Short Communications and Brief Case Notes SHORT COMMUNICATIONS AND BRIEF CASE NOTES that the determination of specifi c IgE, and especially IgG, to Fatal Intraoperative Anaphylaxis After
aprotinin should be evaluated in patients with prior contact Aprotinin Administration
with this peptide. Patients with high antibody titers should be considered at risk, whereas the absence of aprotinin-specifi c IgG has been reported to indicate low risk of a hypersensitivity Allergology Service, Hospital General Universitario Gregorio reaction [1-3]. Recently, the Spanish Drug Agency has issued an offi cial bulletin recommending that IgG specifi c antibodies be determined prior to aprotinin administration. They also stress Key words: Anaphylaxis. Aprotinin. Aprotinin-specific that aprotinin administration is contraindicated in patients in immunoglobulin G and E antibodies. Tryptase.
whom specifi c-IgG antibodies are detected as well as in patients Palabras clave: Anafi laxia. Aprotinina. Anticuerpos específi cos possibly exposed to aprotinin within the last 12 months. frente a aprotinina inmunoglobulina G e E. Triptasa. Recent publications indicate that the use of aprotinin is associated with a dose-dependent higher risk of renal failure and multiorgan damage, including heart and brain injury. The risk of long-term Aprotinin is a 6512-dalton bovine peptide antifi brinolytic mortality is also higher after the use of aprotinin in comparison with agent. Due to its inhibitory effect on proteolytic enzymes the use of lysine analogs aminocaproic acid and tranexamic acid. It has (trypsin, plasmin, kallikrein), it is used to reduce blood therefore been suggested to use those safer and cheaper alternatives loss and transfusion requirements and to limit the systemic and to withdraw aprotinin from human use [4-6]. infl ammatory response in major surgery under extracorporeal circulation (cardiac surgery, lung and liver transplantation, hip replacement). The frequency of allergic reactions to aprotinin References
has been estimated at 2.8 % when patients are re-exposed to this peptide within a 6-month period [1, 2].
1. Beierlein W, Scheule AM, Dietrich W, Ziemer G. Forty years of We present the case of a 76-year-old man with no history of clinical aprotinin use: a review of 124 hypersensitivity reactions. previous allergic diseases who underwent aortic valve replacement due to prosthetic valve endocarditis. Remifentanil, fentanyl, 2. Dietrich W, Späth P, Zühlsdorf M, Dalichau H, Kirchhoff PG, Kuppe H, etomidate, midazolam, atracurium, and cefazolin were given Preiss DU, Mayer G. Anaphylactic reactions to aprotinin reexposure during anesthesia. Sixty minutes after induction, intravenous in cardiac surgery: relation to antiaprotinin immunoglobulin G and aprotinin (Trasylol, Bayer AG, Levercusen, Germany) was E antibodies. Anesthesiology. 2001;95:64-71.
administered; it induced immediate hypotension, pulmonary 3. Scheule AM, Beierlein W, Arnold S, Eckstein FS, Albes JM, Ziemer G. hypertension, ventricular fi brillation and cardiorespiratory arrest. The signifi cance of preformed aprotinin-specifi c antibodies in The patient died after 2 hours of advanced cardiopulmonary cardiosurgical patients. Anesth Analg. 2000;90:262-6.
resuscitation. When aprotinin had been administered intravenously 4. Mangano DT, Tudor IC, Dietzel C, Multicenter Study of 2 months earlier, tolerance had been good.
Perioperative Ischemia Research Group, Ischemia Research and Serum tryptase levels measured 167 ␮g/L and 3.8 ␮g/L Education Foundation. The risk associated with aprotinin in (CAP Pharmacia, Uppsala, Sweden ) at the time of the adverse cardiac surgery. N Engl J Med. 2006;354:353-65. reaction and 1 day before surgery, respectively. A peroxidase- 5. Mangano DT, Miao Y, Vuylsteke A, Tudor IC, Juneja R, based enzyme-linked immunosorbent assay demonstrated the Filipescu D, Hoeft A, Fontes ML, Hillel Z, Ott E, Titov T, Dietzel C, presence of specifi c immunoglobulin (Ig) E to aprotinin in Levin J, Multicenter Study of Perioperative Ischemia Research serum. The absorbance measured at 495 nm was 0.728 optical Group, Ischemia Research and Education Foundation. Mortality density (OD) in contrast with 0.090 OD for the mean of the associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA. 2007;297:471-9.
