M.L. Baeza

Characterization of allergens secreted by Anisakis simplex parasite: clinical relevance in comparison with somatic allergens

Background Diagnostic methods for the study of allergic reactions to Anisakis simplex (A.s.) based on whole‐body extracts of the larva are clearly insufficient.

Histamine releasing factors and cytokine-dependent activation of basophils and mast cells

Publisher Summary This chapter describes the various types of histamine releasing factors (HRFs), discusses their interaction with basophils or mast cells, and speculates regarding their role in inflammation in general, and in allergic diseases in particular. The release of histamine from human basophils or mast cells is typically initiated by the interaction of antigen with surface-bound immunoglobulin (IgE) antibody. Histamine releasing factors are defined as products of activated cells that interact with basophils and mast cells to cause the release of histamine. Two general types of HRFs is described, one whose function appears to be dependent upon cell surface IgE and others that are IgE independent. A variety of reports confirmed that lymphoid cells produce such a factor, and HRF-like activities are described as products of T lymphocytes, mixed mononuclear cells, alveolar macrophages, platelets, B lymphocytes, and neutrophils. Such activity also appeared to be present in nasal washings of allergic subjects and in antigen-challenged cutaneous late-phase reactions. Histamine releasing factors cause a noncytotoxic granule exocytosis from basophils when assessed by electron microscopy and cause histamine release as well as release of lipid mediators such as leukotriene C4.

Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing

We studied 28 patients with fixed drug eruption (FDE) caused by sulfonamide antibiotics to investigate cross‐reactivity between sulfonamide derivatives and p‐amino compounds and to explore the usefulness of patch testing, as an alternative to controlled oral challenge testing (COCT), in diagnosis within this clinical area. COCT with sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethizole (SMZ), furosemide (FU), procaine (PRO) and glipizide (GPZ) was performed. Patch testing (PT) with SMX and SDZ was carried out. In all patients, the diagnosis of FDE was confirmed by positive COCT and allergy to trimethoprim ruled out by COCT. 42.8 and 31.8% of the SMX‐induced FDE patients reacted to SMZ and SDZ, respectively. All patients (n = 28) tolerated FU, PRO and GPZ. COCT performed with the 3 sulfonamide antibiotics in 12 patients was positive in 2 subjects with the 3 drugs, in 2 patients only with SMX and SMZ and in the remaining 8, SMX was the only causative drug. PT was positive in 5 of 25 patients positive on COCT. The probability of obtaining a positive PT was higher among patients who had a residual lesion than that among those who lacked this. Cross‐reactivity between different sulfonamide antibiotics is thus variable, being most likely between SMX and SMZ. We have found no cross‐reactivity between sulfonamide antibiotics and other sulfonamide derivatives or p‐amino drugs in FDE. PT is a useful tool in the diagnosis of FDE, especially if there are residual lesions, because it avoided the need for COCT in 20% of patients.

Anisakis simplex-sensitized patients: should fish be excluded from their diet?

BACKGROUND Anisakis simplex (A.s.) allergy is an emerging disease. The third-stage larvae of this nematode are a source of hidden allergens in fish. There are no clear guidelines concerning dietary restrictions for patients with serum-specific IgE to this parasite. OBJECTIVE To follow up the clinical data and immunological parameters of patients sensitized to A.s. during 6 to 23 months. METHODS The clinical symptoms and serologic status of 17 patients with specific IgE and positive skin prick test results to A.s. were studied prospectively. Six of these had anaphylaxis (ANA) attributed to A.s. and 11 patients experienced concomitant chronic urticaria (CU). All patients were advised not to eat fish for 6 months. RESULTS Four patients from the ANA group excluded fish, and ANA did not recur. Two other patients with ANA refused to exclude fish; one remained free of symptoms and the other experienced several urticarial episodes. During this 6-month period total IgE levels decreased in all six ANA patients; specific IgE for A.s. decreased in four patients and increased in two. Two patients from the CU group did not exclude fish, and symptoms persisted in these two patients. Clinical improvement was observed in 78% of the patients with CU who excluded fish. Total and specific IgE levels decreased in all the patients with CU. CONCLUSIONS Because ANA symptoms are very severe, patients should always be advised to exclude fish until specific food allergens are identified. However, in patients with CU and specific IgE to A.s., only the clinical response to fish ingestion will determine the need for strict fish avoidance.

