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maleate at 4 mg/mL [Fenistil injectable solution, Novartis]), Anaphylaxis to Dimenhydrinate Caused by the
2 piperazines (cetirizine hydrochloride at 10 mg/mL [Zirtek Theophylline Component
tablet in normal saline, UCB] and levocetirizine dihydrochloride at 5mg/mL [Xozal tablet in normal saline, UCB]) and a piperidine (desloratadine at 5mg/mL [Aerius tablet in normal Allergy Department, Laikon General Hospital, Athens, Greece saline, Schering-Plough]). All were negative. To study the allergenic properties of the 2 compounds Key words: Anaphylaxis. Dimenhydrinate. Diphenhydramine. Drug we proceeded to perform SPTs with the pure substances (Figure). Interestingly, there was no reaction when we tested Palabras clave: Anafi laxia. Dimenhidrinato. Difenhidramina. diphenhydramine (1 mg/mL, 10 mg/mL, and 100mg/mL; powder provided by Recordati, Italy), as previously reported [3]. In contrast, all the theophylline-containing drugs tested were positive. Specifically, we tested anhydrous theophylline (0.6 mg/mL, 6 mg/mL, and 60mg/mL [Theodur tablet in normal saline, Lavipharm]), choline theophyllinate (0.8 mg/mL, Dimenhydrinate is an over-the-counter, widely used drug 8mg/mL, and 80 mg/mL [Choledyl syrup, Galenica]), and for motion sickness. It consists of 2 drugs: diphenhydramine, an aminophylline (0.25 mg/mL, 2.5 mg/mL, and 25 mg/mL ethanolamine, and 8-chlorotheophylline, a xanthine derivative [injectable solution, Cooper]). The results were increasingly that reduces the sedating properties of diphenhydramine. positive. Again, 5 healthy individuals tested negative. Of Allergic reactions to dimenhydrinate are rare and typically interest, SPTs for allopurinol (3 mg/mL, 30 mg/mL, and manifest as fi xed drug eruptions [1,2]. To our knowledge, no 300 mg/mL [Zylapour tablet in normal saline, Farmanic]), episodes of anaphylaxis have been reported. which is a structural isomer of hypoxanthine resembling Herein, we present the case of a 27-year-old woman who theophylline, were negative. It can be concluded thus that was admitted with sudden pruritic rash on the palms that rapidly the reactivity in our patient was specifi c to the theophylline progressed to the soles and the fl exural surface of the elbows. compound. Unfortunately, the patient refused to undergo Within 30 minutes, she developed emesis, diarrhea, and pain in a diagnostic oral drug challenge. Of note, previous reports the lower abdomen. The symptoms resolved without treatment on aminophylline reactivity have not been attributed to within an hour. Ten minutes prior to the onset of the rash, she had theophylline but rather to ethylenediamine, a well-known taken an antiemetic pill (50 mg dimenhydrinate) due to a planned car trip. She reported multiple intakes of dimenhydrinate in the past without any reaction. History was insignifi cant for other allergic disease, with no reports of atopic dermatitis, physical urticaria, or food or drug allergy.
Based on the concurrent manifestation of symptoms affecting the skin and the gastrointestinal tract together with the pain in the lower abdomen (attributed to uterine contractions), we considered the possibility of an anaphylactic reaction to dimenhydrinate and proceeded to perform skin prick tests (SPTs) with the suspected agent. The tests were performed with increasing concentrations (0.5 mg/mL, 5 mg/mL, and 50 mg/mL) of dimenhydrinate (Drimen tablet in normal saline, Coup); they were all positive with progressively increasing wheal and fl are reactions. The same tests performed in 5 healthy controls were negative, indicating no irritating effect of the drug. SPTs performed with a panel of food allergens (egg white, cow’s milk, wheat, and fi sh) and aeroallergens (grass mix, weed mix, Olea europea, Parietaria judaica, cat epithelia, and Dermatophagoides pteronyssinus) were all negative, confi rming the negative atopic profi le of the patient. The Figure. Skin prick tests, performed using the standard prick method, patient did not exhibit dermographism. To assess the specifi city for the various compounds. DM indicates dimenhydrinate; DP, of the reaction, we performed SPTs with 4 antihistamines of diphenhydramine; AM, aminophylline; TH, anhydrous theophylline; CT, different drug classes. We tested an alkylamine (dimetindene choline theophyllinate; and AL, allopurinol. J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 In summary, this is the fi rst report of an anaphylactic reported species. More than half of these species occur in North reaction to dimenhydrinate attributed to 8-chlorotheophylline. America. Europe, however, is home to just 7 species and most Anaphylactic reactions to either theophylline or dimenhydrinate of them are currently endangered species. Crayfi sh is a very have not been previously reported. Moreover, SPTs seem to be popular food worldwide but few cases of adverse reactions a reliable method for detecting immunoglobulin E-mediated after its ingestion have been reported.
anaphylaxis to theophylline. Therefore, even though An 18-year-old woman presented with chest tightness, anaphylaxis to dimenhydrinate is very rare, the possibility of wheezing, headache, and hives on the abdomen that had such a reaction should be kept in mind, especially for patients appeared within minutes of eating Procambarus clarkii, a with high exposure in the past presenting with compatible crayfi sh belonging to the Cambaridae family. She said that symptoms. Finally, patients who develop anaphylactic she had never developed symptoms after eating crustaceans or reactions to dimenhydrinate should be instructed to avoid molluscs on previous occasions. As the only additional atopic xanthine derivatives without prior testing. background, she reported a history of pollen-induced seasonal Protein extracts from raw and boiled P clarkii shell (PCSr References
and PCSb, respectively) and fl esh (PCFr and PCFb) were prepared by homogenization in phosphate buffered saline, 1. Rodríguez-Jiménez B, Domínguez-Ortega J, González-García dialyzation, and lyophilization. Skin prick tests (SPTs) to JM, Kindelan-Recarte C. Dimenhydrinate-induced fi xed drug common commercial aeroallergens, crustaceans, molluscs, eruption in a patient who tolerated other antihistamines. J and Anisakis simplex were performed, with positive results Investig Allergol Clin Immunol. 2009;19:334-5. (wheal diameter ≥3 mm) only to grass and olea pollen. Prick- 2. Saenz de San Pedro B, Quiralte J, Florido JF. Fixed drug eruption by-prick tests with PCFr and PCFb yielded a wheal of 3 mm caused by dimenhydrinate. Allergy. 2000;55:297.
in both cases. Serum-specifi c immunoglobulin E (sIgE) against 3. Barranco P, López-Serrano MC, Moreno-Ancillo A. Anaphylactic commercial crab extract (Pharmacia CAP system) was <0.35 reaction due to diphenhydramine. Allergy. 1998;53:814.
kU/L, and sIgE determinations against PCSr, PCSb, PCFr, 4. Thompson PJ, Gibb WR, Cole P, Citron KM. Generalised allergic and PCFb (enzyme allergosorbent technique) yielded reactions to aminophylline. Thorax. 1984;39:600-3.