This is a case of fatal anaphylaxis due to aprotinin demonstrated 6. Sodha NR, Boodhwani M, Sellke FW. Is there still a role for by the presence of serum specifi c IgE. Serum tryptase measurement aprotinin in cardiac surgery? Drug Saf. 2007;30:731-40. was essential for the diagnosis of anaphylaxis.
It has been recommended to avoid re-exposure to aprotinin ❚ Manuscript received September 25, 2007; accepted for publication for at least 6 months, since it has been proven to be a main risk factor for anaphylactic reactions [1-3]. Re-exposure to aprotinin within a 2-month period may have been a determinant Alicia Prieto García
Standardized enzyme immunoassay kits are commercially Hospital General Universitario Gregorio Marañón available for the quantitative determination of antiaprotinin IgG antibodies (CellTrend, Luckenwalde, Germany). We propose J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142 Short Communications and Brief Case Notes Use of the Comet Test to Assess DNA Damage in
Children With Ataxia-Telangiectasia and Their

L Moreno Galarraga,1 JL Santos Pérez,1 MC Ramirez-Tortosa,2 JL Quiles Morales,2 S Granados Principal,2 E Martínez de Victoria Muñoz,2 L Ortega Martos11 Department of Pediatrics, University Hospital Virgen de las Nieves, Granada, Spain 2Nutrition and Food Technology Institute, Granada University, Granada, Spain Key words: Ataxia-telangiectasia. DNA damage. Cancer risk. Comet test.
Palabras clave: Ataxia-telangiectasia. Daño en el ADN. Riesgo de cáncer. Prueba cometa.
Figure. Fluorescent microscope images of the different types of cell damage. Damage ranges from type 0 (no damage) to type 4 (maximum Ataxia-telangiectasia is a hereditary autosomal recessive damage). Sample 1, nuclei of lymphocytes from a patient with DNA damage; sample 2, nuclei from a healthy control individual.
disease characterized by immune defi ciency and an increased incidence of tumors. The mutated gene responsible for the disease has been identifi ed. It is known as ataxia-telangiectasia mutated (ATM) and is located on the long arm of chromosome had developed acute lymphoblastic leukemia. That patient had 11 (11q22-23). This gene controls the production of an enzyme a visual score of 233, an olive tail moment of 0.44, and 23% involved in cell responses and the control and repair of the cell cycle [1]. In healthy carriers of ATM, an increased risk The 3 family members studied also had increased values for of cancer has been noted that seems to be related to greater DNA fragmentation. These values were higher than the mean chromosomal instability, and it has been suggested that the found in the healthy controls, but lower than those in patients identifi cation of these heterozygotes would make it possible to with ataxia-telangiectasia (P < .05). DNA fragmentation was include them in cancer screening programs and would permit higher in the group of family members than in the control use of more appropriate cytostatic treatments of cancer [2].
group, in terms of the visual score (36 [10.2]), olive tail Chromosomal instability and cell damage can be estimated moment (0.26 [0.3]), and percentage of DNA in the tail using various techniques [3,4]. In this study, we used the comet test to assess DNA damage in lymphocytes from children with Genetic diagnosis in ataxia-telangiectasia is performed ataxia-telangiectasia, and to measure chromosomal instability by sequencing of the ATM gene [5]. It has been reported that within the family. Seventeen subjects were studied: 4 patients healthy carriers of the ATM gene have an increased risk of diagnosed with ataxia-telangiectasia, 3 family members, and chromosomal instability and higher incidence of tumors [2]. 10 healthy children. Blood samples were obtained by venous We used the comet test to show that patients with ataxia- puncture and lymphocytes were obtained by standard methods. telangiectasia have a higher rate of DNA damage than healthy The cells were embedded in agarose on microscope slides controls. This chromosomal instability is related to the clinical and placed in an electrophoresis tank with an alkaline buffer manifestations in these patients. Our study demonstrates that to allow separation of the DNA chains. Once electrophoresis relatives of patients with ataxia-telangiectasia have higher was complete, the slides were stained with 4’,6-diamidino-2- levels of DNA damage than healthy controls, a fi nding that phenylindole (DAPI). The DAPI-stained nuclei in each gel is consistent with the higher incidence of tumors in such were examined by UV microscopy using Komet 5.1 imaging individuals [6]. Identifi cation of these healthy heterozygotes software (Kinetic Imaging Ltd, Liverpool, UK). The following with the comet test would make it possible to detect patients data were obtained: visual appearance of DNA (Figure), olive at high risk of cancer and would permit modifi cation of the tail moment (product of tail length and fl uorescence intensity), and the percentage of DNA in the tail. Statistics were performed We conclude that electrophoresis of cells in alkaline with SPSS version 13.0. The Kruskall-Wallis test was used to medium (comet assay) is a valid technique for quantifying DNA damage in patients with ataxia-telangiectasia and their The mean (SD) number of DNA fragments assessed visually was higher in patients (131.5 [0.2]) than in controls (15 [9.6]), and the difference was statistically signifi cant (P < .05). The same was true for the olive tail moment values (0.31 [0.5] vs References
0.16 [0.2]) and the percentage of DNA in the tail (17% [6%] vs 10% [5%]). The highest values for chromosome instability 1. Nyati MK, Feng FY, Maheshwari D, Varambally S, Zielske SP, Ahsan were obtained from a patient with ataxia-telangiectasia who A, Chun PY, Arora VA, Davis MA, Jung, M, Ljungman M., Canman, J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142 Short Communications and Brief Case Notes CE, Chinnaiyan AM, Lawrence TS. Ataxia telangiectasia mutated reactions to metronidazole are rarely described. We report a down-regulates phospho-extracellular signal-regulated kinase case of anaphylaxis to metronidazole.
