An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.

Comparative epidemiology of suspected perioperative hypersensitivity reactions.

Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.

Chlorhexidine-induced anaphylaxis occurring in the workplace in a health-care worker: case report and review of the literature.

BACKGROUND: Chlorhexidine has been widely used in the occupational field as an effective antiseptic and disinfectant, especially in the health-care services. Several cases of allergic reactions to chlorhexidine have been reported, both in the general population and in workers. OBJECTIVES: To describe a case of occupational chlorhexidine-induced severe anaphylaxis that occurred in the workplace in a health-care worker (HCW) and to update the literature on chlorhexidine as a possible occupational allergen. METHODS: We report a case of a severe anaphylactic reaction that occurred in the workplace in a 63-year-old man, who had worked as a dentist for over 20 years. We also carried out a systematic review of the literature according to the PRISMA guidelines. No time or language filters were applied. Only occupational case-reports and case-series were included. RESULTS: The causative role of chlorhexidine was suspected owing to the presence of chlorhexidine-containing products in the workplace. Positive results on the Basophil Activation Test confirmed the diagnosis of immediate chlorhexidine-induced hypersensitivity reaction and excluded a role of other disinfectants. No other causes of anaphylaxis were suspected. Our systematic literature review identified 14 cases of occupational chlorhexidine-induced allergy among HCWs; in these cases, the clinical presentation was mild and the symptoms resolved. No cases of systemic reactions in the workplace were reported. CONCLUSIONS: This is the first report of chlorhexidine-induced severe anaphylaxis occurring in the workplace. This case report underlines the importance of investigating and being aware of individual and environmental risk factors in the occupational field, which can cause, albeit infrequently, severe reactions with serious consequences.

Birch allergy and oral allergy syndrome: The practical relevance of serum immunoglobulin E to Bet v 1.

BACKGROUND: Birch allergy (BA) may frequently be associated with fruit-vegetables oral allergy syndrome (OAS). Bet v 1 is the major birch allergen. Previously, it was reported that serum-specific immunoglobulin E (IgE) level could differentiate allergy from sensitization. Thus, this study aimed to investigate the practical role of Bet v 1 IgE. METHODS: A total of 245 subjects (128 women, 117 men; mean age, 41 years) with suspected allergic rhinitis and sensitization to Bet v 1 were evaluated. Serum IgE to Bet v 1 was assessed by using immuno-enzymatic. BA and OAS were diagnosed according to validated criteria. Symptom severity perception was measured by the visual analog scale. RESULTS: A total of 158 patients (64.5%) had BA. Patients with BA had higher serum Bet v 1 IgE levels than subjects who were sensitized (p < 0.0001). A cutoff value of 8.94 kUA/L predicted BA (area under the curve, 0.76; odds ratio, 6.18). Fifty-three patients with BA (33.5%) had OAS. Patients positive for OAS had higher Bet v 1 levels (p < 0.0001) and more-severe symptoms (p < 0.0001) than patients with BA and negative for OAS. A cutoff value of 17.4 kUA/L predicted OAS (area under the curve, 0.59; odds ratio, 3.19). CONCLUSIONS: The present study demonstrated that serum IgE levels to Bet v 1 could be a useful marker for differentiating between different birch pollen sensitization phenotypes.

Hymenoptera venom allergy in outdoor workers: Occupational exposure, clinical features and effects of allergen immunotherapy.

OBJECTIVES: To describe (i) the clinical characteristics of workers, exposed to hymenoptera stings, with an ascertained diagnosis of Hymenoptera Venom Allergy (HVA), (ii) the specific role of occupational exposure, (iii) the effect of Venom Immunotherapy (VIT) in reducing the severity of allergic episodes in workers exposed to repeated stings of hymenoptera, and (iv) the management of the occupational consequences caused by allergic reactions due to hymenoptera stings. METHODS: Between 2000 and 2013 an observational study, including patients referred to the regional reference hospital of Liguria, Italy, with an ascertained diagnosis of HVA and treated with VIT, was performed. A structured questionnaire was administered to all patients to investigate the occupational features of allergic reactions. These were graded according to standard systems in patients at the first episode, and after re-stings, during VIT. RESULTS: One-hundred and 8four out of the 202 patients referred had a complete data set. In 32 (17.4%) patients, the allergic reaction occurred during work activities performed outdoor. Of these, 31.2% previously stung by hymenoptera at work, and receiving VIT, were re-stung during occupational activity. The grades of reaction developed under VIT treatment resulted clinically less severe than of those occurred at the first sting (p-value = 0.031). CONCLUSION: Our findings confirmed the clinical relevance of HVA, and described its occupational features in outdoor workers with sensitization, stressing the importance of an early identification and proper management of the professional categories recognized at high risk of hymenoptera stings. The Occupational Physician should be supported by other specialists to recommend appropriate diagnostic procedures and the prescription of VIT, which resulted an effective treatment for the prevention of episodes of severe reactions in workers with a proven HVA.