0.4 kU/L for PCSr (total IgE of 90 IU/mL) and were negative 5. Toal M, Kinney A, Fulton R. Allergy to the ethylenediamine for the rest of the extracts. All the extracts were analyzed by component of aminophylline. Ulster Med J. 1992;61:205-6.
sodium dodecyl sulfate polyacrylamide gel electrophoresis ❚ Manuscript received May 26, 2010; accepted for publication, November 18, 2010. Vasilios Vovolis
Allergy to Crayfi sh
D González-de-Olano,1 C Pastor-Vargas,2,3 M Gandolfo-Cano,1 E González-Mancebo,1 A Meléndez-Baltanás,1 MP Morales-Barrios,1 M Pérez-Gordo,4 F Vivanco,2,3 B Bartolomé51Allergy Unit, Hospital de Fuenlabrada, Madrid, Spain2Department of Biochemistry and Molecular Biology I, Universidad Complutense, Madrid, Spain 3Department of Immunology, Fundación Jiménez Díaz, Madrid, Spain4Allergy Unit, Fundación Jiménez Díaz, Madrid, Spain5Research & Development Department, Bial-Arístegui, Bilbao, Key words: Allergy. Crayfi sh. Ferritin.
Figure. Immunoglobulin (Ig) E-binding proteins in crayfi sh extracts. A, Palabras clave: Alergia. Cangrejo de río. Ferritina.
sodium dodecyl sulfate polyacrymidamide gel electrophoresis (SDS-PAGE) IgE-immunoblotting of raw Procambarus clarkii fl esh. B, SDS-PAGE IgE-immunoblotting of raw P clarkii shell. Lane P, patient serum; lane Crayfi sh, also known as crawfi sh or crawdad, are crustacean C, control serum (pool of sera from nonatopic individuals); lane M, members of the Astacoidea and Parastacoidea superfamilies. Distributed throughout the world, there are more than 500 J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 (SDS-PAGE) as described by Laemmli [1], showing protein ferritin, from the snail Lymnea stagnalis L. Eur J Biochem. bands ranging between 14 and 99 kDa for the PCFr and PCSr extracts. SDS-PAGE IgE-immunoblotting assays revealed 6. Huang TS, Law JH, Söderhaäll K. Purifi cation and cDNA cloning IgE-reactivity with a 21-kDa protein in both extracts, but of ferritin from the hepatopancreas of the freshwater crayfi sh with stronger labeling in PCSr (Figure). In order to identify Pacifastacus Leniusculus. Eur J Biochem. 1996;236:450-6. this IgE-binding protein, the 21-kDa band from the PCSr extract was manually excised from the gel, digested with ❚ Manuscript received July 30, 2010; accepted for publication, trypsin, and analyzed by MALDI-TOF (matrix-assisted laser desorption/ionization-time-of-fl ight mass spectrometry) and LC-ESI-IT [liquid chromatography electrospray ionization David González de Olano
tandem mass spectrometry/LC-MS/MS]), as described by Pastor et al [2]. Protein identifi cation was performed by searching a nonredundant protein sequence database (NCBI) using the Mascot program (http://www.matrixscience.com). To identify the 21-kDa protein, we performed MS/MS and obtained the sequence of an internal peptide with the sequence AGTSGLGEFLFDKELK. Research conducted with protein databases identifi ed the sequence as ferritin.
Ferritin is a globular protein complex consisting of 24 protein subunits that is present in all cell types [3]. It is the Successful Rapid Rituximab Desensitization
primary intracellular iron-storage protein in prokaryotes and for Hypersensitivity Reactions to Monoclonal
eukaryotes and maintains iron in a soluble, nontoxic form. Antibodies in a Patient With Rheumatoid
In vertebrates, these subunits can be light-type (L) or heavy- Arthritis: A Remarkable Option
type (H) subunits, with a molecular weight of 19 kDa and 21 kDa, respectively [3]. An additional subunit resembling O Abadoglu,1 K Epozturk,1 E Atayik,1 E Kaptanoglu21Cumhuriyet University, Faculty of Medicine, Chest Diseases Lymnaea soma ferritin is associated with shell formation in the pearl oyster and its primary sequence is similar to that of Dept., Immunology and Allergic Diseases Subdepartment, the vertebrate H-type [4]. Because of the importance of iron in mineralization, ferritin is employed in the shells of organisms Cumhuriyet University, Faculty of Medicine, Rheumatology such as molluscs and crustaceans to control the concentration and distribution of iron, and to sculpt shell morphology and Key words: Desensitization. Rheumatoid arthritis. Rituximab.
coloration. The function and structure of ferritin vary by cell type and are controlled by an RNA-binding protein (iron- Palabras clave: Desensibilización. Artritis reumatoide. Rituximab.
regulatory protein). Ferritin sequences have been obtained in molluscs [5], and a ferritin subunit in the hepatopancreas of the freshwater crayfi sh Pacifastacus leniusculus has also been described [6]. To the best of our knowledge, however, no cases Rheumatoid arthritis (RA) is an infl ammatory disease of allergy to ferritin or crayfi sh have been reported. characterized by disturbances in T-cell and B-cell functions [1]. In this report, we present a case of IgE-mediated allergy Rituximab is a chimeric monoclonal antibody (mAb) against to P clarkii, a crayfi sh belonging to the Cambaridae family, CD20 that induces a profound depletion of B cells in the and suggest that the allergen involved was a 21-kDa protein.
peripheral blood of patients with RA [2]. The infusion of this mAb may cause transient hypotension or hypertension, cough, pruritus, and rash [3]. In 5% to 10% of cases, the reactions are References
clinically consistent with immediate hypersensitivity (IHS) reactions [4]. Desensitization to rituximab has been described 1. Laemmli UK. Cleavage of structural protein during assembly the head in case reports and small series of patients with hematologic of the bacteriophage T4. Nature. 1970; 227 (5259):680-5. malignancies and certain connective tissue diseases [5,6]. 2. Pastor C, Cuesta-Herranz J, Cases B, Pérez-Gordo M, Figueredo We report the case of a 32-year-old woman followed by our E, de las Heras M, Vivanco F. Identifi cation of major allergens in rheumatology department for RA for 7 years. In 2007, she had watermelon. Int Arch Allergy Immunol. 2009;149:289-90.
