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Coronary and laryngeal spasm provoked by methacholine inhalation
392 Letters to the Editor
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J ALLERGY CLIN IMMUNOL FEBRUARY 2001
steroid insensitivity in human PBMCs by microbial superantigens. J Allergy Clin Immunol 2000;105:782-7. Boguniewicz M, Fiedler VC, Raimer S, Lawrence ID, Leung DYM, Hanifin JM. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J Allergy Clin Immunol 1998;102:637-44. Ruzicka T, Bieber T, Schopf E, Rubins A, Dobozy A, Bos JD, et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 1997;337:816-21. Tsytsykova AV, Goldfeld AE. Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock. J Exp Med 2000;192:581-6. Bieber T. Topical tacrolimus (FK 506): a new milestone in the management of atopic dermatitis. J Allergy Clin Immunol 1998;102:555-7.
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1/8/112848 doi:10.1067/mai.2001.112848
Coronary and laryngeal spasm provoked by methacholine inhalation To the Editor: A 34-year-old flight attendant was referred for evaluation of possible allergy to bleaching powder. She described a 12-month history of symptoms of wheezing, light-headedness, nausea, and dysphonia and an anaphylactic reaction on smelling chlorine and other strong odors of cleaning solutions in the aircraft. For these symptoms, she had numerous admissions to hospital emergency departments and had received treatment for anaphylaxis and asthma with subcutaneous and intravenous adrenaline, corticosteroids, and bronchodilators. However, objective evidence of variable or reversible airflow limitation was never established. Two months earlier, she had had similar symptoms during a contrast-enhanced computed tomography scan of her abdomen to investigate a possible loin mass. On the basis of her previous history of anaphylaxis, she was given intravenous epinephrine and corticosteroids, shortly after which she experienced central chest tightness and nausea. Her electrocardiogram (ECG) (Fig 1, A) showed T-wave inversion in the inferior limb leads. Her troponin (15 ng/mL) and creatine kinase (284 IU; MB isoenzyme fraction, 42%) levels were raised. Findings of a coronary angiogram, a technetium Tc 99m sestamibi exercise perfusion scan, and an echocardiogram 5 days later were normal. Her chest radiograph and blood autoantibody profile findings were normal. She had regular symptoms of heartburn, acid regurgitation, and arthralgia and was taking levothyroxine for hypothyroidism. She had never smoked. We considered her symptoms to be consistent with laryngeal dysfunction (confirmed by direct laryngoscopy), hyperventilation, and gastroesophageal reflux. She was nonatopic (negative allergy skin prick test result and normal total serum IgE level) and had normal spirometry findings, ECG (Fig 1, B) findings, and cell counts in induced sputum. A methacholine inhalation test was performed by the tidal breathing method.1Immediately after inhalation of methacholine 16 mg/mL, she lost her voice and had central chest pain and sweating. The maximal inspiratory flow-volume curve (Fig 2) showed a variable extrathoracic obstructive pattern consistent with laryngeal dysfunction. Her ECG showed T-wave inversion in the inferior leads (Fig 1, C). Her end-tidal PCO2 was 39 mm Hg. Cardiac enzyme levels were not raised, and the pain was relieved with sublingual nitroglycerine. The PC20 (provocative concentration of agonist producing a 20% fall in FEV1) methacholine was 12 mg/mL, indicating borderline normal airway responsiveness. She was later assessed by a cardiologist, who confirmed the diagnosis of syndrome X and prescribed diltiazem, aspirin, and omeprazole. She has been told that she does not have asthma or allergies and is currently undergoing voice therapy and psychiatric counseling. An ECG repeated 2 weeks later showed normal findings (Fig 1, D).
B
C
D FIG 1. A, ECG showing T-wave inversion in leads III and aVF following the administration of intravenous epinephrine, associated with central chest pain and raised troponin. B, Normal ECG 5 days after the episode of chest pain. C, ECG showing T-wave inversion in leads III and aVF following the inhalation of methacholine (16 mg/mL). D, Normal ECG 2 weeks after the methacholine inhalation test.
This is the first report of angina and coronary spasm after methacholine inhalation. The case also illustrates the use of the methacholine inhalation test to identify laryngeal dysfunction as a cause of asthmalike symptoms. The methacholine inhalation test is generally a safe procedure without any serious adverse effects.2 Although subcutaneous administration of methacholine has been reported to cause angina in patients with Prinzmetal’s variant angina pectoris,3 this has not been reported after a bronchial provocation test. We can only speculate on the mechanism of angina in our patient, who had a coronary-prone behavior pattern, possible syndrome X, epinephrine-induced myocardial necrosis,4 and gastroesophageal reflux.5 Chest pain relieved with nitroglycerine and associated with reversible ischemic changes in the ECG and normal coronary artery anatomy suggests coronary vasospasm as the cause of chest pain.
