Epidemiological Data on Anaphylaxis in French Emergency Departments.

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxisrelated codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions.

Chronic anterior shoulder instability with significant Hill-Sachs lesion: Arthroscopic Bankart with remplissage versus open Latarjet procedure.

BACKGROUND: The objective of this study was to compare short-term shoulder stability after arthroscopic Bankart repair with remplissage versus the open Latarjet procedure in patients who had chronic anterior shoulder instability with a significant Hill-Sachs lesion. HYPOTHESIS: The dislocation recurrence rate is higher after Bankart repair with remplissage than after open Latarjet. PATIENTS AND METHODS: An observational non-randomised retrospective cohort study was conducted at two surgical centres in patients treated for chronic anterior shoulder instability with a significant Hill-Sachs defect between January 2009 and July 2014. The study compared 43 patients managed by arthroscopic Bankart repair and remplissage and 43 patients managed with open Latarjet. The two groups were matched on age at surgery and on follow-up duration. All patients were evaluated by independent observers based on a questionnaire including recurrences, range of motion, and functional outcomes (Shoulder Subjective Value [SSV], Walch-Duplay score, and Rowe score). RESULTS: Mean follow-up was 47.3 months (range, 24-67 months). The recurrence rate at last follow-up was not significantly different between the two groups (9.3% versus 11.2%; P=0.67). The Bankart group had significantly greater loss of external rotation and a significantly higher proportion of patients with residual pain (21% versus 9%, P=0.023). The SSV, Walch-Duplay score, and Rowe score values were similar between groups. DISCUSSION: In patients who had chronic anterior shoulder instability with a significant Hill-Sachs lesion, arthroscopic Bankart repair with remplissage and open Latarjet were reliable and safe procedures associated with low and similar recurrence rates. However, loss of external rotation and residual pain were significantly more common with the combined Bankart-remplissage procedure. LEVEL OF EVIDENCE: III; comparative retrospective study.

Severe anaphylaxis to Propofol: first case of evidence of sensitization to soy oil.

The growing worldwide prevalence of food allergies is drawing attention to the risk of allergenic proteins found in intravenous medicinal products, particularly anaesthetics. Propofol induced anaphylaxis has been described. The presence of soybean oil and egg lecithins in the lipid emulsion highlights their suspected responsibility in certain cases. We report a case of anaphylaxis to propofol in an adult patient without food allergy to soy, but with a latent sensitization to soy. An IgE-dependent allergy to propofol was established by a basophil activation test. Here, we document for the first time the existence of specific IgEs to a 65kDa protein, found in soybean oil and soy flour. In the absence of data on the reactogenic threshold for allergenic food proteins injected intravenously, a risk appears to be established and leads us to recommend a systematic detection for proteins in the refined soybean oil used in the pharmaceutical industry for intravenous products.

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.

Is coracoclavicular stabilisation alone sufficient for the endoscopic treatment of severe acromioclavicular joint dislocation (Rockwood types III, IV, and V)?

BACKGROUND: The primary objective was to evaluate correlations linking anatomical to functional outcomes after endoscopically assisted repair of acute acromioclavicular joint dislocation (ACJD). HYPOTHESIS: Combined acromioclavicular and coracoclavicular stabilisation improves radiological outcomes compared to coracoclavicular stabilisation alone. MATERIAL AND METHODS: A prospective multicentre study was performed. Clinical outcome measures were pain intensity on a visual analogue scale (VAS), subjective functional impairment (QuickDASH score), and Constant's score. Anatomical outcomes were assessed on standard radiographs (anteroposterior view of the acromioclavicular girdle and bilateral axillary views) obtained preoperatively and postoperatively and on postoperative dynamic radiographs taken as described by Tauber et al. RESULTS: Of 116 patients with acute ACJD included in the study, 48% had type III, 30% type IV, and 22% type V ACJD according to the Rockwood classification. Coracoclavicular stabilisation was achieved using a double endobutton in 93% of patients, and concomitant acromioclavicular stabilisation was performed in 50% of patients. The objective functional outcome was good, with an unweighted Constant's score ≥ 85/100 and a subjective QuickDASH functional disability score ≤ 10 in 75% of patients. The radiographic analysis showed significant improvements from the preoperative to the 1-year postoperative values in the vertical plane (decrease in the coracoclavicular ratio from 214 to 128%, p=10(-6)) and in the horizontal plane (decrease in posterior displacement from 4 to 0mm, p=5×10(-5)). The anatomical outcome correlated significantly with the functional outcome (absolute R value=0.19 and p=0.045). We found no statistically significant differences across the various types of constructs used. Intra-operative control of the acromioclavicular joint did not improve the result. Implantation of a biological graft significantly improved both the anatomical outcome in the vertical plane (p=0.04) and acromioclavicular stabilisation in the horizontal plane (p=0.02). The coracoclavicular ratio on the anteroposterior radiograph was adversely affected by a longer time from injury to surgery (p=0.02) and by a higher body mass index (BMI) (p=0.006). High BMI also had a negative effect on the difference in the distance separating the anterior edge of the acromion from the anterior edge of the clavicle between the injured and uninjured sides, as assessed on the axillary views (p=0.009). CONCLUSION: This study demonstrates that acute ACJD requires stabilisation in both planes, i.e., at the coracoclavicular junction and at the acromioclavicular joint. Coracoclavicular stabilisation alone is not sufficient, regardless of the type of implant used. Implantation of a biological graft should be considered when the time from injury to surgery is longer than 10days. The weight of the upper limb should be taken into account, with 6weeks of immobilisation to unload the construct in patients who have high BMI values. LEVEL OF EVIDENCE: II, prospective non-randomised comparative study.