been given adalimumab (Humira, 40 mg/0.8 mL), an anti-tumor 3. Theil EC. Ferritin: stucture, gene regulation, and cellular function necrosis factor (TNF) mAb, in another medical center. After the in animals, plants, and microorganisms. Annu Rev Biochem. second dose (15 days after the fi rst dose), she developed labial angioedema and tongue swelling within 2 hours of injection. 4. Andrews SC, Arosio P, Bottke W, Briat JF, von Darl M, Harrison The following month, the medication was replaced by twice- PM, Laulhère JP, Levi S, Lobreux S, Yewdall SJ. Structure, function, weekly etanercept (Enbrel Pen, 50 mg), an anti-TNF fusion and evolution of ferritins. J Inorg Biochem. 1992;47:161-74. protein. After the fourth injection, she developed tingling in her lips, syncope, dizziness, and headache. Three months later, 5. von Darl M, Harrison PM, Bottke W. cDNA cloning and deduced the drug was withdrawn following epistaxis and bleeding in amino acid sequence of two ferritins: soma ferritin and yolk the mouth. Skin prick and intradermal tests with adalimumab J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 Table. Intravenous Desensitization Protocol for Rituximab were negative and the patient was therefore restarted on (Ig) E- or non-IgE–dependent mechanisms. Premedication adalimumab treatment. Nevertheless, after 6 months, she with antihistamines, acetaminophen, and/or corticosteroids presented erythema at the injection sites lasting more than is a common practice to prevent infusion reactions with all 24 hours. The drug was discontinued and the patient was hospitalized. Rituximab (Mabthera 500 mg/50 mL) therapy We present the first report of successful intravenous was planned and skin tests were performed with a drop (10 mg/mL) desensitization to rituximab performed in rapid succession for the prick test, and 0.03 mL of 1:100 and 1:10 dilutions (double desensitization) in a patient with RA. Although an for the intradermal test. All were negative. Rituximab was IgE-mediated mechanism was not confi rmed by skin tests, the administered and 90 minutes into the infusion (175 mg of the patient was empirically desensitized because the nature of the planned 1000-mg dose), the patient developed pruritic papular reactions indicated IHS. Rapid desensitization can be used for urticarial eruptions (which subsequently extended to the whole both IgE-mediated and non-IgE-mediated IHS reactions [6].
body), dizziness, tachycardia, and blackout. The infusion Rapid desensitization is a promising method for the was stopped; the patient was treated with antihistamines and delivery of rituximab after IHS reactions to mAbs and should intravenous steroids, and observed for several hours. After 1 be considered in RA when there are no acceptable therapeutic month, given the success of rituximab and the lack of response to other drugs, the patient agreed to be re-treated with rituximab Previous presentation: This case was presented as a
using a desensitization protocol. Written informed consent poster at the Turkish National Society of Allergy and Clinical was obtained and she was admitted to the immunology and Immunology Congress, November 3-7, 2010.
allergic diseases ward. She received premedication with an intravenous injection of 20 mg methylprednisone (Prednol-L) and an intramuscular injection of 45.5 mg/2 mL pheniramine References
(Avil) 30 minutes before the desensitization procedure. Three solutions in normal saline were prepared and delivered in 1. Martínez-Gamboa L, Brezinschek HP, Burmester GR, Dorner 12 consecutive steps as shown in the Table and described T. Immunopathologic role of B lymphocytes in rheumatoid in previous reports [6,7]. Hypertension occurred during the arthritis: rationale of B cell-directed therapy. Autoimmun Rev. infusion and the patient was treated with 10 mg amlodipine (Vasocard). Two weeks later, a second rituximab infusion was 2. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska administered within the desensitization protocol. Treatment A, Emery P, Close DR, Stevens RM, Shaw T. Effi cacy of B-cell schedules and concomitant medication for the underlying targeted therapy with rituximab in patients with rheumatoid disease were not altered during desensitization. The patient also arthritis. N Engl J Med. 2004;350:2572-81. received antihistamine and corticosteroid premedication 30 3. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska minutes before the second desensitization. The procedure was A, Emery P, Close DR, Stevens RM, Shaw T. Effi cacy of B-cell- successful and the patient subsequently tolerated rituximab. targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350(25):2572-81. The use of biological agents is increasing. RA remains the 4. Grillo-López AJ, White CA, Varns C, Shen D, Wei A, McClure A, only nonmalignant condition for which rituximab has received Dallaire BK. Overview of the clinical development of rituximab: approval from the US Food and Drug Administration [8]. mAbs fi rst monoclonal antibody approved for the treatment of can cause infusion-related reactions but the exact etiology of lymphoma. Semin Oncol. 1999 Oct;26(5 Suppl 14):66-73. these remains unclear. They can arise via immunoglobulin 5. Brennan PJ, Rodríguez Bouza T, Hsu FI, Sloane DE, Castells MC. J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 Hypersensitivity reactions to mAbs: 105 desensitizations in 23 and hand angioedema 10 minutes after the ingestion of a patients, from evaluation to treatment. J Allergy Clin Immunol. tablet of Cinfamar Cafeína (dimenhydrinate 50 mg and caffeine 50 mg) to prevent car sickness. She recovered spontaneously 6. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong in 2 hours and said that she had tolerated this drug on 5 DI, Laidlaw TM, Legere HJ, Nallamshetty SN, Palis RI, Rao JJ, previous occasions. Four months earlier, she had experienced Berlin ST, Campos SM, Matulonis UA. Hypersensitivity reactions a bronchospasm 2 hours after taking an ibuprofen tablet for to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. 2008;122(3):574-80.
Skin prick tests (SPTs) were performed, with negative 7. Brennan PJ, Rodriguez Bouza T, Hsu FI, Sloane DE, Castells MC. results, with Cinfamar Cafeína 10 mg/mL (5×4 mm), Cinfamar Hypersensitivity reactions to mAbs: 105 desensitizations in 23 10 mg/mL (4×4 mm), and theophylline 20 mg/mL. Intradermal patients, from evaluation to treatment. J Allergy Clin Immunol. tests performed with diphenhydramine at dilutions of 5, 0.5, and 0.05 mg/mL were negative. The same tests were also 8. Sanz I. Indications of rituximab in autoimmune diseases. Drug negative in 5 atopic and 5 nonatopic controls. The excipients Discov Today Ther Strateg. 2009;6:13-9.
in Cinfamar Cafeína were also found in other drugs taken by 9. Chung CH. Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist. We performed a single-blind controlled oral challenge test with diphenhydramine. A few minutes after the intake of 12.5 mg of the drug, the patient presented palm and plantar pruritus, dyspnea, pharyngeal occupation, dizziness, ❚ Manuscript received August 2, 2010; accepted for publication, hypotension (65/40 mm Hg), nausea, vomiting, intercostal and abdominal breathing, urinary relaxation, and syncope. She was treated with epinephrine, Actocortina (hydrocortisone sodium O Abadoglu
Cumhuriyet University, Faculty of Medicine phosphate), fl uid therapy, and oxygen in the intensive care unit and recovered completely within a few hours. SPTs with loratadine (5 mg/mL), cetirizine (10 mg/mL), hydroxyzine (5 mg/mL), fexofenadine (12 mg/mL), mizolastine (1 mg/mL), ebastine (10 mg/mL), azelastine (5 mg/mL), and dexchlorpheniramine (5 mg/mL) were negative. Single-blind controlled oral challenges with Anaphylactic Shock Caused by Antihistamines
theophylline, loratadine, and ibuprofen were tolerated. Serum total tryptase levels were normal.
