Wheat Anaphylaxis Due to Skin Contact in an Exclusively Breastfed

Practitioner's Corner 62

3. Smith PK, O’B Hourihane J, Lieberman P. Risk multipliers for severe food anaphylaxis. World Allergy Organ J. 2015 Nov Wheat Anaphylaxis due to Skin Contact in an 24;8(1):30. Exclusively Breastfed 2.5-Month-Old Infant 4. Kim NY, Kim GR, Kim JH, Baek JH, Yoon JW, Jee HM, et al. Food allergen sensitization in young children with typical signs and Sadri H1,2, Fazlollahi MR2, Shokouhi Shoormasti R2, Pourpak Z2 symptoms of immediate type food allergies: A comparison 1Department of Allergy and Immunology, Emam Ali Hospital, between monosensitized and polysensitized children. Korean Alborz University of Medical Sciences, Karaj, Iran J Pediatr. 2015 Sep;58(9):330-5. 2Immunology, Asthma and Allergy Research Institute, Tehran 5. Niggemann B, Beyer K. Factors augmenting allergic reactions. University of Medical Sciences, Tehran, Iran Allergy. 2014;69:1582-7. J Investig Allergol Clin Immunol 2019; Vol. 29(1): 62-64 doi: 10.18176/jiaci.0332

Key words: Specific IgE. Wheat. Anaphylaxis. Skin contact.

Manuscript received August 22, 2018; accepted for publication Palabras clave: IgE específica. Trigo. Anafilaxia. Contacto cutáneo. September 25, 2018.

Martha Cabrera Sierra Servicio de Alergia Hospital los Madroños Anaphylactic reaction induced by contact between the Carretera M-501, Km 17,9 skin and food allergens is rare in infants. To the best of our 28690 Brunete, Madrid knowledge, there have been no reported cases of anaphylactic E-mail: [email protected] reaction following skin exposure to wheat in infants, although rare cases of anaphylaxis have been reported after skin contact with peanut, milk, egg, and fish [1]. We report a case of anaphylaxis resulting from skin contact with wheat in an infant. A 2.5-month-old boy experienced generalized urticaria, breathing difficulty, lethargy, cyanosis around the mouth, acrocyanosis, and severe penis swelling about 5 minutes after contact of the penis with a mixture of wheat dough and animal fat. He was circumcised when he was 1 month old and had developed skin adhesions at the site. According to a traditional belief, this combination relieves skin adhesion and problems associated with circumcision. His parents washed his penis immediately after the anaphylactic reaction and went to the emergency department. Following therapy with epinephrine, corticosteroids, and fluid resuscitation, he was referred to our hospital, where he was seen by an allergist–clinical immunologist. The patient was born through cesarean delivery (birth weight, 3700 g). Following umbilical cord separation on the eighth day after birth, the aforementioned mixture was placed on the site of umbilical cord. A few minutes later, he began to experience severe vomiting, although no redness was observed around the umbilical cord. He was exclusively breastfed, and his mother was not on a specific diet. He has had recurrent vomiting and drooling since the neonatal period, suggesting a diagnosis of gastroesophageal reflux disease. His mother had a history of allergic rhinitis, and his 3-year- old brother had experienced localized urticaria following an insect bite. A physical examination at 2.5 months of age revealed his weight to be 6 kg, and the only positive finding was mild atopic dermatitis on the cheeks. Three days after the diagnosis of anaphylaxis, the specific IgE concentration was measured using the RIDA qline Allergy test for food allergens (R-Biopharm) and ImmunoCAP