Prognostic factors to succeed in surgical treatment of chronic acromioclavicular dislocations.

INTRODUCTION: Treatment of chronic acromioclavicular joint dislocation (ACJD) remains a poorly known and controversial subject. Given the many surgical options, it is not always easy to determine which steps are indispensable. METHODS: This article reports a multicenter prospective study. The clinical and radiological follow-up involved a comparative analysis of the preoperative and postoperative data at 1 year, including pain (visual analogue scale), subjective functional incapacity (QuickDASH), and the objective Constant score, as well as a comparative analysis of vertical and horizontal movements measured on simple x-rays. RESULTS: Based on a series of 140 operated ACJDs, we included 24 chronic ACJDs. The mean time to surgery was 46 weeks (range, 1 month to 4 years). The patients' mean age was 41 years, with a majority of males (75%), 72% of whom participated in recreational sports. Professionally, 40% of the subjects had jobs involving manual labor. We noted 40% grade III, 24% grade IV, and 36% grade V injury according to the Rockwood classification. In 92% of cases, coracoclavicular stabilization was provided by a double button implant, reinforced with a biological graft in 88% of the cases. In 29%, millimeters to centimeters of the distal clavicle were resected and acromioclavicular stabilization was associated in 54%. We observed complications in 33% of the cases. At 1 year postoperative, 21 patients underwent clinical and radiological follow-up (87.5%). Only 35% of the patients were satisfied or very satisfied, whereas 100% of them would recommend the operation. Full-time work was resumed in 91% of the cases and all sports could be resumed in 86%. The pre- and postoperative values at 1 year changed as follows: the mean Constant score improved from 61 to 87 (p=0.00002); the subjective QuickDASH score decreased from 41 to 9 (p=0.00002); and radiologically significant reduction of the initial displacement was observed in the vertical plane (p<10(-3)) and the horizontal plane (p=0.022). CONCLUSION: In this study, the favorable prognostic factors found were: time to surgery less than 3 months (p=0.02), associated acromioclavicular stabilization, and postoperative immobilization with a sling extended to 6 weeks. However, resection of the distal clavicle did not influence the final result. LEVEL OF PROOF: Level II prospective non-randomized comparative study.

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.

Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3 enzymes catabolizing bradykinin.

New concepts of idiopathic and iatrogenic angioedema underline the role of bradykinin, and the importance of catabolizing enzymes. A case is described of Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced angioedema, where AO attacks decreased after the withdrawal of lisinopril but resolved only after the withdrawal of sitagliptin, an inhibitor of dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased down to 17%, 42%, 64% of median references values, and remained low one year after the interruption of these drugs: 56%, 28% and 50%, respectively. The combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP IV inhibitor. The fact that this triple deficiency remained latent before and after the treatment indicates that searching for latent enzyme deficiencies should be carried out when there is intention to treat with a combination of drugs interfering with the bradykinin metabolism.

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.

Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.

BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney.

Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy.