P Mur Gimeno,1 T Alfaya Arias,1 M Iglesias Aranzazu,1 We found no in vitro specifi c immunoglobulin (Ig) E to diphenhydramine using the dot-blot method. The Basotest (a 1Allergy Unit, Hospital Santa Bárbara, Puertollano, Spain kit for the quantitative determination of basophil activation 2R&D Laboratory, ALK-Abelló, Madrid, Spain in human heparinized blood) applied to diphenhydramine 3Immunology Service, IIS-Fundación Jimenez Díaz, Madrid, We believe that the mechanism involved in the anaphylactic shock experienced by our patient might have Key words: Anaphylaxis. Basophil activation test. Diphenhydramine. Histamine antagonists. Dot-blot.
been an IgE-mediated hypersensitivity reaction caused by diphenhydramine. The clinical symptoms and results of the Palabras clave: Anafilaxia. Test de activación de basófilos. SPTs and oral challenge support this hypothesis. The dot-blot Difenhidramina. Antihistamínicos. Inmunoblot.
and Basotest methods failed to demonstrate this mechanism but this is a common problem in drug allergy because drugs can act as haptens or through reactive metabolites likely to haptenate. Barranco et al [1] reported an anaphylactic reaction Antihistamines are widely used drugs which rarely produce to diphenhydramine in a nonatopic patient with a positive immediate hypersensitivity reactions, although contact or intradermal test and challenge but a negative SPT and specifi c photoallergic dermatitis and fi xed drug eruptions have been IgE in vitro tests. Weidinger et al [2], in turn, reported an reported frequently. Dimenhydrinate is an equimolecular anaphylactic reaction to mizolastine in a patient with a positive preparation of 2 drugs, the antihistamine diphenhydramine and 8-chlorotheophylline, a xanthine derivative which reduces Our patient tolerated loratadine, an antihistamine from the the sedating properties of diphenhydramine. The preparation piperidine group, and had a negative SPT to an antihistamine is used to treat dizziness, nausea, anxiety, and cold symptoms.
from a different group to diphenhydramine (ethanolamine), We report the case of a patient with anaphylactic suggesting selective sensitization to diphenhydramine. This shock caused by diphenhydramine and tolerance of other is discordant with the hypothesis of a malfunction of the histamine H1 receptor or nonimmunologic antihistamine A 48-year-old housewife with nasal polyps and perennial intolerance, as has been suggested by other authors in very rhinitis and asthma exacerbated by olive pollen in the spring reported an episode of generalized itchy erythematous lesions We highlight the rapid onset of symptoms and the small J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 dose of antihistamine necessary to trigger the reaction after reexposure, suggesting previous sensitization [4]. Measurements of Fractional Exhaled Nitric
Diphenhydramine is clearly the offending drug, even though in Oxide With 2 Portable Electrochemical Sensors:
vitro tests showed no evidence of the mechanism [5]. An oral A Comparative Study
challenge starting with a lower dose could have diminished the severity of the reaction [6].
JM Olaguíbel,1 A Parra,2 MJ Álvarez,1 S Quirce,3 R López21 The potentially life-threatening adverse event experienced Complejo Hospitalario de Navarra, Pamplona, Spain by this patient should make us aware of the possibility, albeit Complexo Hospitalario Universitario A Coruña, A Coruña, small, of allergic reactions to such widely used drugs as Hospital La Paz, Madrid, Spain Comité de Asma de la Sociedad Española de Alergología e Inmunología clínica Key words: Agreement. Asthma. Fractional exhaled nitric oxide. Acknowledgements
Palabras clave: Acuerdo. Asma. Fracción exhalada de óxido nítrico. We thank Jesus Novalbos, PhD (Generic Clinical Research Manager, Spain) for his pharmaceutical advice and Francisca Prieto Valderrey, PhD (Intensive Care Service, Hospital Santa Bárbara, Puertollano), who provided invaluable clinical assistance.
Fractional exhaled nitric oxide (FENO) is a marker that Previous presentation: This study was presented as a
enables us to measure eosinophilic airway infl ammation. poster at the International Symposium on Drug Hypersensitivity It has potential applications in respiratory allergic diseases organized by the Spanish Society of Allergology and Clinical for diagnosis, selection of therapy, dose adjustment, and Immunology (SEIAC) in Logroño, Spain in October 2009.
assessment of adherence to inhaled corticosteroids [1]. The emergence of new portable devices for clinical practice has simplifi ed and lowered the costs of the measurements. References
Although numerous publications analyze clinical uses of FENO, few studies provide data on whether measurements 1. Barranco P, López-Serrano MC, Moreno-Ancillo A. Anaphylactic performed with different devices authorized for clinical use reaction due to diphenhydramine. Allergy. 1998; 53: 814.
are comparable [2]. The aim of this study was to compare the 2. Weidinger S, Mempel M, Ollert M, Elser I, Rakoski J, Köhn FM, degree of agreement between FENO measurements made with 2 Ring J. Anaphylaxis to mizolastine. J Allergy Clin Immunol. devices frequently used in Europe–the Niox Mino (Aerocrine, Lund, Sweden), which is the reference technique, and the 3. Rodríguez del Río P, González-Gutierrez ML, Sánchez-López J, NO Vario Analyzer (Filt, Berlin, Germany)–both of which Núñez-Acevedo B, Bartolomé Álvarez JM, Martínez-Cócera C. are based on electrochemical sensors. Niox Mino performs Urticaria caused by antihistamines: report of 5 cases. J Investig well in comparison with the more accurate measurements Allergol Clin Immunol. 2009; 19 (4): 317-20.
provided by electrochemiluminescence. Both devices follow 4. Gonzalo-Garijo MA, Jiménez-Ferrera G, Bobadilla-González P, the recommendations of the American Thoracic Society/ Cordobés-Durán C. Hypersensitivity reaction to mizolastine: European Respiratory Society [3]. The measurement range study of cross reactions. J Investig Allergol Clin Immunol. 2006; is 5-300 ppb for the Niox Mino and 2-5000 ppb for the NO Vario, with an accuracy of 3 ppb or <10% for both instruments. 5. Demoly P, Messaad D, Benahmed S, Sahla H, Bousquet J. According to the manufacturers, the accuracy of Niox Mino Hypersensitivity to H1-antihistamines. Allergy. 2000; 55: 679-80.