Urticaria due to mepivacaine with tolerance to lidocaine and bupivacaine

tion) to which he had no reaction. Modified radioallergosorbent test (RAST) testing was performed with the patient’s serum to naproxen and no specific IgE was identified (Quest Diagnostics, Teterboro, NJ, USA). He was also skin-prick tested to 1/100, 1/10 and full-strength liquid naproxen (125 mg/5 ml), without wheal and flare reaction. This case demonstrated reproducible anaphylaxis to naproxen without cross reactivity to rofecoxib, aspirin or ibuprofen. Without this patient’s insistence and his professional and athletic performance requirements we would not have challenged him with naproxen, but would have challenged him with the later three drugs to provide his alternative NSAIDs. Anaphylaxis to naproxen is not rare. A recent study by van Puijenbroek (3), reported naproxen as the second leading cause of NSAID-induced anaphylaxis between 1985 and 2000 in the Netherlands. The mechanism of the reaction to naproxen is not well defined. A case report by Cisterno (4), in 1983, reported a positive intradermal skin test in a naproxen specific anaphylaxis case. This same report also demonstrated a positive basophil release assay to naproxen. To date, there have been rare reports of cross-reactions to NSAIDS in normal individuals who have anaphylaxis (1). Although we used liquid naproxen for challenge, we feel his reaction on challenge was consistent with his prior reaction and is specific for naproxen. We have been unable to demonstrate naproxenspecific IgE either by RAST or skin testing but this does not rule out the probability that an IgE-mediated reaction occurred.

Pollen‐induced airway inflammation, hyper‐responsiveness and apoptosis in a murine model of allergy

Background Previous studies indicate that murine models are useful tools for studying the allergic diseases, including certain aspects of bronchial asthma such as cellular tissue inflammation and pulmonary function.

Factor XII gene missense mutation Thr328Lys in an Arab family with hereditary angioedema type III.

1. Kurth BM, Kamtsiuris P, Hölling H, Schlaud M, Dölle R, Ellert U et al. The challenge of comprehensively mapping children’s health in a nation-wide health survey: design of the German KiGGS Study. BMC Public Health 2008;8:196. 2. Schlaud M, Atzpodien K, Thierfelder W. Allergic diseases. Results from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007;50:701– 710. 3. Gotthard Mortz C, Andersen KE, BindslevJensen C. The prevalence of peanut sensitization and the association to pollen sensitization in a cohort of unselected adolescents – The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Pediatr Allergy Immunol 2005;16:501–506. 4. Asarnoj A, Östblom E, Ahlstedt S, Hedlin G, Lilja G, van Hage M et al. Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen – results from the BAMSE birth cohort. Allergy 2010;65:213–219. 5. Ben-Shoshan M, Harrington DW, Soller L, Fragapane J, Joseph L, St Pierre Y et al. A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada. J Allergy Clin Immunol 2010; 125:1327–1335. 6. Asarnoj A, Movérare R, Östblom E, Poorafshar M, Lilja G, Hedlin G et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy 2010;65:1189–1195. Factor XII gene missense mutation Thr328Lys in an Arab family with hereditary angioedema type III

Anaphylaxis after eating figs

. THE fig (Ficus carica), which belongs to the family Moraceae and the genus Ficus, has been until now a rare cause of food allergy. Ficus benjamina, a member of the same family (1), known also as Java willow, Ceylon willow, or Bali’s fig tree, is used frequently to adorn public buildings and homes (2). We present the case of a 35-year-old woman who, in February 1997, immediately after eating a dried fig, presented palatine pruritus, sneezing, nasal obstruction, hydrorrhea, sore throat, sibilant dysnea, cough, and bilateral palpebral angioedema that ceased several hours after treatment with corticosteroids and epinephrine. She had tolerated the eating of figs up to that time and since then had not eaten any. She had had a specimen of F. benjamina in her house for around 6 years in 1996, after touching its leaves, she had suffered an episode of severe bilateral palpebral angioedema, watery eyes, ocular pruritus, and dry cough. Since then, she had also experienced blocked nose, hydrorrhea, watery eyes, and dry cough in her domestic environment, the symptoms disappearing when she left the house. Skin prick tests were positive with dried fig, skin and pulp of green fig, leaf and latex of F. benjamina (prick-prick), and commercial extract of fig (prick); they were negative with kiwi, banana, hops, chestnut, Hevea brasiliensis latex, common environmental pneumoallergens (prick), and Ficus lyrata (prick-prick). Total IgE was 23.6 kU/l. Specific IgE to fig was 4.2 kU/l; to H. brasiliensis latex, ,0.35 kU/l (CAP System, Pharmacia Diagnostics, Uppsala, Sweden). Spirometry gave values within reference limits. The nonspecific bronchial hyperreactivity test with histamine was positive (PC20: 0.63 mg/dl). SDS–PAGE immunoblotting (IgE) and inhibition were performed with extracts prepared by us with dried and fresh figs, and with F. benjamina (3). In SDS–PAGE immunoblotting, a band of 35 kDa was detected in dry fig and fresh fig. The F. benjamina extract contained two allergens of 35 and 19 kDa that were totally and partially inhibited by fresh and dried fig, respectively. The essay revealed crossreactivity between F. benjamina and fig (Fig. 1). The patient refused a bronchial challenge test with the extract of F. benjamina, claiming to be certain of the association between exposure and the symptoms she had presented. By our

