- Email: [email protected]
Adverse reactions to the allergen conjunctival provocation test
onstrate response disagreement. The statistic decreased and disagreement level increased with age, with similar results by race, but none of these were statistically significant. Responses to binary asthma questions demonstrated 93% to 97% agreement, with good to excellent (0.75-0.91). Quantitative asthma symptoms demonstrated 81% to 86% agreement, with a moderate to good (0.59-0.7). Chest tightness or cough after activity or night wakening demonstrated 81% to 86% agreement, with a moderate to good (0.59-0.67). Overall, student responses matched their parents’ responses regarding quantitative asthma questions. The most concordant response was seen in asthma medication use (97% agreement, ⫽ 0.91), diagnosis of asthma (96% agreement, ⫽ 0.89), hospitalization for respiratory problems (94% agreement, ⫽ 0.78), and missed school days due to breathing problems (93% agreement, ⫽ 0.75), indicating both parents and students have good recognition of the student’s condition. Discordant responses to the question “develops a cough that won’t go away?” may indicate unclear wording, misinterpretation, or that students may be more in tune with their daily symptoms. Decreased agreement with increasing age may occur due to increased time older students are away from their caregivers. Persistent, indolent symptoms may go unnoticed by the parent but have significant effects on the child. In contrast, good agreement was seen on hospitalizations or missed school day responses because these likely affect both parties. Parent-student agreement in responses did not differ by race/ ethnicity or language of questionnaire (English or Spanish). Our study generally showed good agreement between parent and student responses for asthma. Disagreement was seen most in responses to questions that were more dependent on self-perception of symptoms, but these were not statistically significant. Also, no significant racial/ethnic or language differences in parent-student agreement were seen. This study suggests that screening surveys given to either parent or elementary students may be a simple, cost-effective mechanism for identifying children in an urban school population who may need further evaluation. SACHIN N. BAXI, MD*‡ WILLIAM J. SHEEHAN, MD*‡ JONATHAN M. GAFFIN, MD†‡ JIRAWADEE YODYING, MD§ SIRADA PANUPATTANAPONG, MD§ JEFFREY P. LANE, CIH, MPH储 CHUNXIA FU, MS¶ ELAINE B. HOFFMAN, PHD# DIANE R. GOLD, MD, MPH¶# WANDA PHIPATANAKUL, MD, MS*‡# *Department of Pediatrics Division of Allergy and Immunology Children’s Hospital Boston, Massachusetts †Department of Pediatrics Division of Respiratory Diseases Children’s Hospital Boston, Massachusetts ‡Harvard Medical School Boston, Massachusetts §Department of Medicine Siriraj Hospital Mahidol University Medical School Mahidol, Thailand
VOLUME 107, OCTOBER, 2011
储Facilities Management ¶Department of Biostatistics Harvard School of Public Health Boston, Massachusetts #Channing Laboratory Department of Medicine Brigham and Women’s Hospital Boston, Massachusetts [email protected] 1. Knorr RS, Condon SK, Dwyer FM, et al. Tracking pediatric asthma: the Massachusetts experience using school health records. Environ Health Perspect. 2004;112:1424–1427. 2. Redline S, Gruchalla RS, Wolf RL, et al. Development and validation of schoolbased asthma and allergy screening questionnaires in a 4-city study. Ann Allergy Asthma Immunol. 2004;93:36 – 48. 3. Gruchalla RS, Gan V, Roy L, et al. Results of an inner-city school-based asthma and allergy screening pilot study: a combined approach using written questionnaires and step testing. Ann Allergy Asthma Immunol. 2003;90:491– 499. 4. Redline S, Larkin EK, Kercsmar C, et al. Development and validation of schoolbased asthma and allergy screening instruments for parents and students. Ann Allergy Asthma Immunol. 2003;90:516 –528. 5. Mata Fernandez C, Fernandez-Benitez M, Perez Miranda M, et al. Validation of the Spanish version of the Phase III ISAAC questionnaire on asthma. J Investig Allergol Clin Immunol. 2005;15:201–210. 6. Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8:483– 491.