is ±5 ppb for values <50 ppb, ±10 ppb for values 50-100 ppb, 6. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez and ±25 ppb for values >100 ppb, expressed as the difference J, Brockow K, Pichler WJ, Demoly P for EDNA and the EAACI ±1 SD between a Niox Mino measurement value and the interest group on drug hypersentitivity. Drug provocation corresponding value measured with the NIOX instrument from testing in the diagnosis of drug hypersensitivity reactions: Aerocrine. According to independent investigators, accuracy is general considerations. Allergy. 2003; 58: 854-63.
within the limits set by the manufacturer, although the readings are consistently higher [4,5]. Our study sample comprised 32 adults (15 healthy controls ❚ Manuscript received September 15, 2010; accepted for publication, December 10, 2010. and 17 patients with respiratory allergy) with a mean age of 38 years (range, 17-63). The measurements were made according Pilar Mur Gimeno
to the manufacturers, recommendations and in a random order, with an interval of 2 minutes between readings. In addition to the descriptive statistical analysis and correlation between measurements, we analyzed agreement between the 2 devices The mean (SD) FENO measurement was 21.8 (12.4) ppb for Niox Mino and 22.11 (11.3) ppb for NO Vario; the correlation between the 2 devices was excellent (r=0.971, P<.000). The J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 more evident in subjects with higher concentrations. Allergy. 6. Bland JM, and Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;327:307-10.
❚ Manuscript received October 6, 2010; accepted for publication December 10, 2010. Jose Mª Olaguibel
Hypersensitivity to Pollen Panallergens (Profi lin
and Polcalcin) Detected In Vitro and In Vivo: a
Comparative Analysis
Absolute Difference Between Both Measurements of FE Ambulatorio di Allergologia, Clinica San Carlo, Paderno Figure. Analysis of agreement between the 2 measurements. Key words: Profi lin. Calcium-binding protein. Allergens. Pollen.
Palabras clave: Profi lina. Proteína de unión a calcio. Alérgenos. Polen.
measurements ranged from 6 ppb to 63 ppb. Agreement was excellent between both measurements, with an average difference of –0.30 ppb (range, –7.4 to 6.80), as shown in the Profi lin and polcalcin are plant panallergens. Profi lin can Figure. These differences followed a random distribution and cause cross-reactivity between pollen and vegetable foods [1,2]; polcalcins are cross-reacting pollen allergens [3,4]. We found the degree of agreement between the Polcalcin and profi lin hypersensitivity affects between 10% measurements made with both devices in control subjects to and 30% of pollen-allergic patients [5]; sensitized individuals be excellent. However, this agreement should be verifi ed in react to several botanically unrelated sources. Recombinant asthmatic subjects with higher levels of FE profi lins and polcalcins are now available for routine in vitro diagnosis of allergy, and profi lin- and polcalcin-enriched natural pollen extracts for skin prick tests (SPT) have recently References
been produced. This study compared in vivo and in vitro tests for profi lin and polcalcin.
1. Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett We studied 59 patients (age, 12-72 years) with seasonal D, Comhair SAA, Bleecker E, Busse W, Calhoun WJ, Castro respiratory symptoms and positive SPT results to more M, Chung KF, Israel E, Jarjour N, Moore W, Peters S, Teague than 4 extracts from among the following: grass, mugwort, G, Gaston B, Erzurum SC, for the National Heart Lung, and ragweed, pellitory, plantain, birch, olive (50 000 SBU/mL; Blood Institute Severe Asthma Research P. Use of exhaled nitric Allergopharma, Reinbeck, Germany), Platanus, and cypress oxide measurement to identify a reactive, at-risk phenotype (30 HEP; ALK-Abelló, Madrid, Spain). Fifty-seven and 48 among patients with asthma. Am J Respir Crit Care Med. were assessed for profi lin and polcalcin hypersensitivity, respectively, both by SPT (ALK-Abelló, see below) and in 2. Taylor DR. Exhaled nitric oxide: still alive, not laid to rest. Am J vitro (measuring immunoglobulin [Ig] E to grass profi lin or Respir Crit Care Med. 2009;179:88-9.
3. ATS/ERS Recommendations for standardized procedures for the To prepare profi lin-enriched SPT, Pho d 2 was purifi ed online and offl ine measurement of exhaled lower respiratory from date palm pollen using affi nity chromatography [5]; purity nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care was checked using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE), mass spectrometry, and amino 4. Fortuna AM, Feixas T, and Casan P. [Measurement of fraction of acid analysis. The fi nal concentration of Pho d 2 was adjusted exhaled nitric oxide with the portable NIOX-MINO monitor in to 50 μg/mL. Polcalcin-enriched SPT was obtained from the healthy adults]. Arch Bronconeumol. 2007;43:176-9.
same extract after Pho d 2 purifi cation. Protein identity was 5. Prieto L. Exhaled nitric oxide measurements using a hand-held assessed using SDS-PAGE. The fi nal concentration of polcalcin monitor and a chemiluminescence equipment: difference is was 1 μg/mL by inhibition assay using the ADVIA-Centaur J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 platform (Siemens Healthcare Systems, Madrid, Spain). IgE was extracts, suggesting that SPT+/ImmunoCAP– patients were measured using FEIA ImmunoCAP (Phadia, Uppsala, Sweden); sensitized to 1 of the 2 panallergens. We could speculate that levels greater than 0.35 kUA/L were considered positive. some patients reacted to isoforms other than those present in Altogether, 50/57 (88%) patients were profi lin reactors. the rPhl p 7 and rPhl p 12 used in ImmunoCAP. Furthermore, The results of in vivo and in vitro tests were consistent recombinant profilins from different sources may show signifi cant differences in sensitivity [7]. Table. In Vivo and In Vitro Findings in Patients Showing Discrepancies Between Skin Prick Test and CAP Acknowledgments
The author is particularly grateful to Drs Domingo Barber and Lucia Jimeno (ALK-Abelló R & D, Madrid, Spain) for the gift of profi lin- and polcalcin-enriched date palm pollen extracts, as well as for their technical support.
References
1. Valenta R, Duchene M, Ebner C, Valent P, Sillaber C, Deviller P, Ferreira F, Tejkl M, Edelmann H, Kraft D, Scheiner O. Profi lins constitute a novel family of functional plant pan-allergens. J Abbreviations: Ig, immunoglobulin; SPT, skin prick test.
2. Asero R, Jimeno L, Barber D. Preliminary results of a SPT study about prevalence and clinical relevance of hypersensitivity to bSkin reactivity to purifi ed date palm profi lin and polcalcin is expressed pollen pan-allergens (polcalcin and profi lin). J Invest Allergol as a function of the SPT induced by a positive control (histamine 10 mg/mL): Clin Immunol. (In press). 2010;20:35-8.
0, SPT negative; 2, mean diameter of the wheal al least half that of the 3. Wopfner N, Dissertori O, Ferreira F, Lackner P. Calcium-binding control wheal; 3, equivalent to the diameter of the control wheal; 4, mean proteins and their role in allerrgic diseases. Immunol Allergy diameter of the wheal exceeding that of the control wheal.