(Thermo Fisher Scientific) for wheat and its allergens, It was recently suggested that wheat allergy, contact including ω-5 gliadin (rTri a 19) and lipid transfer protein urticaria, and wheat-dependent exercise-induced anaphylaxis (rTri a 14). could develop in adults as a result of using soaps containing The RIDA qline Allergy test showed positive specific hydrolyzed wheat proteins [4,7]. However, this type of IgE only to wheat (8.62 IU/mL). In addition, the specific IgE sensitization has not yet been reported in infants. concentration to wheat was 55.8 kU/L using ImmunoCAP. Two factors were involved in the onset of anaphylaxis The results of the molecular diagnosis showed a specific IgE after skin exposure in the present case. The first was the high concentration of 1.88 and <0.10 kU/L for ω-5 gliadin and concentration of specific IgE to the wheat allergen before age lipid transfer protein, respectively. Furthermore, specific IgE 3 months and the higher clinical relevance of lower levels of (kU/L) to other cereals was as follows: barley, 2.94; rice, <0.10; specific IgE at lower ages [8]. The other is that the wheat was and maize, 0.17. The white blood cell count was 7100, the raw (cooking can reduce its allergenicity) [9]. eosinophil percentage was 5.2%, and total IgE was 139 IU/ Specific IgE to barley was positive, possibly as a result of mL. The patient was prescribed avoidance of gluten-containing strong cross-reactivity between wheat and barley. Moreover, food and EpiPen for emergency situations. specific IgE to rice and maize was negative. This finding had At 4 months of age, the parents declared that the child had been demonstrated in a previous study. Both rice and maize experienced severe vomiting after a short stop in front of a bakery. can be recommended as alternative cereals [10]. The RIDA qline Allergy test was repeated with a food The RIDA qline Allergy test and ImmunoCAP were allergen panel at 4 months of age and revealed specific IgE to performed 3 and 45 days after the anaphylactic reaction. wheat (0.34 IU/mL). In addition, specific IgE to other allergens Specific IgE to wheat decreased rapidly after allergen was negative. Specific IgE to wheat was also assessed using avoidance. Therefore, it can be concluded that in vitro tests ImmunoCAP, although the concentration was significantly are most sensitive early after the anaphylactic reaction. lower than the first time (15.9 kU/L). Anaphylactic reactions have been reported in exclusively Funding breastfed infants. These could be due to the transmission of The authors declare that they did not receive funding for food allergens from breast milk or exposure through skin or the present study. the respiratory tract [2]. Sporadic cases of anaphylactic reaction resulting from Conflicts of Interest skin contact have been reported mainly in children with atopic dermatitis who come into contact with egg, milk, fish, The authors declare that they have no conflicts of interest. and peanut [1]. All cases of wheat anaphylaxis, including those recorded in Iran, occurred after direct feeding with wheat [3]. References Wheat products are usually introduced to infants at 4-6 months; however, allergic sensitization can occur before 1. Tan BM, Sher MR, Good RA, Bahna SL. Severe food allergies by direct feeding of wheat via the passage of allergen from breast skin contact. Ann Allergy Asthma Immunol. 2001;86(5):583- milk [4]. The failure to develop an anaphylactic reaction in 6. spite of the transmission of wheat allergen from breast milk 2. Lifschitz CH, Hawkins HK, Guerra C, Byrd N. Anaphylactic can result from allergen-immunoglobulin immune complexes shock due to cow's milk protein hypersensitivity in a breast- in breast milk [5]. In addition, oral tolerance may be induced fed infant. J Pediatr Gastroenterol Nutr. 1988;7(1):141-4. in infants through very low amounts of gluten in breast milk. 3. Pourpak Z, Ghojezadeh L, Mansouri M, Mozaffari H, It was recently suggested that skin contact with food proteins Farhoudi A. Wheat anaphylaxis in children. Immunol Invest. can bring about the penetration of food allergens through 2007;36(2):175-82. the disrupted skin barrier, for example, in atopic dermatitis. 4. Quirce S, Boyano-Martinez T, Diaz-Perales A. Clinical Presentation of an allergen to cutaneous Langerhans cells can presentation, allergens, and management of wheat allergy. result in the induction of TH2 responses and, subsequently, Expert Rev Clin Immunol. 2016;12(5):563-72. the production of allergen-specific IgE by B cells, while low 5. Lack G. Update on risk factors for food allergy. J Allergy Clin transmission of food allergens in breast milk can induce oral Immunol. 2012;129(5):1187-97. tolerance [5]. 6. Edelbauer M, Loibichler C, Nentwich I, Gerstmayr M, Urbanek According to this hypothesis, the anaphylactic reaction R, Szepfalusi Z. Maternally delivered nutritive allergens in cord in the case we report could be attributed to contact with the blood and in placental tissue of term and preterm neonates. wheat allergen at 8 days of age. However, the onset of severe Clin Exp Allergy. 2004;34(2):189-93. vomiting after skin contact with wheat at the age of 8 days is 7. Scibilia J, Rossi CM, Losappio LM, Mirone C, Farioli L, Pravettoni still open to discussion. As a result, it seems that the patient had V, et al. Wheat food allergy in adults has a favorable prognosis. already been exposed to the wheat allergen and presentation of J Investig Allergol Clin Immunol. 2018;29(2). In press. the allergen to the patient’s immune system and sensitization 8. Komata T, Soderstrom L, Borres MP, Tachimoto H, Ebisawa occurred before 8 days of age, perhaps even in utero, as low M. The predictive relationship of food-specific serum IgE quantities of allergen were detected in the placenta and cord concentrations to challenge outcomes for egg and milk varies blood in a study by Edelbauer et al [6]. by patient age. J Allergy Clin Immunol. 2007;119(5):1272-4.