BACKGROUND: Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms. However, the natural history is left unchanged. OBJECTIVE: To search for a beneficial effect of an oral desensitization protocol to allergenic foods in IgE-dependent milk or egg allergies in children. METHODS: 60 children with documented cow's milk allergy (13 months-6.5 years), and 90 children with egg allergy (12 months-8 years), were consecutively included after 6-12 months of avoidance diet, if a SBPCFC to 60 ml milk (60 ml) or to 965 mg of raw egg white was negative. They were randomized for uninterrupted avoidance or oral desensitization (group A or OD). Six months later, a new SBPCFC was performed with, up to 200 ml of milk or 7g of raw egg white. Prick tests and specific IgE levels were carried out simultaneously. RESULTS: Data were obtained for 57 children with CMA (30 A and 27 OD), and 84 children with EA (35 A and 49 OD). The two groups (AD or OD group) were similar with regard to means of ages, the size of PT wheals and the level of IgEs at baseline. MILK ALLERGY: A SBPCFC to milk was positive in 11.1% of those following OD vs. 40% after A (p < .025). The size of PT decreased after OD and increased after A (-3.4 mm vs. +0.84 mm; p < .002). EGG ALLERGY: The SBPCFC to egg was positive in 30.6% after OD vs. 48.6% after A (p < .1). After 6 months, in the OD group, the mean size of the PT and the level of specific IgE were significantly reduced compared to the A group. In the A group, the threshold of reactivity was often lower, or more serious symptoms were observed. CONCLUSION: Oral desensitization helps the egg and milk allergic children to overcome their allergies. Since the avoidance of these foods is likely to increase sensitization as well as to lower the threshold of reactivity, an active treatment is required. Further attempts to standardize the procedures of oral desensitization are expected.

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.

Epidemiology of life-threatening and lethal anaphylaxis: a review.

Severe anaphylaxis is a systemic reaction affecting two or more organs or systems and is due to the release of active mediators from mast cells and basophils. A four-grade classification routinely places 'severe' anaphylaxis in grades 3 and 4 (death could be graded as grade 5). Studies are underway to determine the prevalence of severe and lethal anaphylaxis in different populations and the relative frequencies of food, drug, latex and Hymenoptera anaphylaxis. These studies will also analyse the risk arising from the lack of preventive measures applied in schools (personalized management protocols) and from the insufficient use of self-injected adrenalin. Allergy-related conditions may account for 0.2-1% of emergency consultations. Severe anaphylaxis affects 1-3 per 10 000 people, but for the United States and Australia figures are even higher. It is estimated to cause death in 0.65-2% of patients, i.e. 1-3 per million people. An increased prevalence has been revealed by monitoring hospitalized populations by reference to the international classification of disease (ICD) codes. The relative frequency of aetiological factors of allergy (food, drugs, insects and latex) varies in different studies. Food, drug and Hymenoptera allergies are potentially lethal. The risk of food-mediated anaphylaxis can be assessed from the number of personalized management protocols in French schools: 0.065%. Another means of assessment may be the rate of adrenalin prescriptions. However, an overestimation of the anaphylaxis risk may result from this method (0.95% of Canadian children). Data from the literature leads to several possibilities. First, a definition of severe anaphylaxis should be agreed. Secondly, prospective, multicentre enquiries, using ICD codes, should be implemented. Moreover, the high number of anaphylaxis cases for which the aetiology is not identified, and the variation in aetiology in the published series, indicate that a closer cooperation between emergency specialists and allergists is essential.

Allergy to nickel in dental alloys.

A case of oral allergy to dental alloys is presented, highlighting the interest of dosage of salivary nickel and of flow cytometry showing a selective CD4+ activation. The discrepancy between the rarity of oral allergy to dental alloys and the frequency of nickel sensitization and nickel-induced contact dermatitis leads to discuss the mechanisms of oral tolerance.

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.

Severe food anaphylaxis: 107 cases registered in 2002 by the Allergy Vigilance Network.

BACKGROUND: The prevalence of food allergies increases, relating to diet modifications. The consumption of new foods--exotic foods or foods originally used for animal feed, new proteins, neo allergens due to the use of new technologies and soon, Genetically Modified Foods--are in the spotlight. OBJECTIVE: It is essential to develop a system of food allergy vigilance encompassing the full range of foods being consumed. Understanding this imperative leads logically to the suggestion of developing an allergy vigilance network taking advantage of the ongoing experience of allergists "on the ground". METHODS: The French Allergy Vigilance Network is subscribed to by 302 allergologists (267 of whom are French). The aims of the Network are to record cases of severe anaphylaxis, to establish an epidemiological data bank from prospective multicenter studies, and to monitor the allergic risk from novel foods. RESULTS: In 2002, 107 cases of severe anaphylaxis were recorded: anaphylactic shock--59.8% (one fatal), systemic reaction--18.7%, laryngeal angio-edema--15.9%, acute severe asthma--5.6% (one fatal). The main allergens identified were peanuts, nuts, shellfish, lupine flour and wheat flour. Action has been taken as a result: information by industry on inadequate labeling, withdrawal of wrongly labeled batches, and university hospital centers have been encouraged to establish the allergenic safety of their catering services. CONCLUSION: Setting up such a network in other countries would lead to a significant advance in knowledge of the peculiarities of allergies relating to a wide variety of eating habits.