4. Tinghino R, Twardosz A, Barletta B, Puggioni EM, Iacovacci in 48/57 (84%) cases: negative in 7 patients and positive in P, Butteroni C, Afferni C, Mari A, Hayek B, Di Felice G, Focke 41 patients. In 9 patients, the results were discordant (Table): M, Westritschnig K, Valenta R, Pini C. Molecular, structural, 7 patients were SPT+/ImmunoCAP–, whereas 2 were and immunologic relationships between different families of SPT–/ImmunoCAP+. Polcalcin hypersensitivity was detected recombinant calcium-binding pollen allergens. J Allergy Clin in 15/48 (31%) patients. The results of in vivo and in vitro tests were consistent in 45/48 patients (94%): negative in 33 cases, 5. Asturias J.A., Ibarrola I, Fernandez J, Arilla MC, Gonzalez-Rioja positive in 12. In 3 patients, the tests produced discordant results R, Martinez A. Pho d 2, a major allergen from date palm pollen, (Table); all 3 were SPT+/ImmunoCAP–. SPT specifi city was is a profi lin: cloning, sequencing, and immunoglobulin E cross- checked by testing with 100 single-pollen reactors (44, grass, 33, reactivity with other profi lins. Clin Exp Allergy. 2005;35:374-81.
ragweed, 16 birch, 4 pellitory, 3 cypress) and 30 patients with 6. Barber D, de la Torre F, Lombardero M, Antepara I, Colas C, chronic urticaria but no respiratory allergy with both extracts; no Dávila I, Tabar AI, Vidal C, Villalba M, Salcedo G, Rodríguez R. positive SPT was recorded. The specifi city of in vitro tests was Component-resolved diagnosis of pollen allergy based on skin checked using sera from 30 single-pollen reactors (10 grass, 10 testing with profi lin, polcalcin, and lipid transfer protein pan- ragweed, 6 birch, 2 cypress, and 2 pellitory); no positive results allergens. Clin Exp Allergy. 2009;39:1764-73.
were recorded. Thus, the sensitivity of SPT and ImmunoCAP 7. Villalta D, Asero R. Sensitization to the pollen panallergen profi lin. Is was, respectively, 96% (48/50) and 86% (43/50) for profi lin and the detection of IgE to multiple homologous proteins from different 100% (15/15) and 80% (12/15) for polcalcin. These differences sources clinically useful? J Invest Allergology Clin Immunol. (In press) were not statistically signifi cant.
This study confi rms that SPT with natural extracts enriched in pollen panallergens are useful diagnostic tools for the allergologist [6]. They are less expensive and time-consuming ❚ Manuscript received June 11, 2011; accepted for publication than in vitro assays and produce results within minutes in the offi ce. When negative, they detect cosensitization to different Riccardo Asero, MD
pollen sources; when positive, they detect corecognition of cross- reacting allergens and prompt in vitro investigations. Although the number of polcalcin reactors (n=15) was too low to draw defi nitive conclusions, it seems that the sensitivity of these SPT may slightly be even superior (though not signifi cantly) to ImmunoCAP; in fact, although reactivity to specifi c date pollen allergens cannot be ruled out, no control patients reacted to the J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 Immediate Type 1 Hypersensitivity to
Apomorphine: A Case Report
D Gutiérrez,1 A Foncubierta,2 R Espinosa,3 S Astorga,1 A Leon,1 S Fernández41UGC Neumología-Alergia, Hospital Universitario Puerta del Mar, Cádiz, Spain2UGC Dr. Joaquin Pece, Distrito Sanitario Bahía de Cádiz-La Janda, Spain3UGC Neurología, Hospital Universitario Puerta del Mar, Cádiz, Spain4UGC Alergología, Hospital Universitario Carlos Haya, Málaga, Spain Key words: Apomorphine. Hypersensitivity. Parkinson disease. Palabras clave: Apomorfi na. Hipersensibilidad. Enfermedad de Parkinson. Figure. Raised wheals on underarms, groin, chest, sacrum, and buttocks.
Injectable apomorphine is commonly used as rescue blind placebo-controlled provocation test with subcutaneous therapy for intractable off periods in Parkinson disease [1]. apomorphine 10 mg/mL produced a positive response after It is administered as an intermittent subcutaneous rescue approximately 20 minutes, with scattered papules measuring injection to reverse drug-refractory off periods and as a 4 to 5 cm in diameter and erythematous lesions on the lower continuous diurnal subcutaneous apomorphine infusion [2], back, buttocks, chest, underarm, and penis, which disappeared which typically provides a clinical benefi t within 10 minutes [1] 30 minutes later. As the commercial preparation of apomorphine A 56-year-old man experienced episodes of raised itchy contains 0.093% sodium bisulphite, a known trigger for contact wheals on the underarms, groin, chest, lower back, and dermatitis, our patient underwent a double-blind placebo- buttocks approximately 20-25 minutes after subcutaneous controlled trial with sodium metabisulphite in 50 mg, 100 mg, administration of 4-6 mg apomorphine (Figure). The symptoms and 150 mg doses; the results were negative. Our fi ndings for disappeared 30 minutes later with no residual lesions when the total immunoglobulin (Ig) E and specifi c IgE values (Hytec, effects of the drug had worn off. The patient showed no clinical Hycor Biomedical Ltd, Penicuik, UK) were not signifi cant.
signs of mastocytosis, either as a result of massive release of Adverse skin reactions to apomorphine have been described mast cell mediators following chronic release of mast cells or in less than 1% of patients [3]. Sodium metabisulphite has been as a result of tissue infi ltration. He had no history of idiopathic identifi ed as a cause of contact dermatitis [4] and of allergic or nonsteroidal anti-inflammatory drug (NSAID)–related reactions. In our study, SPTs with aeroallergens and the sodium anaphylactic reactions or life-threatening vascular collapse, metabisulphite provocation test produced negative responses. and NSAIDs (eg, ibuprofen, aspirin) to treat a herniated disc The positive response by our patient to the single-blind placebo- were well tolerated. Apart from the medication prescribed controlled provocation test with apomorphine 10 mg/mL suggests for Parkinson disease and occasional NSAIDs (metamizole), an IgE-mediated mechanism that we are unable to contrast with all of which he tolerated well, the patient was taking no others due to the paucity of related studies in the literature. To antihypertensive medication (angiotensin-converting enzyme our knowledge, this is the fi rst report of a type I hypersensitivity inhibitors, ß-blockers, or angiotensin receptor blockers). On one occasion he was prescribed tramadol. Although ingestion of morphine and opioid derivatives can produce nonspecifi c release of mast cell mediators, no such release of histamine References
occurred in our patient following ingestion of tramadol. Skin prick test (SPT) responses were negative with aeroallergens Factor SA. Literature review: intermittent subcutaneous and foods. SPT with apomorphine 10 mg/mL and intradermal apomorphine therapy in Parkinson’s disease. Neurology. tests with diluted apomorphine at concentrations of 1:1000 and 1:100 were also negative. An intradermal test at a dilution of 2. Poewe W, Wenning GK. Apomorphine: an underutilized therapy for 1:10 resulted in a 6-mm papule in our patient and a negative Parkinson’s Disease. Movement Disorders. 2000;15(5):789-94.
response in 14 control subjects. Patch testing on our patient 3. Deleu D, Hanssens Y, Northway MG. Subcutaneous apomorphine: with apomorphine 10 mg/mL diluted in water to 0%, 0.05%, an evidence-based review of its use in Parkinson’s disease. and 1% was negative at 48 hours and 96 hours. A single- J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 4. Acland KM, Churchyard A, Fletcher C, Turner K, Lees A, Dowd Table. Results of Skin Test and Specifi c Immunoglobulin E Determinations PM. Panniculitis in association with apomorphine infusion. Br J ❚ Manuscript received October 17, 2010; accepted for publication Diego Gutiérrez Fernández
Identifi cation of Allergens in Chicken Meat
E González-Mancebo,1 C Pastor,2 D González-de-Olano,1 M Gandolfo-Cano,1 A Melendez,1 J Cuesta,3 A Zapatero,4 1Unidad Alergia, Hospital de Fuenlabrada, Madrid, Spain 2Departmento de Inmunología, Fundación Jiménez Díaz, Madrid, Spain3Departmento de Alergia, Fundación Jiménez Díaz, Madrid, Abbreviations: Ig, immunoglobulin; NP, not performed; SPT, skin prick test.
4Departamento de Medicina Interna, Hospital de Fuenlabrada, Madrid, Spain sIgE determinations against the poultry meat extracts prepared (EAST technique) are shown in the Table. The patient declined Key words: Allergy. Chicken meat. MLC. Myosin. Parvalbumin.
an oral challenge test with duck, quail, and ostrich. Palabras clave: Alergia. Carne de pollo. CLM. Miosina. Potential allergenic components of all these extracts were detected by IgE-immunodetection after separation using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) [5]. SDS-PAGE IgE immunoblotting assays were carried out and revealed reactivity to bands of 16 and 27 kDa in Chicken meat is widely consumed. Most cases of chicken boiled chicken extract, 16 and 28 kDa in boiled duck extract, meat allergy are associated with hypersensitivity to egg and/ and 16 kDa in boiled turkey extract (data not shown). Complete or feather, thus prompting the so-called bird–egg syndrome, inhibition of the IgE-binding bands in boiled extracts of duck with α-livetin (Gal d 5) as the most frequent cross-reacting and turkey was observed when these were preincubated with protein [1]. Few cases of chicken meat allergy without egg boiled chicken extract (data not shown). To identify these IgE- hypersensitivity have been published, and its profile of binding proteins, the 16- and 27-kDa bands from the boiled allergen sensitization has seldom been investigated [2,3], chicken extract were manually excised, digested with trypsin, although α-parvalbumin was recently identifi ed as the allergen and analyzed by mass spectrometry in tandem (MS/MS) [5]. implicated in a case of poultry meat allergy [4]. Proteins were identifi ed using a nonredundant protein sequence A 20-year-old man experienced oropharyngeal and palmar database (National Center for Biotechnology Information). itching, facial hives, lip swelling, dysphagia, dyspnea, and The analysis of the resulting peptides by mass spectrometry heartburn 15 minutes after eating chicken. He tolerated turkey, or MS/MS identifi ed the 16-kDa band as α-parvalbumin and but did not eat any other poultry meat or meats such as veal, the 27-kDa band as myosin light chain 1 (MLC). pork, and rabbit. He tolerated eggs and had no contact with birds. α-Parvalbumin is abundant in the muscle of fi sh and Skin prick tests (SPT) to commercial meat extracts, egg amphibians, rather less so in birds and mammals, and is proteins, and a feather mix extract were performed. Prick-by- not generally described as allergenic, except for a case of prick tests were also carried out with raw and boiled poultry allergy to frog meat [6] and a case of allergy to poultry meat meats (Table). Protein extracts from raw and boiled chicken, [4]. ß-Parvalbumin, which does not usually cross-react with turkey, duck, quail, and ostrich meat were prepared following a α-parvalbumin [7], has been described as a major allergen standard protocol (homogenization in phosphate-buffer-saline, and as the most important allergen in many fi sh species. dialyzation, and lyophilization) and administered as SPTs Parvalbumins are believed to be potent food allergens due to (Table). The results of serum specifi c immunoglobulin (Ig) E their thermal stability and resistance to digestion [7]. Myosins against the commercial meat extracts (Phadia CAPsystem) and are a large superfamily of motor proteins that move along J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 actin fi laments while hydrolyzing adenosine triphosphate. Two light chains of muscle myosin, each measuring 20 kDa, Effect of Alcohol Consumption and Cessation on
wrap around the neck region of the 2 myosin heavy chains [8]. Serum Total Immunoglobulin E Concentrations
Although shrimp MLC (Lit v 3) has been identifi ed as a new major shrimp allergen [8], MLC has never been described as V Coutinho,1 C Vidal,2 L Vizcaino,3 A Gonzalez-Quintela41 Cooperativa de Ensino Superior, Politécnico e Universitário, We present a patient with IgE-mediated allergy to chicken meat and no sensitization to egg proteins. α-Parvalbumin and Department of Allergy, Complejo Hospitalario Universitario, myosin were identifi ed as the relevant allergens. IgE binding to these proteins has also been identifi ed in turkey and duck Department of Biochemistry, Complejo Hospitalario meat. This is the fi rst report of MLC as a potential allergen in Universitario, Santiago de Compostela, Spain4 Department of Internal Medicine, Complejo Hospitalario Universitario, Santiago de Compostela, Spain References
1. Quirce S, Maranon F, Umpierrez A, de las Heras M, Fernandez- Caldas E, Sastre J. Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome. Allergy. 2001;56:754-62.