Can serum white birch (Betula verrucosa) pollen antigen (Bet v 1) immunoglobulin E measurement distinguish between sensitization and allergy?

BACKGROUND: In clinical practice, it is fundamental to distinguish between sensitization and allergy, mainly with respect to polysensitized patients. The aim of this study was to evaluate whether serum immunoglobulin E (IgE) to white birch (Betula verrucosa) pollen antigen (Bet v 1) assessment might be able to differentiate simple sensitization from true allergy. METHODS: In total, 197 subjects (100 females; mean age 44.9 years) with serum Bet v 1 IgE positivity and history of nasal symptoms were evaluated. Subjects were subdivided in 2 groups: allergic and sensitized. RESULTS: Allergic patients were 58.4% of the total; they had higher serum Bet v 1 IgE levels than sensitized subjects (p < 0.001). A serum IgE to Bet v 1 value >8.94 kilo units of allergen per liter (kUA/L) was able to differentiate between sensitization and allergy (area under the receiver operating characteristic curve [AUC] = 0.76; diagnostic odds ratio, ie, degree of agreement between health status and dichotomized IgE levels [DOR] = 6.5). Gender and season when the blood was drawn influenced IgE levels. CONCLUSION: Serum Bet v 1 IgE measurement may be able to differentiate sensitization from allergy in subjects with sensitization to Betulaceae pollen allergens. Thus, Bet v 1 IgE measurement should be considered a useful step in the management of patients with allergic rhinitis due to Betulaceae pollen allergens.

Nickel oral hyposensitization in patients with systemic nickel allergy syndrome.

BACKGROUND: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with "systemic nickel allergy syndrome" (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. METHODS: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 µg, 0.3 µg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5(th) month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. RESULTS: During Ni-rich food re-introduction, the 1.5 µg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 µg Ni/week than placebo (p = 0.05). Patients reported no side-effects. CONCLUSIONS: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.

Effectiveness of high dose sublingual immunotherapy to induce a stepdown of seasonal asthma: a pilot study.

BACKGROUND: There is ample evidence to support the efficacy of sublingual immunotherapy (SLIT) on allergic rhinitis, while there is less solid data regarding asthma. We evaluated the effects of a high dose birch SLIT on birch-induced rhinitis and asthma in a controlled study. METHODS: This double-blind, placebo-controlled, randomised, single centre trial on SLIT with birch pollen allergen extract (Stallergenes, Antony, France) included 24 patients presenting severe rhinitis and slight to moderate asthma, 14 actively and 10 placebo treated. SLIT was performed by a pre-coseasonal protocol, and was repeated for 2 years. The study plan included a selection visit, a visit at the start of the first and the second treatment cycle, a follow-up visit after 1-3 months from the start of each cycle, and a final visit at the end of each yearly cycle. RESULTS: A significant decrease (p < 0.05) in rhinorrhoea and nasal obstruction occurred in actively treated patients. The median number of days with asthma at visit 3 was 10 (0-27) in the active (SLIT) group and 13 (0-29) in the placebo group. The median number of days with asthma at visit 6 was 2 (0-6) in the SLIT group and 7 (0-15) in the placebo group (p < 0.05 between groups). A stepdown of asthma occurred in 77% of actively treated vs. none of placebo treated patients (p = 0.05). No severe adverse events were observed. CONCLUSIONS: This pilot study suggests that SLIT with high dose birch extract may be able to step down seasonal pollen-induced asthma after prolonged treatment.