1/2 via activation of MKP-1 in response to radiation. Cancer A 51-year old woman with no history of allergy was referred to our service for evaluation of a drug reaction. She had been 2. Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman treated with spiramycin and metronidazole (Rhodogil, Sanofi - A, Byrd P, Taylor M, Easton DF. Cancer risks and mortality in Aventis, Paris, France) for gingivostomatitis 6 months earlier. heterozygous ATM mutation carriers. J Natl Cancer Inst. Thirty minutes after the fi rst dose in the reported episode, she presented sneezing, rhinorrhea, perioral paresthesia, and 3. Gedik CM, Boyle SP, Wood SG, Vaughan NJ, Collins AR. upper airway angioedema followed by generalized pruritic Oxidative stress in humans: validation of biomarkers of DNA erythematous lesions. The symptoms disappeared within a few hours of administration of corticosteroids and antihistamines. 4. Faust F, Kassie F, Knasmuller S, Boedecker RH, Mann M, Mersch- She remembered a previous episode of labial angioedema Sundermann V. The use of the alkaline comet assay with and sneezing 2 hours after the fi rst dose of Rhodogil. She had lymphocytes in human biomonitoring studies. Mutat Res. 2004; Skin prick tests were performed with erythromycin 5. Mancebo E, Pacho A, de Pablos P, Muñoz-Robles J, Castro MJ, Romo (250 mg/mL), spiramycin (250 mg/mL) and metronidazole E, Morales P, Gonzáles L, Paz-Artal E, Allende L. Rapid molecular (125 mg/mL) with a positive result for metronidazole on diagnosis of ataxia-telangiectasia by optimised RT-PCR and direct 2 different occasions. Skin prick tests with metronidazole sequencing analysis. Immunobiology. 2005;210:279-82.
were negative in 10 controls. An oral provocation test with 6. Smith TR, Miller MS, Lohman KK, Case LD, Hu JJ. DNA damage spiramycin (500 mg) was negative. We also performed and breast cancer risk. Carcinogenesis. 2003;24:883-9. skin prick tests with other imidazole derivatives such us 7. Bernstein JL, Seminara D, Borresen-Dale AL. Workshop on The ketoconazole (20 mg/mL), fluconazole (200 mg/mL), epidemiology of the ATM Gene: Impact on breast cancer risk etomidate (2 mg/mL), mebendazole (100 mg/mL), cimetidine and treatment, present status and future focus, Lillehammer, (200 mg/mL), famotidine (20 mg/mL), ranitidine (150 mg/ Norway, 29 June 2002.Breast Cancer Res. 2002;4:249-52.
mL), ornidazole (500 mg/mL), tiabendazole (500 mg/mL) with negative results. The patient refused oral provocation ❚ Manuscript received September 10, 2007; accepted for publication with metronidazole or derivatives. The positive skin prick test and clinical history strongly suggested anaphylaxis due to metronidazole. To the best of our knowledge, there are no Juan Luis Santos Pérez
previous reports of metronidazole anaphylaxis.