ADVERSE REACTIONS TO THE ALLERGEN CONJUNCTIVAL PROVOCATION TEST The conjunctival provocation test (CPT) is a well-established method for diagnosing allergic conjunctivitis to a suspected allergen in sensitized patients because it reproduces signs and symptoms of the disease. It usually provokes either an early-phase or, less commonly, a late-phase conjunctival reaction.1 There are few reports of adverse reactions during CPT, which is considered a safe procedure. Abelson et al2 performed 950 ocular challenges and found only 2 mild systemic reactions in sensitized patients, 1 case of mild bronchoconstriction in an asthmatic patient and 1 case of late-onset urticaria. No generalized reactions were reported in other studies with large series of patients3 and high doses of allergens.4 However, Anderson et al5 described a 48-year-old woman who developed nasal discharge, sneezing, and mild wheezing immediately after CPT with mixed grass pollen extract. The episode was attributed to allergen absorption through the conjunctiva or the upper aerodigestive tract or by inhalation. Núñez and Cuesta6 described 2 patients who during local conjunctival immunotherapy with Dermatophagoides pteronyssinus experienced itching and tearing to a dose of 1,000 AU/mL (Greer Laboratories Inc, Lenoir, North Carolina). One refused to continue treatment, and the other tolerated a lower dose of 100 AU/mL. This study is part of a protocol aimed to verify the relationship of nonspecific conjunctival hyperreactivity to specific allergic hyperreactivity in patients with ocular symptoms.7 We performed 82 CPTs with standardized allergens (ALK Abelló-FDA Allergenic, Rio de Janeiro, Brazil) in 20 L of solution in patients with allergic rhinoconjunctivitis: 26 with D pteronyssinus (83.8 g/mL of Der p 1), 26 with Blomia tropicalis (462.5 ng/mL of Blo t 5), and 30 with Lolium perenne (399.2 g/mL of Phl p 5). There were 77 positive ocular challenge results (94%). All tests were performed out of grass Disclosures: Authors have nothing to disclose. © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.anai.2011.07.015
373
5. Anderson DF, McGill JI, Roche WR. Improving the safety of conjunctival provocation tests. J Allergy Clin Immunol. 1996;98:1000. 6. Núñez JA, Cuesta U. Local conjunctival immunotherapy: the effect of Dermatophagoides pteronyssinus local conjunctival immunotherapy on conjunctival provocation test in patients with allergic conjunctivitis. Allergol Immunopathol. 2000;28: 301–306. 7. Mourão EMM, Rosário NA, Silva L, Shimakura SE. Ocular symptoms in nonspecific conjunctival hyperreactivity. Ann Allergy Asthma Immunol. 2011;107:29 –34.
Figure 1. Severe chemosis, redness, and eyelid swelling in a grass pollen sensitive patient during a conjunctival provocation test with 25 g/mL of Phl p 5.
pollen season, when patients were asymptomatic and not taking antiallergic medication. In 68 patients (88%), mild nasal symptoms, such as itching, sneezing, nasal congestion, and aqueous rhinorrhea, occurred after a positive ocular challenge result. Symptoms spontaneously waned within 1 hour. Lower lid swelling was observed in 41 of 77 patients (53%) with positive CPT results. A grass pollen sensitive patient had a severe periocular edema (Fig 1) that lasted for 2 days and started immediately when the allergen was applied to the eye, requiring a short course of oral histamine1 (H1)–antihistamine and corticosteroids. Two other patients, also allergic to L perenne, reacted to a positive ocular challenge with eyelid swelling that lasted up to 3 hours despite local and oral H1-antihistamines. Severe chemosis followed by epiphora and ocular itching occurred in another grass pollen sensitive patient who required an ocular pad for 8 hours and corticosteroid eye drops to control this acute conjunctival reaction. All patients had mean wheal diameters of 10 mm or greater at skin prick testing. Acute respiratory distress and wheezing were observed after a positive CPT result with B tropicalis in a well-controlled asthmatic patient (8-mm skin wheal) not requiring any medication in the previous 8 months that successfully responded to inhaled shortacting 2-agonist and oral H1-antihistamine and prednisolone. The adverse reactions reported here are probably related to the dose of allergen in marked sensitivity to grass pollen in 4 patients (12.5, 49.9, 25, and 25 g/mL of Phl p 5, respectively) and to B tropicalis in 1 patient (28.9 g/mL of Blo t 5). Our observation could not be compared with other studies of ocular provocation in which nonstandardized allergens were used. Allergic conjunctivitis is usually a clinical diagnosis. CPT is a useful tool to confirm IgE-mediated reaction to allergens and is used in clinical trials of antiallergic treatment. It should be conducted by experienced physicians preferably in hospital setting with treatment facilities available for potential local and systemic adverse reactions. ELIZABETH MARIA MERCER MOURÃO, MD* NELSON AUGUSTO ROSÁRIO, MD, PHD† *Department of Internal Medicine †Department of Pediatrics Federal University of Paraná Curitiba, Brazil 1. Bacon AS, Ahluwalia P, Irani AM, et al. Tear and conjunctival changes during the allergen induced early and late phase responses. J Allergy Clin Immunol. 2000;106: 948 –954. 2. Abelson MB, Chambers WA, Smith LM. Conjunctival allergen challenge: a clinical approach to studying allergic conjunctivitis. Arch Ophthalmol. 1990;108:84 – 88. 3. Aichane A, Campbell AM, Chanal I, et al. Precision of conjunctival provocation tests in right and left eyes. J Allergy Clin Immunol. 1993;92:49 –55. 4. Bonini S, Bonini S, Bucci MG, et al. Allergen dose response and late symptoms in a human model of ocular allergy. J Allergy Clin Immunol. 1990;86:869 – 876.