2. Liccardi G, Szepfalusi Z, Noschese P, Nentwich I, D’Amato M, Alcohol consumption infl uences many aspects of immunity D’Amato G. Allergy to chicken meat without sensitization to egg [1], including a shift towards type 2 helper T cell (TH2) proteins - a case report. J Allergy Clin Immunol. 1997;100:577-9.
responses [1,2]. Observational evidence in humans indicates 3. Cahen YD, Frisch R, Wüthrich B. Food allergy with monovalent that alcohol consumption, particularly heavy consumption, sensitivity to poultry meat. Clin Exp Allergy. 1998;28:1026-30.
is associated with increased serum total immunoglobulin 4. Kuehn A, Lehners C, Hilger C, Hentges F. Food allergy to chicken (Ig) E concentrations [3,4]. However, confounding factors meat with IgE reactivity to muscle α-parvalbumin. Allergy. hamper the inference of causation in observational studies. Alcohol consumption is associated with a number of factors 5. Pastor C, Cuesta-Herranz J, Cases B, Pérez-Gordo M, Figueredo (age, gender, smoking, nutrition, infection, and liver disease) E, de las Heras M, Vivanco F. Identifi cation of major allergens in that affect IgE concentrations. Although the effect of alcohol watermelon. Int Arch Allergy Immunol. 2009;149:289-90.
seems independent of these factors [4], additional uncontrolled 6. Hilger C, Grigioni F, Thill L, Mertens L, Hentges F. Severe IgE- confounders may exist. Temporal ambiguity is a drawback of mediated anaphylaxis following consumption of fried frog cross-sectional studies showing an association between alcohol legs: defi nition of alpha-parvalbumin as the allergen in cause. consumption and serum IgE [4]. Additional evidence for causality includes the reversibility of the effect if the potential 7. Jenkins JA, Breiteneder H, Clare Mills EN. Evolutionary distance cause is removed. The present study investigated the effect of from human homologs refl ects allergenicity of animal food alcohol consumption and the short-term effect of cessation of proteins. J Allergy Clin Immunol. 2007;120:1399-405.
consumption on serum total IgE concentrations.
8. Ayuso R, Grishina G, Bardina L, Carrillo T, Blanco C, Ibáñez MD, The cohort comprised 270 individuals (age, 27-83 years; Sampson HA, Beyer K. Myosin light chain is a novel shrimp 64% men) attending a thermal spa in northern Portugal that is allergen, Lit v 3. J Allergy Clin Immunol. 2008;122:795-802.
offi cially recognized as complementary therapy for hepatobiliary and metabolic diseases [5]. During a standard 14-day stay, individuals follow a supervised diet, drink local mineral waters, and voluntarily abstain from alcohol consumption. Blood samples were provided by all participants on admission and by 211 individuals at the end of the stay. Alcohol consumption was recorded as the number of standard drinking units consumed weekly (glasses of wine, beers, and spirits, each containing about ❚ Manuscript received September 1, 2010; accepted for publication 10 g of alcohol). Occasional alcohol consumers (<1 unit/week) and abstainers were grouped together; regular alcohol consumers Eloína González-Mancebo
were classifi ed as light-to-moderate drinkers (1-28 units/week) or heavy drinkers (>28 units/week) and were grouped separately. Determinations included serum total IgE (Immulite, Siemens, UK) and γ-glutamyltransferase (GGT, Olympus Analyzer, Olympus, Germany), a marker of alcohol consumption. Written consent was obtained from all participants. Serum IgE concentrations were higher in heavy and light- to-moderate drinkers than in occasional drinkers/abstainers (P=.01 and P<.001, respectively; Mann-Whitney test) J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 Figure. Upper panels, Baseline serum concentrations of serum total IgE and GGT in relation to alcohol consumption. Bars represent the interquartile range; horizontal lines represent the median. Lower panels, Mean change in serum concentration of IgE and GGT after 14 days’ cessation of alcohol consumption in the corresponding groups. P values were obtained after comparison of the 3 groups using the Jonckheere-Terpstra test for trend. GGT indicates γ-glutamyltransferase; Ig, immunoglobulin.
(Figure). Multivariate analysis (linear regression) revealed alcohol the association between alcohol consumption and high IgE consumption (in units/week) to be positively associated with IgE levels has biological plausibility. Alcohol consumption induces concentrations after adjusting for age, gender, and smoking (P=.001, changes in cytokine balance with increased production of data not shown). Serum IgE concentrations tended to decrease after TH2 cytokines, which correlates with elevated IgE levels in 14 days in parallel with baseline alcohol consumption (Figure). The alcoholics [4] and in animal models [2]. Some of these effects decrease in serum IgE after cessation of alcohol consumption was could be mediated by intestinal absorption of endotoxin [7]. statistically signifi cant in light-to-moderate drinkers and in heavy For unknown reasons, drinkers are specifi cally at risk of drinkers (P<.001 in both cases, Wilcoxon test). Variations in serum sensitization to cross-reactive carbohydrates [8,9].
IgE paralleled those of serum GGT (Figure). In summary, regular alcohol consumption (even light-to- These results support the notion that alcohol consumption moderate drinking) is associated with increased serum total increases serum total IgE levels. According to the classic IgE concentrations, which tend to normalize shortly after criteria for causality, there is experimental evidence in animals abstinence. Alcohol consumption should be considered when [2], consistency among studies, strength of association, a dose- response effect, independence of confounders [4], and a trend toward reversal shortly after elimination of the cause, as shown here. The short half-life of serum IgE [6] allows changes to be Acknowledgments
observed over a short period. A similar trend has been reported in small samples of alcoholics admitted to the hospital [3,4], The study was supported by a grant from the Instituto de but not in drinkers from the general population. Furthermore, Salud Carlos III (Spanish Ministry of Health, PI10/01870).
J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329 References
alcohol consumption on serum IgE levels. Alcohol Clin Exp Res. 2006;30:7-14.
1. Szabo G. Consequences of alcohol consumption on host 8. González-Quintela A, Garrido M, Gude F, Campos J, Linneberg defence. Alcohol Alcohol. 1999;34:830-41.
A, Lojo S, Vidal C. Sensitization to cross-reactive carbohydrate 2. Heinz R, Waltenbaugh C. Ethanol consumption modifi es determinants in relation to alcohol consumption. Clin Exp dendritic cell antigen presentation in mice. Alcohol Clin Exp 9. González-Quintela A, Garrido M, Gude F, Campos J, Lojo S, 3. Hallgren R, Lundin L. Increased total serum IgE in alcoholics. Linneberg A, Vidal C. Discordant positive results of multiallergen immunoglobulin E tests in relation to crossreactive carbohydrate 4. Gonzalez-Quintela A, Vidal C, Gude F. Alcohol, IgE and allergy. determinants and alcohol consumption. J Investig Allergol Clin 5. Coutinho V, Vidal C, Garrido M, Gude F, Lojo S, Linneberg A, González-Quintela A. Interference of cross-reactive carbohydrates in the determination of specifi c IgE in alcohol drinkers and strategies to minimize it: the example of latex. Ann ❚ Manuscript received January 15, 2011; accepted for publication Allergy Asthma Immunol. 2008;101:394-401.
6. Hamilton RG. Clinical laboratory assessment of immediate-type Dr A González-Quintela
hypersensitivity. J Allergy Clin Immunol. 2010;125:S284-96.
7. Campos J, Gude F, Quinteiro C, Vidal C, González-Quintela A. Gene by environment interaction: the -159C/T polymorphism in the promoter region of the CD14 gene modifi es the effect of J Investig Allergol Clin Immunol 2011; Vol. 21(4): 317-329

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