9. Varjonen E, Bjorksten F, Savolainen J. Stability of cereal allergens. Clin Exp Allergy. 1996;26(4):436-43. Role of Creatine Kinase as an Allergen in Immediate 10. Pourpak Z, Mesdaghi M, Mansouri M, Kazemnejad A, Toosi Selective Allergy to Pork Meat SB, Farhoudi A. Which cereal is a suitable substitute for wheat in children with wheat allergy? Pediatr Allergy Immunol. Barbarroja-Escudero J1, Sánchez-González MJ1, Pineda F2, 2005;16(3):262-6. Rodríguez-Rodríguez M1, Castillo M2, Alvarez-Mon M1 1Servicio de Enfermedades del Sistema Inmune-Alergia, Hospital Universitario Príncipe de Asturias, Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain 2Application Department, Diater Laboratories, Madrid, Spain Manuscript received June 20, 2018; accepted for publication October 1, 2018. J Investig Allergol Clin Immunol 2019; Vol. 29(1): 64-66 doi: 10.18176/jiaci.0333 Zahra Pourpak Immunology, Asthma and Allergy Research Institute Tehran University of Medical Sciences Key words: -Gal. Creatine kinase. Dry-cured ham. Pork meat. Selective P.O. BOX 14185-863, Tehran, Iran allergy. E-mail: [email protected] Palabras clave: Alfa-gal. Creatina quinasa. Jamón. Carne de cerdo. Alergia selectiva.

Allergic reactions can occur after ingestion of pork products [1]. Allergy to pork meat is very uncommon in isolation [2]. We present a protein identified in a series of patients with selective allergy to pork-derived foods. Six patients were recruited for an allergy work-up between January 2014 and February 2016. They all tolerated other mammalian meats, poultry, fish, and condiments/spices. Only patient #4 reported a tick bite. No patient had received cetuximab or a gelatin-derived colloid. Skin prick testing was performed using a subset of indoor and outdoor aeroallergens (pollens, molds, mites, dog, cat, hamster, rabbit, horse, and cow), along with a food battery (Anisakis, profilin, lipid transfer protein, latex, and spices) and a meat battery (pork, beef, lamb, rabbit, and chicken) (ALK-Abelló). Prick-by-prick tests were performed for raw and boiled meats (pork, beef, lamb, rabbit, chicken, and turkey), ham (cooked and dry-cured), and other pork-derived foods (chorizo, sausage, salami, and loin), with negative controls (50% glycerinated saline) and positive controls (histamine hydrochloride, 10 mg/mL). Prick-by-prick testing with bovine gelatin-derived colloid (Aventis Pharma) and additional intradermal testing with a 1:100 dilution of bovine gelatin-derived colloid were performed in order to rule out possible asymptomatic gelatin sensitization. Serum total IgE and specific IgE against meats (pork, beef, lamb, and chicken), a-gal, gelatin, and bovine serum albumin, were measured using ImmunoCAP (Thermo Fisher Scientific) following the manufacturer’s instructions. All clinical data are shown in the Supplementary Table. All patients had negative results in skin tests with bovine gelatin-derived colloid. Five nonatopic and 5 atopic individuals served as controls, and they all had negative results to skin tests with meat, including pork. In order to identify the culprit protein, proteins from dry- cured ham were separated by SDS-PAGE according to the method of Laemmli [3] (Figure) and electrotransferred onto polyvinylidene fluoride membranes as previously described by