374
SEVERE STEROID-DEPENDENT IDIOPATHIC ANGIOEDEMA WITH RESPONSE TO RITUXIMAB We describe a 19-year-old woman with recurrent episodes of severe angioedema involving airway compromise and multiple emergency department (ED) visits, culminating in a steroid-dependent, prolonged hospitalization and the failure of several typical, first-line, steroid-sparing agents. The patient gave consent for this publication. Her first episode, which occurred in July 2009, involved her tongue, throat, lips, and face, with associated malaise, nausea, and vomiting. She was treated with oral antihistamines and her symptoms resolved. Subsequent episodes, however, were more severe and required aggressive management in the ED but always resolved quickly with epinephrine. Symptoms were always limited to tongue, lip, and throat swelling and hoarse voice (presumed laryngeal edema) but were severe, with a complete inability to swallow or breathe normally. She had a history of asthma, which was well controlled with budesonide-formoterol and montelukast. Review of systems revealed photosensitivity but no malar rash. She had no human immunodeficiency virus, hepatitis B, or hepatitis C risk factors. There was no history of oral contraceptive use or any other medications, including nonsteroidal anti-inflammatory drugs. She was assessed in the allergy/immunology clinic during an asymptomatic interval, with negative skin test results to a limited panel of environmental and food allergens (she had been told milk allergy was likely causal during one of her ED visits). Laboratory tests were ordered (Table 1), and prophylactic therapy was initiated with cetirizine, 20 mg twice daily, and ranitidine, 150 mg twice daily. Despite this, she had repeated, severe episodes that required multiple and higher doses of epinephrine in the ED, one of which led to a 48-hour admission with intravenous corticosteroid treatment (methylprednisolone, 80 mg intravenously every 8 hours). After she was discharged, however, oral prednisone maintenance failed, leading to readmission 36 hours later. She required intramuscular epinephrine on presentation, was given methylprednisolone, 125 mg intravenously every 8 hours, and continued to take histamine1/ histamine2 blockers and montelukast. Direct laryngoscopy confirmed the absence of structural abnormalities; recurrent episodes of angioedema with associated voice hoarseness were witnessed by caregivers and both authors of this letter. Episodes of angioedema always responded promptly to epinephrine and/or within hours of intravenous steroid administration. Because of ongoing epinephrine requirements (1-2 injections daily), her steroid interval was adjusted first to every 6 hours and then to every 4 hours; at this interval of intravenous steroid administration, her episodes were fully controlled with no epinephrine requirements. An empiric course of C1 esterase inhibitor was ineffective; C1
Disclosures: Authors have nothing to disclose. © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.anai.2011.07.003
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
VOLUME 107, OCTOBER, 2011
储Facilities Management ¶Department of Biostatistics Harvard School of Public Health Boston, Massachusetts #Channing Laboratory Department of Medicine Brigham and Women’s Hospital Boston, Massachusetts [email protected] 1. Knorr RS, Condon SK, Dwyer FM, et al. Tracking pediatric asthma: the Massachusetts experience using school health records. Environ Health Perspect. 2004;112:1424–1427. 2. Redline S, Gruchalla RS, Wolf RL, et al. Development and validation of schoolbased asthma and allergy screening questionnaires in a 4-city study. Ann Allergy Asthma Immunol. 2004;93:36 – 48. 3. Gruchalla RS, Gan V, Roy L, et al. Results of an inner-city school-based asthma and allergy screening pilot study: a combined approach using written questionnaires and step testing. Ann Allergy Asthma Immunol. 2003;90:491– 499. 4. Redline S, Larkin EK, Kercsmar C, et al. Development and validation of schoolbased asthma and allergy screening instruments for parents and students. Ann Allergy Asthma Immunol. 2003;90:516 –528. 5. Mata Fernandez C, Fernandez-Benitez M, Perez Miranda M, et al. Validation of the Spanish version of the Phase III ISAAC questionnaire on asthma. J Investig Allergol Clin Immunol. 2005;15:201–210. 6. Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8:483– 491.