Hospital Universitario Virgen de las Nieves Reports of hypersensitivity reactions to metronidazole that we have located have mentioned fi xed exanthems [1,2]; irritation, pruritus and burning with topical metronidazole [3]; exanthems varying from pityriasis rosea and acute pustulosis to toxic epidermal necrolysis [4,5]; cutaneous exanthems (2 immediate and 2 delayed) [6]; and rhinoconjunctivitis (1 case) and asthma crisis (1 case) [7]. Anaphylaxis Due to Metronidazole With Positive
In general, the sensitivity of skin tests is low. Thus, Skin Prick Test
epicutaneous tests have been positive at different concentrations on residual lesions in some cases of fi xed exanthems [1,2,7], T Asensio, I Dávila, E Moreno, E Laffond, E Macías, A Ruiz, and skin prick tests with metronidazole have usually been negative [6-8]. We have only found 1 report of a patient with Department of Allergy, University Hospital of Salamanca, a positive skin prick test that suffered from angioedema and micropapular exanthems on the face, neck and thighs after 4 doses of Rhodogil [6]. Cross-reactions have been reported Key words: Anaphylaxis. Metronidazole. Prick test. Cross-reactivity. between metronidazole and tinidazole [9] and between albendazole and metronidazole by oral challenge testing [10]. Palabras clave: Anafilaxia. Metronidazol. Prueba cutanea. Others have found a lack of reactivity between metronidazole, Reactividad cruzada. Derivados imidazólicos.
tinidazole, tioconazole, albendazole, ketoconazole, and mebendazole by patch testing [8,11]. Generally, only the drug involved in the reaction has been evaluated in clinical studies; Metronidazole is a drug belonging to the 5-nitroimidazole Therefore, studies with compounds from all the imidazole series group. It shares a high structural similarity with its derivatives would be useful in order to evaluate their cross-reactivity. Our (tinidazole, secnidazole, and ornidazole). It is used to treat patient refused oral challenge and, due to the severity of the trichomonas vaginalis, amebiasis, and anaerobic infections reaction and because other therapeutic alternatives are available, in combination with other antibiotics. The drug is usually we recommended avoiding all the imidazoles.
well involve tolerated; the most common side effects involve In conclusion, this case of anaphylaxis to metronidazole gastrointestinal symptoms, reversible hematological alterations, was supported by a positive skin prick test suggesting an and disorders of the central nervous system. Hypersensitivity J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142 Short Communications and Brief Case Notes References
Short-acting ß -agonists are the fi rst-line drugs for treating reversible airway obstruction, such as in asthma and in certain 1. Short KA, Fuller LC, Salisbury JR. Fixed drug eruption following patients with chronic obstructive pulmonary disease. Adverse metronidazole therapy and the use of topical provocation effects or bronchoconstriction after their use have been testing in diagnosis. Clin Exp Dermatol. 2002;27(6):464-6.
documented [1], but to our knowledge no cases of anaphylactic 2. Gastaminza G, Anda M, Audicana MT, Fernández E, Muñoz D. Fixed drug eruption due to metronidazole with positive topical A 42-year-old woman diagnosed with asthma due to pollen provocation. Contact Dermatitis. 2001;44(1):54-55.
was treated with nebulized salbutamol and budesonide after 3. Colón LE, Johnson LA, Gottschalk RW. Cumulative irritation an acute exacerbation. Ten minutes later, she experienced potential among metronidazole gel 0.75%, and azelaic acid generalized itching and erythema, eyelid swelling, chest tightness, nausea, and abdominal pain. She had previously 4. Chen KT, Twu SJ, Chang HJ, Lin RS. Outbreak of Steven- Johnson syndrome/toxic epidermal necrolysis associated with Skin prick tests and intradermal tests with salbutamol and mebendazole and metronidazole use among Filipino laborers budesonide were negative. The patient signed an informed in Taiwan. Am J Public Health. 2003;93(3):489-92.
consent statement for drug challenge and was then administered Knowles S, Choudhury T, Shear NH. Metronidazole 200 ␮g and 400 ␮g of inhaled budesonide at an interval of 1 hypersensitivity. Ann Pharmacother. 1994;28(3):325-6.
hour. Tolerance was good. She was later administered 100 ␮g 6. García-Rubio I, Martínez-Cócera C, Santos Macadán S, and 200 ␮g of inhaled salbutamol. After the second dose, Rodríguez-Jiménez B, Vázquez-Cortés S. Hypersensitivity she experienced 10 minutes of facial itching that resolved reactions to metronidazole. Allergol Immunopathol (Madr). spontaneously. Afterwards, we decided to challenge with nebulized salbutamol together with budesonide. Five minutes 7. Aníbarro B, Fontela JL. Immediate rhinoconjunctivitis induced by after the administration, she began feeling generalized itching metamizole and metronidazole. Ann Allergy Asthma Immunol. and erythema, eyelid swelling, chest tightness and abdominal pain. A skin prick test to latex was negative and the specifi c 8. Prieto A, de Barrio M, Infante S, Torres A, Rubio M, Olalde S. serum immunoglobulin E (IgE) titer was less than 0.35 kU/L. Recurrent fi xed drug eruption due to metronidazole elicited by The patient was then separately challenged with inhaled match test with tinidazole. Contact Dermatitis. 2005;53:169-170.
