise are independent of each other, there are no symptoms. FDEIA is not very frequent. Identifying the culprit food allergen depends on the patient's eating habits. Crustaceans and wheat flour are the two commonest but others foods can be implicated. The patho-physiology of FDEIA has not been clearly established but it appears to result from degranulation of mast cells. As with food allergy, FDEIA diagnosis is based on interview, skin and biological tests and challenge. For the clinical signs of allergy, antihistamines, corticosteroids and epinephrine may be administered. Prophylaxis aims to prevent a recurrence; the patient should be given an emergency kit to deal with any recurrent episode. After the food allergen has been identified, it should be avoided for at least 4 to 5 hours before any exercise.

Immediate hypersensitivity to chlorhexidine: literature review.

Chlorhexidine, an antiseptic belonging to family of biguanides, is used extensively in the medical and surgical environment. Late onset hypersensitivity and eczema occur regularly and are well documented events. Conversely, immediate hypersensitivity, sometimes taking the form of acute urticaria that can result in anaphylactic shock, is rarer. These manifestations can occur during contact of the skin or mucosa with chlorhexidine. Out of the fifty case reports of chlorhexidine-related anaphylaxis published worldwide over the past ten years, fifteen occurred during surgery. Signs generally appear from 15 to 45 minutes after the start of anesthesia. If there is any suspicion of immediate allergy to chlorhexidine, prick-tests or even intradermal reaction (IDR) techniques are highly recommended. In the event of confirmed allergy to chlorhexidine, strict eviction is required, bearing in mind that over a hundred medicinal products currently on the French market contain chlorhexidine.

Anaphylactic shock induced by gadoterate meglumine (DOTAREM).

The use of contrast agent for magnetic resonance imaging improves the effectiveness of this diagnostic examination. Complexes of godolinium, which appear to be well tolerated, are used for this purpose. A few cases of anaphylactic shock have been attributed to these agents. We report a case of anaphylactic shock due to gadoterate meglumine (DOTAREM). While undergoing a magnetic resonance imaging examination, a 33-year-old nonatopic female patient became severely hypotensive, lost consciousness, and had generalized erythema immediately after the intravenous injection of this product. She recovered rapidly after she was given injection of epinephrine and her blood volume was restored with intravenous fluids. That DOTAREM had caused this immediate hypersensitivity reaction was proven by the positivity of prick-test and intradermal test at 10-3 (0.37 mg/ml) and in vitro leukocyte histamine release test. The results of these tests indicated that it was the gadoteric acid rather than the meglumine component of DOTAREM that was responsible: positivity of IDR at 10 mg/ml. Skin tests and leukocyte histamine release test to gadopentetate dimeglumine (MAGNEVIST) were negative. In addition of the exceptional character, this observation provides evidence for an immediate hypersensitivity without cross reactivity with gadopentetate dimeglumine.

[Allergies in orthodontics]. / Les allergies en orthodontie.

In contrast with work-related allergies amongst dentists and dental prosthetictists, allergies in patients followed in orthodontics concerning the materials placed in the mouth were rare. It may be a question of limited manifestations in the buccal cavity (urticaria, angio-oedema, stomatitis, chellitis), or more generalised manifestations (Quincke's oedema, eczema). The number of materials used in orthodontics is limited. The observations concerning metals are less numerous whilst those that concern the resins are exceptional. On the other hand, the risk linked to latex is very real. Allergy investigations require skin tests, sometimes to mucous tests and in some cases to provocation tests. Use of eviction measures may be not only the only diagnostic method but also a therapeutic method. Systematic search for an allergy to metal or a resin posed by the prosthetic material does not seem to be necessary. In the case of suspicion of latex, confirmed ultimately by an allergic history, this imposes start of the eviction measures.

[Anaphylactoid reactions and late skin reactions to iodinated contrast media: present state of the question--idea development]. / Réactions anaphylactoïdes et cutanées tardives aux produits de contraste iodés: état actuel de la question--évolution des idées.

PURPOSE: Adverse reactions to iodinated contrast media (ICM) share various mechanisms. Anaphylactoid reactions are among the most serious reactions when they are characterized by the elevation of seric tryptase. Pretreatment with corticosteroids and anti-H1 or the use of non-ionic contrast media do not prevent anaphylaxis. Late skin reactions could be mostly related to delayed hypersensitivity. Previous reactions to contrast media, cardiovascular disorders, beta-blockers, asthma, and atopy are risk factors. Female gender and age increase the severity. CURRENT KNOWLEDGE AND KEY POINTS: Anaphylaxis can be demonstrated by intradermal tests and the identification of specific IgEs. Delayed hypersensitivity is shown by the results of epicutaneous tests and the immunohistology of the skin. FUTURE PROSPECTS AND PROJECTS: Allergologic tests are advised in the case of previous reactions. In case of emergency, gadopentetate dimeglumine can be alternatively used. The other risk factors lead to the combination of pretreatment and use of non-ionic monomeric contrast media. Immediate hypersensitivity to iodinated media might increase in the near future with the use of divalent molecules.