ADVERSE REACTIONS TO THE ALLERGEN CONJUNCTIVAL PROVOCATION TEST The conjunctival provocation test (CPT) is a well-established method for diagnosing allergic conjunctivitis to a suspected allergen in sensitized patients because it reproduces signs and symptoms of the disease. It usually provokes either an early-phase or, less commonly, a late-phase conjunctival reaction.1 There are few reports of adverse reactions during CPT, which is considered a safe procedure. Abelson et al2 performed 950 ocular challenges and found only 2 mild systemic reactions in sensitized patients, 1 case of mild bronchoconstriction in an asthmatic patient and 1 case of late-onset urticaria. No generalized reactions were reported in other studies with large series of patients3 and high doses of allergens.4 However, Anderson et al5 described a 48-year-old woman who developed nasal discharge, sneezing, and mild wheezing immediately after CPT with mixed grass pollen extract. The episode was attributed to allergen absorption through the conjunctiva or the upper aerodigestive tract or by inhalation. Núñez and Cuesta6 described 2 patients who during local conjunctival immunotherapy with Dermatophagoides pteronyssinus experienced itching and tearing to a dose of 1,000 AU/mL (Greer Laboratories Inc, Lenoir, North Carolina). One refused to continue treatment, and the other tolerated a lower dose of 100 AU/mL. This study is part of a protocol aimed to verify the relationship of nonspecific conjunctival hyperreactivity to specific allergic hyperreactivity in patients with ocular symptoms.7 We performed 82 CPTs with standardized allergens (ALK Abelló-FDA Allergenic, Rio de Janeiro, Brazil) in 20 L of solution in patients with allergic rhinoconjunctivitis: 26 with D pteronyssinus (83.8 g/mL of Der p 1), 26 with Blomia tropicalis (462.5 ng/mL of Blo t 5), and 30 with Lolium perenne (399.2 g/mL of Phl p 5). There were 77 positive ocular challenge results (94%). All tests were performed out of grass Disclosures: Authors have nothing to disclose. © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.anai.2011.07.015
373
5. Anderson DF, McGill JI, Roche WR. Improving the safety of conjunctival provocation tests. J Allergy Clin Immunol. 1996;98:1000. 6. Núñez JA, Cuesta U. Local conjunctival immunotherapy: the effect of Dermatophagoides pteronyssinus local conjunctival immunotherapy on conjunctival provocation test in patients with allergic conjunctivitis. Allergol Immunopathol. 2000;28: 301–306. 7. Mourão EMM, Rosário NA, Silva L, Shimakura SE. Ocular symptoms in nonspecific conjunctival hyperreactivity. Ann Allergy Asthma Immunol. 2011;107:29 –34.
Figure 1. Severe chemosis, redness, and eyelid swelling in a grass pollen sensitive patient during a conjunctival provocation test with 25 g/mL of Phl p 5.