Anaphylaxis in the Pediatric Emergency Department: Analysis of 133 Cases After an Allergy Workup

BACKGROUND Data on the incidence and characteristics of pediatric anaphylaxis are scarce. Reported causes of anaphylaxis are mostly those suspected by the physician in the emergency department (ED), which may not coincide with the real triggers. OBJECTIVES To investigate the incidence, management, and etiology of pediatric anaphylaxis in the ED of a Spanish tertiary hospital and to determine the concordance between the suspected etiology in the ED and diagnosis after the allergy workup. METHODS We performed an observational, descriptive study of all patients with anaphylaxis attended in the pediatric ED from 2012 to 2014. Cases were considered anaphylaxis based on National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria. We recorded data on clinical characteristics, management, etiology suspected by the ED physician and patient (or relatives), and the workup performed in the allergy department. RESULTS We recorded 133 cases of anaphylaxis (incidence, 0.12%), with 20 cases (15%) recorded in children younger than 12 months. Anaphylaxis was correctly diagnosed in the ED in 70 cases (53%). Food allergy was the cause of anaphylaxis in 106 out of 118 studied in the allergy department (AD) (90%). The final etiology differed from the etiology initially suspected in the ED in 42 cases (39%). After the study, the frequency of patients with unidentified triggers decreased by 75%. CONCLUSIONS The incidence of anaphylaxis is higher in children than previously reported in adults from the same center, and food is the trigger in most cases. To prevent erroneous diagnoses, the etiology of anaphylaxis should be established after an appropriate workup.

Management of Pregnancy and Delivery in Patients With Hereditary Angioedema Due to C1 Inhibitor Deficiency.

BACKGROUND AND OBJECTIVE There is little information on pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency (C1INH-HAE). The aim of this study was to describe the effect of pregnancy and deliveries on symptoms of C1INH-HAE and review the need for and safety of treatments available during the study period. METHODS Retrospective review using a purpose-designed questionnaire of 61 C1INH-HAE patients from 5 hospitals specialized in the management of HAE in Spain. The outcomes measured were number of pregnancies, changes in symptoms during pregnancy and delivery, mode of delivery, type of anesthesia during delivery, treatments received, and tolerance of treatments. RESULTS We reviewed 125 full-term pregnancies (89 without a prior diagnosis of C1INH-HAE), 14 miscarriages, and 4 induced abortions. Patients reported an increased frequency of C1INH-HAE symptoms in 59.2% of pregnancies (74/125) and the presence of symptoms throughout pregnancy in 40% (50/125). Prophylactic C1INH-HAE therapy was used during 9 (7.2%) of the 125 pregnancies. Nine patients--in 11 pregnancies (8.8 %)--received treatment for acute attacks. Most deliveries (n=110, 88%) were vaginal. A cesarean section was necessary in 15 cases (12%). Short-term prophylaxis with pdhC1INH was administered before 14 deliveries (11.2 %); 111 deliveries (88.8 %) were performed without premedication and were well tolerated. Anesthesia was used in 51 deliveries (40.8%). CONCLUSIONS Pregnancy has a variable influence on the clinical expression of C1INH-HAE. Attacks tend to occur more frequently but not to increase in severity. Vaginal delivery was mostly well tolerated. pdhC1INH prophylaxis should be administered prior to cesarean delivery and is also recommended before vaginal delivery if there are additional risk factors. pdhC1INH should always be available in the delivery room.