placebo, nebulized saline solution, and nebulized budesonide, 9. Mahboob A, Haroon Ts. Fixed drug eruption with albendazole with good tolerance. After the challenge with nebulized and its cross-sensitivity with metronidazole: a case report. J Pak salbutamol, she again experienced generalized itching and erythema, eyelid and palmar swelling, chest tightness, nausea 10. Thami GP, Kanwar AJ. Fixed drug eruption due to metronidazole and abdominal pain (Figure). A basophil activation test (BAT) and tinidazole without cross-sensitivity to secnidazole. to salbutamol was performed next, but no activation was detected with concentrations of 0.39 ␮g/mL, 1.56 ␮g/mL, 6.25 ␮g/mL or 25 ␮g/mL. An anti-IgE activation carried out prior the BAT to salbutamol was negative as well. Patch tests ❚ Manuscript received October 24, 2007; accepted for publication November 30, 2007. Teresa Asensio Sánchez
Anaphylaxis to Salbutamol
D González de Olano,1 MJ Trujillo Trujillo,1 S Santos- Magadán,1 A Menéndez -Baltanás,1 M Gandolfo Cano,1 S Ariz Muñoz,2 ML Sanz Larruga,2 E. González-Mancebo11 Allergy Unit, Hospital de Fuenlabrada, Madrid, Spain2 Department of Allergy and Clinical Immunology, University Clinic of Navarra, Pamplona, Spain Key words: Anaphylaxis. Basophil activation test. Short-acting ß - Palabras clave: Anafi laxis. Beta-2-agonistas de acción corta. Figure. Generalized erythema and eyelid and palmar swelling after Prueba de activación de basófi los. Salbutamol J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142 Short Communications and Brief Case Notes with salbutamol and terbutaline were also negative. We decided 8. de Weck AL, Sanz ML, Gamboa PM, Aberer W, Bienvenu J, not to challenge with any other short-acting ß -agonists. Blanca M, Demoly P, Ebo DG, Mayorga L, Monneret G, Sainte Tolerance was good to further challenges with long-acting Laudy J. Diagnostic tests based on human basophils: more ß - agonists (formoterol and salmeterol). potential and perspectives than pitfalls. I. Clinical Studies. Int Salbutamol is an adrenergic agonist bronchodilator with a higher affi nity for ß -receptors. In the airway, activation of ß -receptors results in relaxation of bronchial smooth muscle and a widening of the airway. Its onset of action is rapid, ❚ Manuscript received November 7, 2007; accepted for publication November 21, 2007. providing relief within 5 to 15 minutes of administration.
Short-acting ß -agonists are widely used and side effects David González de Olano
like tremor, palpitations and headache are commonly described [1]. So-called paradoxical bronchoconstriction to salbutamol has also been documented [2-4]. In a recently reported case of severe bronchoconstriction with different short acting ß -agonists, an IgE-mediated mechanism was suspected and tolerance to long-acting ß -agonists was good [5].
In the case we report, the immunological mechanism involved in the reaction remains unclear. BAT is based on the detection Allergy to Proton Pump Inhibitors: Diagnosis
of allergen-induced CD63 expression on basophils (a marker and Assessment of Cross-Reactivity
of activation) and has proven to be useful in the diagnosis of IgE-mediated allergies. After activation, CD63 can be measured S Garrido,1 JA Cumplido,1 A Rábano,2 D Martínez,1 C Blanco,1 by fl ow cytometry, using stimulation control with anti-IgE as a positive control [6-8]. However, in the present report, we 1Department of Allergology, Hospital Universitario de Gran were unable to demonstrate the immunological pathway since Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain stimulation with anti-IgE showed no activation. Furthermore, even 2Department of Pharmacy, Hospital Universitario de Gran though the short time between the inhalation and the reaction onset Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain and the fact that patient was reproducibly rechallenged, suggesting a type I reaction, IgE antibodies could not be detected. Key words: Proton pump inhibitors. Omeprazole. Drug allergy. We present a case of an anaphylactic reaction after salbutamol administration. Physicians must be aware of the Palabras clave: Inhibidores de la bomba de protones. Omeprazol. possibility that drugs used in the treatment of allergic reactions Alergia a medicamentos. Hipersensibilidad. Reactividad may occasionally act as the causal agent itself.
Proton pump inhibitors (PPIs) are modifi ed benzimidazoles that include omeprazole, pantoprazole, lansoprazole, 1. Martindale. The complete drug reference. In: Sweetman SC, rabeprazole, and esomeprazole. They constitute the treatment Blake PS, McGlashan JM, Pearsons JM, editors. The complete of choice in acid refl ux and peptic ulcer diseases. A few drug reference. London: Pharmaceutical Press; 2002. p. 887- cases of immunoglobulin (Ig) E-mediated hypersensitivity to omeprazole have been reported in which cross-reactivity 2. Spooner LM, Olin JL. Paradoxical bronchoconstriction with among all PPIs is frequently assumed [1-3]. We describe a case albuterol administered by metered-dose inhaler and nebulizer of anaphylaxis to omeprazole and analysis of cross-reactivity solution. Ann Pharmacother. 2005;39:1924-27.
through an exhaustive diagnostic procedure. 3. Mutlu GM, Moonjelly E, Chan L, Olopade CO. Laryngospasm A 45-year-old woman presented with acute itching of the and paradoxical bronchoconstriction after repeated doses of palms and soles, diffuse erythema, and breathlessness 3 days beta 2-agonists containing edentate disodium. Mayo Clin Proc. after heminephrectomy. An unclear temporal relationship was observed with the intravenous drugs administered: 4. Finnerty JP, Howarth PH. Paradoxical bronchoconstriction with dexketoprofen, ciprofl oxacin, ranitidine, metamizole, and nebulized albuterol but not with terbutaline. Am Rev Respir Dis. omeprazole. Twenty days later, she presented a similar episode with vomiting and diarrhea an hour after ingesting a 20 mg 5. Bonniaud P, Favrolt N, Collet E, Dumas JP, Guilloux L, Pauli G, omeprazole tablet for epigastralgia. She was diagnosed with Camus P. Salbutamol, terbutaline and pirbuterol allergy in an gastroenteritis in the emergency department.
asthmatic patient. Allergy. 2007 Oct;62(10):1219-20. Intradermal and skin prick tests (SPT) were performed 6. Sainte Laudy J. Application of fl ow cytometry to the analysis of with dexketoprofen, ciprofl oxacin, ranitidine, magnesium activation of human basophils. Immunologic validation of the metamizole, and omeprazole. Negative results were obtained method. Allerg Immunol (Paris). 1998; 30:41-5. with all of the tested drugs except omeprazole. Histamine 7. Sanz ML, Maselli JP, Gamboa PM, García-Avilés MC, Oehling A, and saline were used as positive and negative controls, Diéguez I, de Weck AL. Flow-cytometric basophil activation test. respectively. Controlled oral challenges were performed with A review. J Investig Allergol Clin Immunol. 2002;12:143-54.
dexketoprofen, ciprofl oxacin, ranitidine, and metamizole, all J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142 Short Communications and Brief Case Notes of which were well tolerated. The patient provided informed PPI allergy, one dependent on the shared pyridine ring that consent to the skin tests and oral challenges. would explain the cross-reactivity among the whole group and In order to identify alternative treatments, PPIs were tested the other dependent on the side chain that would explain the by SPT and intradermal test. All PPI solutions were prepared in selective hypersensitivity to lansoprazole and rabeprazole.
our laboratory under sterile conditions in a horizontal laminar In conclusion, when PPI allergy is suspected, we suggest fl ow cabinet. Solutions were fi ltered through membranes with a study including all PPIs to consider selective oral challenges a pore size of 0.22 ␮m. Omeprazole and pantoprazole were or avoidance of the whole group, as in our case.
prepared at concentrations of 40 mg/mL by dissolving the corresponding lyophilized drugs (Losec 40 mg and Pantocarm References
40 mg) in 1 mL of 0.9% saline. Lansoprazole, rabeprazole, and esomeprazole solutions were prepared from enteric-coated 1. Galindo PA, Borja J, Feo F, Gomez E, Garcia R, Cabrera M, tablets (Opiren 30 mg, Pariet 20 mg, and Nexium Mups 20 mg, Martinez C. Anaphylaxis to omeprazole. Ann Allergy Asthma respectively) by crushing in a mortar and adding 1 mL of 0.9% saline to produce 30 mg/mL, 20 mg/mL, and 20 mg/mL 2. Natsch S, Vinks MH, Voogt AK, Mees EB, Meyboom RH. solutions, respectively. The stock solutions were kept at 4ЊC Anaphylactic reactions to proton-pump inhibitors. Ann for no more than 24 hours. SPT was performed directly with the stock solutions and intradermal tests were done with the 3. Garmendia Zallo M, Sanchez Azkarate A, Kraemer Mbula R, stock solutions and 3 serial dilutions (1:10, 1:100, and 1:1000, Liarte Ruano I, Nunez Hernandez A, Cid De Rivera C. Cross v/v), in each case starting with the lowest concentration and reactivity among proton pump inhibitors: does it exist?. Allergol stopping when a positive result was obtained.
SPT was positive for omeprazole (wheal diameter, 16 mm), 4. Gonzalez P, Soriano V, Lopez P, Niveiro E. Anaphylaxis to proton pantoprazole (6 mm), and rabeprazole (5 mm). Intradermal pump inhibitors. Allergol Immunopathol. 2002;30:342-3.
tests at the lowest dilution (1:1000, v/v) showed a positive 5. Perez Pimiento AJ, Prieto Lastra L, Rodriguez Cabreros MI, result in all cases: omeprazole (15 mm), pantoprazole (11 mm), Gonzalez Sanchez LA, Mosquera MR, Cubero AG. Hypersensitivity lansoprazole (10 mm), rabeprazole (8 mm), and esomeprazole to lansoprazole and rabeprazole with tolerance to other proton (10 mm). Because of the severity of the reaction and the results pump inhibitors. J Allergy Clin Immunol. 2006;117:707-8.
of the skin tests, we decided not to perform controlled oral 6. Porcel S, Rodriguez A, Jimenez S, Alvarado M, Hernandez J. challenge tests. SPT and intradermal tests (1:100 and 1:1000, Allergy to lansoprazole: study of cross-reactivity among proton- v/v) with the 5 PPIs were performed in 5 nonatopic subjects, pump inhibitors. Allergy. 2005;60:1087-8.
Various doses of PPIs have been used previously in skin tests [3- 5]. In our experience, PPI extracts at the concentration described ❚ Manuscript received August 21, 2007; accepted for publication above for SPT and dilutions of 1:100 and 1:1000 for intradermal tests are safe and informative. Other authors have also used similar concentrations for cutaneous tests, showing a high specifi city [6].
Sara Garrido Fernández
Although cross-reactivity among PPIs has usually Hospital Universitario de Gran Canaria Dr. Negrín been assumed [1-3], selective allergies to lansoprazole and rabeprazole have recently been reported [5,6]. This selective pattern could be based on the homology between their side chains and not on the common pyridine central ring (Figure). Therefore, 2 different patterns of response seem to exist in Occupational Asthma and Rhinoconjunctivitis
Caused by Cricket Allergy

J Bartra,1 J Carnés,2 R Muñoz-Cano,1 I Bissinger,1 C Picado,1 AL Valero11 Allergy Unit, Pneumology Department, Hospital Clinic, Barcelona, Spain2 Laboratorios LETI, Tres Cantos, Madrid, Spain Key words: Allergy. Contact urticaria. Cricket. Occupational asthma. Rhinoconjunctivitis. Palabras clave: Alergia. Asma ocupacional. Grillo. Urticaria de Allergic occupational asthma can be caused by a number Figure. Chemical structure of proton pump inhibitors. of substances, mostly proteins, derived from animals, plants, J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142 Short Communications and Brief Case Notes foods, and enzymes. Insect exposure is not very common phosphate buffered saline was negative. Specifi c nasal challenge in Western countries. However, laboratory workers or other test with cricket extract was performed in a control patient professional groups may have direct contact with these animals. with a negative result. The protein profi le of the cricket extract Nowadays, many insect species belonging to different orders showed several bands with a molecular weight range of 10 to have been implicated in allergic processes [1]. It has been 100 kDa. Immunoblot experiments showed several bands with estimated that 50% of animal-sensitized individuals will develop immunoglobulin (Ig) E binding capacity. The most prominent rhinoconjunctivitis, 25% skin reactions, and 25% asthma, and bands corresponded to proteins with a molecular weight of 17, most allergic processes in these individuals affect multiple 32, 47, and 62 kDa. No bands were recognized with a pool of sera from healthy control individuals (Figure). We present a patient