pollen season, when patients were asymptomatic and not taking antiallergic medication. In 68 patients (88%), mild nasal symptoms, such as itching, sneezing, nasal congestion, and aqueous rhinorrhea, occurred after a positive ocular challenge result. Symptoms spontaneously waned within 1 hour. Lower lid swelling was observed in 41 of 77 patients (53%) with positive CPT results. A grass pollen sensitive patient had a severe periocular edema (Fig 1) that lasted for 2 days and started immediately when the allergen was applied to the eye, requiring a short course of oral histamine1 (H1)–antihistamine and corticosteroids. Two other patients, also allergic to L perenne, reacted to a positive ocular challenge with eyelid swelling that lasted up to 3 hours despite local and oral H1-antihistamines. Severe chemosis followed by epiphora and ocular itching occurred in another grass pollen sensitive patient who required an ocular pad for 8 hours and corticosteroid eye drops to control this acute conjunctival reaction. All patients had mean wheal diameters of 10 mm or greater at skin prick testing. Acute respiratory distress and wheezing were observed after a positive CPT result with B tropicalis in a well-controlled asthmatic patient (8-mm skin wheal) not requiring any medication in the previous 8 months that successfully responded to inhaled shortacting 2-agonist and oral H1-antihistamine and prednisolone. The adverse reactions reported here are probably related to the dose of allergen in marked sensitivity to grass pollen in 4 patients (12.5, 49.9, 25, and 25 g/mL of Phl p 5, respectively) and to B tropicalis in 1 patient (28.9 g/mL of Blo t 5). Our observation could not be compared with other studies of ocular provocation in which nonstandardized allergens were used. Allergic conjunctivitis is usually a clinical diagnosis. CPT is a useful tool to confirm IgE-mediated reaction to allergens and is used in clinical trials of antiallergic treatment. It should be conducted by experienced physicians preferably in hospital setting with treatment facilities available for potential local and systemic adverse reactions. ELIZABETH MARIA MERCER MOURÃO, MD* NELSON AUGUSTO ROSÁRIO, MD, PHD† *Department of Internal Medicine †Department of Pediatrics Federal University of Paraná Curitiba, Brazil 1. Bacon AS, Ahluwalia P, Irani AM, et al. Tear and conjunctival changes during the allergen induced early and late phase responses. J Allergy Clin Immunol. 2000;106: 948 –954. 2. Abelson MB, Chambers WA, Smith LM. Conjunctival allergen challenge: a clinical approach to studying allergic conjunctivitis. Arch Ophthalmol. 1990;108:84 – 88. 3. Aichane A, Campbell AM, Chanal I, et al. Precision of conjunctival provocation tests in right and left eyes. J Allergy Clin Immunol. 1993;92:49 –55. 4. Bonini S, Bonini S, Bucci MG, et al. Allergen dose response and late symptoms in a human model of ocular allergy. J Allergy Clin Immunol. 1990;86:869 – 876.
374
SEVERE STEROID-DEPENDENT IDIOPATHIC ANGIOEDEMA WITH RESPONSE TO RITUXIMAB We describe a 19-year-old woman with recurrent episodes of severe angioedema involving airway compromise and multiple emergency department (ED) visits, culminating in a steroid-dependent, prolonged hospitalization and the failure of several typical, first-line, steroid-sparing agents. The patient gave consent for this publication. Her first episode, which occurred in July 2009, involved her tongue, throat, lips, and face, with associated malaise, nausea, and vomiting. She was treated with oral antihistamines and her symptoms resolved. Subsequent episodes, however, were more severe and required aggressive management in the ED but always resolved quickly with epinephrine. Symptoms were always limited to tongue, lip, and throat swelling and hoarse voice (presumed laryngeal edema) but were severe, with a complete inability to swallow or breathe normally. She had a history of asthma, which was well controlled with budesonide-formoterol and montelukast. Review of systems revealed photosensitivity but no malar rash. She had no human immunodeficiency virus, hepatitis B, or hepatitis C risk factors. There was no history of oral contraceptive use or any other medications, including nonsteroidal anti-inflammatory drugs. She was assessed in the allergy/immunology clinic during an asymptomatic interval, with negative skin test results to a limited panel of environmental and food allergens (she had been told milk allergy was likely causal during one of her ED visits). Laboratory tests were ordered (Table 1), and prophylactic therapy was initiated with cetirizine, 20 mg twice daily, and ranitidine, 150 mg twice daily. Despite this, she had repeated, severe episodes that required multiple and higher doses of epinephrine in the ED, one of which led to a 48-hour admission with intravenous corticosteroid treatment (methylprednisolone, 80 mg intravenously every 8 hours). After she was discharged, however, oral prednisone maintenance failed, leading to readmission 36 hours later. She required intramuscular epinephrine on presentation, was given methylprednisolone, 125 mg intravenously every 8 hours, and continued to take histamine1/ histamine2 blockers and montelukast. Direct laryngoscopy confirmed the absence of structural abnormalities; recurrent episodes of angioedema with associated voice hoarseness were witnessed by caregivers and both authors of this letter. Episodes of angioedema always responded promptly to epinephrine and/or within hours of intravenous steroid administration. Because of ongoing epinephrine requirements (1-2 injections daily), her steroid interval was adjusted first to every 6 hours and then to every 4 hours; at this interval of intravenous steroid administration, her episodes were fully controlled with no epinephrine requirements. An empiric course of C1 esterase inhibitor was ineffective; C1
Disclosures: Authors have nothing to disclose. © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.anai.2011.07.003
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY