Exercise-induced anaphylaxis: A clinical view

Povesi Dascola and Caffarelli Italian Journal of Pediatrics 2012, 38:43 http://www.ijponline.net/content/38/1/43 REVIEW ITALIAN JOURNAL OF PEDIATRICS Open Access Exercise-induced anaphylaxis: A clinical view Carlotta Povesi Dascola and Carlo Caffarelli* Abstract Exercise-induced anaphylaxis (EIA) is a distinct form of physical allergy. The development of anaphylaxis during exertion often requires the concomitant exposure to triggering factors such as intake of foods (food dependent exercise-induced anaphylaxis) or drugs prior to exercise, extreme environmental conditions. EIA is a rare, but serious disorder, which is often undetected or inadequately treated. This article summarizes current evidences on pathophysiology, diagnosis and management. We reviewed recent advances in factors triggering the release of mediators from mast cells which seems to play a pathogenetic role. A correct diagnosis is essential to avoid unnecessary restricted diet, to allow physical activity in subjects with EIA dependent from triggering factors such as food, and to manage attacks. An algorithm for diagnosing EIA based on medical history, IgE tests and exercise challenge test has been provided. In the long-term management of EIA, there is a need for educating patients and care-givers to avoid exposure to precipitating factors and to recognize and treat episodes. Future researches on existing questions are discussed. Keywords: Physical exercise, Food allergy, Exercise-induced anaphylaxis, Exercise-induced bronchocostriction, Urticaria, Anaphylaxis Introduction Physical exercise may provoke the onset of clinical symptoms that are usually due to an allergic reaction. Distinct forms of recognized physical allergies are exercise-induced anaphylaxis (EIA), cholinergic urticaria, exercise-induced bronchospasm and rhinitis. Anaphylaxis triggered by physical exertion is a serious disorder which is often undetected or inadequately treated. EIA is rare, with a prevalence of 0.048% in a survey of 76.229 adolescents, aged 13–15 years [1]. Up to 9% of children referred to a tertiary allergy center for anaphylaxis suffer from EIA [2]. EIA affects subjects at any time during lifespan and age of onset varies from 4 to 74 years [3,4]. Concomitant factors may be required to develop anaphylaxis during exertion. In 30% [1] - 50% of cases [3], EIA occurs only when the subject ingests a particular food before exercise, known as specific food dependent exercise-induced anaphylaxis (FDEIA) [5] or a meal (non-specific FDEIA) prior to exercise [6]. Angioedema and oral allergy syndrome have been reported in an 8 years-old boy who ingested tomatoes * Correspondence: Clinica Pediatrica, Dipartimento di Medicina Clinica e Sperimentale, Azienda Ospedaliera-Universitaria di Parma, Università degli Studi di Parma, Via Gramsci 14, Parma, Italy after physical exercise [7]. Exercise or food alone do not elicit symptoms. Maulitz et al. [5] described the first case of shellfish dependent EIA in 1979. Afterwards, many different types of foods have been reported to predispose the development of EIA. They include celery [8], wheat [9-11], shellfish [12], grapes [11], nuts [13], peaches [13], eggs [14,15], oranges [16], apples [17], hazelnuts [18], chees [19], cabbage [3], chestnuts [20], rice [20], tomatoes [20], cuttlefish [21], pistachios [22], cow’s milk [23], corn, paprika, mustard, barley [24], onions [25], peanuts [15,26], fish [27], snails [28], pork [29], beef [29], chicken/turkey [30], mushrooms [31], buckwheat [32], alcohol [3]. Some patients are sensitive to more than one type of food [20]. In some patients with FDEIA, aspirin intake [33], cold [34] or warm environment [35] are required for developing the reaction. FDEIA may occur only when two types of foods are simultaneously ingested before exercise [29,36]. Moreover, during cow’s milk desensitization, children may have cow’s milk dependent EIA episodes [37]. In many patients with EIA, food intake is not related to EIA occurrence but other precipitating factors have been reported. They are drugs [3,5,8,38], cold or warm temperature, humidity [3,38-40], menstrual cycle [11], dental amalgam [40], pollen season [3], ingestion of dust mites contained in © 2012 Povesi Dascola and Caffarelli; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Povesi Dascola and Caffarelli Italian Journal of Pediatrics 2012, 38:43 http://www.ijponline.net/content/38/1/43 contaminated foods [41]. A family history of EIA has been associated with the HLA A3B8DR3 [42] or with a possible autosomal dominant inheritance [43]. Subjects with EIA or FDEIA [44] are often atopic. These findings might suggest a potential genetic origin for EIA. Pathophysiology In EIA, the release of vasoactive mediators from mast cells may play a pathogenetic role. This has been observed in skin biopsies [45] and it has been confirmed by findings of increased serum histamine [45-47] and tryptase [48] levels in patients with EIA after exercise. Release of mast cell mediators may result in vascular leakage, inflammatory cell recruitment and occurrence of anaphylaxis [49]. The mast cell degranulation may be mediated by IgE antibodies. However, in patients with EIA, serum IgE antibodies are usually normal in patients who do not suffer from allergic diseases [50]. Other triggering factors may be lactate or creatinine phosphokinase [51]. Overall, it remains unclear which factors trigger mast cell degranulation. In patients with FDEIA, the ingestion of the offending food alone does not provoke clinical hypersensitivity reactions, even if IgE antibodies against the causative food allergens are usually detected by skin prick tests or in the serum. Non mutually exclusive explanations have been provided for the loss of tolerance to food during exercise [52]. Some of them are sustained by clinical findings. First, the administration of sodium bicarbonate before physical activity prevents occurrence of symptoms in patients with FDEIA [53]. Therefore it has been suggested that pH modifications might elicit the onset of anaphylaxis. Along this line, it has been reported that after physical activity, pH decreases both in serum and in muscle [54,55]. Furthermore, a reduced pH enhances mast cell degranulation [56]. Second, aspirin appears to induce anaphylactic reaction to wheat by increasing gastrointestinal permeability. This is suggested by the fact that in patients with wheat dependent EIA, both wheat-exercise and wheat-aspirin challenges provoked an increased gliadin absorption and allergic symptoms. Higher serum gliadin levels may cause degranulation of mast cell with onset of anaphylaxis [57]. Small intestinal permeability is increased by exercise [58]. However, it has be (...truncated)