with occupational asthma and Patients with IgE sensitization to crickets, without evidence rhinoconjunctivitis caused by inhaling cricket (Acheta of clinical relevance, have been reported in previous studies and campestris) particles and contact urticaria after handling of most of them showed cross reactivity with other insects [4,5]. crickets. A 28-year-old man with no previous personal history Bagenstose et al [6] reported 2 patients whose clinical history of asthma or other respiratory disorders and who had never strongly suggested an asthma-related allergy linked to their smoked came to our allergy unit with a 4-year history of frequent occupation, but the diagnosis was not confi rmed by respiratory episodes of cough, dyspnea, and wheezing accompanied by function tests. Crickets appeared to be involved. The suspected rhinoconjunctivitis and occasionally chemosis and urticaria. cricket allergy was confi rmed by a skin test and bronchial He had worked for 7 years as an assistant in a reptile shop, inhalation challenge. However, both patients were sensitized where he fed reptiles with live crickets, which themselves to several common aeroallergens and also other allergens they were fed with cornmeal. He developed the symptoms after were exposed to in their jobs, including crickets. a latent period of 3 years. The patient reported improvement In conclusion, this is the fi rst reported case of unequivocal of the respiratory symptoms and disappearance of cutaneous occupational asthma and rhinoconjunctivitis with contact symptoms at the weekend and during holidays. urticaria in a patient monosensitized to cricket. The clinical Skin prick tests with a battery of common inhalant allergens, relevance was demonstrated by specifi c nasal challenge test including dust mites, pollens, moulds, cat and dog dander, and measured by acoustic rhinometry. More studies are necessary to insect (German cockroach, oriental cockroach, and American determine the immunochemical characteristics of the allergens cockroach), were negative. Skin prick test with a manufactured and cross-reactivity with other insect groups. cricket extract at a concentration of 1 mg of freeze-dried material per milliliter was positive (7 mm wheal diameter) and negative References
in 5 control individuals. Skin prick test (prick by prick) with a cornmeal extract was negative. Spirometric values were in 1. Lopata A, Fenemore B, Jeebhay MF, Gade G, Potter PC. the normal range (forced vital capacity [FVC], 5.18 L [89% of Occupational allergy in laboratory workers caused by the predicted]; forced expiratory volume in 1 second, 4.11 L [89% of African migratory grasshopper Locusta migratoria. Allergy. predicted]; forced expiratory fl ow at 25%-75% of FVC, 3.68 L/s [80% of predicted]) and the results of a bronchodilator test were 2. Gautrin D, Ghezzo H, Infante-Rivard C, Malo JL. Host negative. Serial determinations of peak expiratory fl ow were determinants for the development of allergy in apprentices seen to drop by more than 20% during work periods and returned exposed to laboratory animals. Eur respir J. 2002;19:96-103.
to normal values at the weekend. A specifi c nasal challenge test, 3. Tee RD, Gordon DJ, Hawkins ER, Nunn AJ, Lacey J, Venables measured with acoustic rhinometry, was performed with a cricket KM, Cooter RJ, McCaffery AR, Newman Taylor AJ. Occupational extract and showed an immediate response at 1:1000 dilution allergy to locusts: an investigation of the sources of the allergen. of the extract used in the prick test, with a reduction in nasal J Allergy Clin Immunol. 1988;81:505-508.
volume of more than 30% between the 2nd and 5th centimeter 4. Lierl MB, Riordan MM, Fisher TJ. Prevalence of insect allergen- into the nostrils measured at 10 minutes. A nasal challenge with specifi c IgE in allergic asthmatic children in Cincinnati-Ohio. Ann Allergy. 1994;72:45-50.
5. Mairesse M, Ledent C. Allergy and fi shing activities. Allergol 6. Bagenstose AH, Mathews KP, Homburger HA, Saaveard- Delgado AP. Inhalant allergy due to crickets. J Allergy Clin ❚ Manuscript received October 17, 2007; accepted for publication December 4, 2007. Joan Bartra
patient’s serum; lane 2, control serum. J Investig Allergol Clin Immunol 2008; Vol. 18(2): 136-142

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Microsoft word - hsa preventive list 2.19.14

2/19/14 Guidance regarding Waiver of Deductible for Preventive Medications Covered Under High Deductible Health Plans Designed for Use With a Health Savings Account. This guide applies only to certain high deductible health plans designed for use with a health savings account. It applies only for specific large groups that have elected this preventive medication benefit. If you are not certain whe

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