Letters to the Editor 393
J ALLERGY CLIN IMMUNOL VOLUME 107, NUMBER 2
Krishnan Parameswaran, MDa Gerard Cox, MBChBa Allan Kitching, MDb Frederick Hargreave, MDa aAsthma Research Group bDivision of Cardiology Department of Medicine St Joseph’s Hospital and McMaster University 50 Charlton Ave E Hamilton, Ontario, L8N 4A6, Canada REFERENCES 1. Juniper EF, Cockcroft DW, Hargreave FE. Histamine and methacholine inhalation tests: a laboratory tidal breathing protocol. 2nd ed. Lund, Sweden: Astra Draco AB; 1994. 2. Parameswaran KN, Inman MD, Ekholm BP, Morris MM, Summers E, O’Byrne PM, et al. Protection against methacholine bronchoconstriction to assess relative potency of inhaled β2-agonist. Am J Respir Crit Care Med 1999;160:354-7. 3. Stang JM, Kolibash AJ, Schorling JB, Bush CA. Methacholine provocation of Prinzmetal’s variant angina pectoris: a revised perspective. Clin Cardiol 1982;5:393-402. 4. Ferry DR, Henry RL, Kern MJ. Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arteries. Am Heart J 1986;111:1193-5. 5. Mellow MH, Simpson AG, Watt L, Schoolmeester L, Haye OL. Esophageal acid perfusion in coronary artery disease: induction of myocardial ischemia. Gastroenterology 1983;85:306-12. 6. Christopher KL, Wood RP 2d, Eckert RC, Blager FB, Raney RA, Souhrada JF. Vocal-cord dysfunction presenting as asthma. N Engl J Med 1983;308:1566-70.
1/8/112267 doi:10.1067/mai.2001.112267
Food intolerance due to wine gums: Identification of copper chlorophyll (E141) as a possible pseudoallergen
FIG 2. Flow volume curves before and after inhalation of 16 mg/mL concentration of methacholine showing flow limitation during maximal inspiratory effort.
The role of laryngeal dysfunction in provoking angina is less clear. However, in this patient the recognition of the disorder during a methacholine inhalation test was important in counseling the patient that she did not have asthma. A proper evaluation of her spirometry on her numerous previous admissions may have detected this, and an earlier diagnosis may have prevented her from getting multiple injections of epinephrine and experiencing myocardial necrosis. Laryngeal dysfunction is a common cause of pseudoasthma6; however, the prevalence of the condition in suspected occupational asthma is not known.
To the Editor: Food intolerance is a commonly perceived problem in the general population and may lead to a variety of symptoms. We present a report of a young woman with relapsing angioedema, rhinoconjunctivitis, and asthma-like symptoms caused by exposure to copper chlorophyll (E141). A 28-year-old woman had a history of sudden facial swelling associated with asthma-like symptoms and rhinorrhea. She remembered having eaten in a Chinese restaurant and having consumed various alcoholic beverages including a cocktail and an herb-flavored liqueur on the day of her symptoms. She had a history of allergic rhinoconjunctivitis and atopic eczema in her childhood. She also recalled symptoms of an oropharyngeal allergy syndrome after eating carrots, nuts, and kiwifruit. Her physical examination findings were unremarkable. Routine blood test results were normal including concentration and activity of serum C1-esterase inhibitor. Skin prick test results were positive against anise, caraway, mugwort, celery, coriander, paprika, carrot, nuts, and kiwifruit. Her total serum IgE level was elevated to 676 kU/L. Allergen-specific IgE antibodies against various spices and herbs were found in her serum. Allergic angioedema and rhinitis were diagnosed. She was advised to avoid the suspected foods and beverages and instructed to keep a food diary. One month later she again had multiple episodes of acute eyelid swelling, dyspnea, and rhinoconjunctivitis. Her food diary revealed that she had consumed milk, rice, orange juice, cheese, bread, 2 alcoholic cocktails, and English wine gums (a jelly bean–like chewy, sweet confection of different colors and fruit flavors without a hard sugar coat) as possible triggers. An open challenge was per-
7.
8.
9.
10.
J ALLERGY CLIN IMMUNOL FEBRUARY 2001
steroid insensitivity in human PBMCs by microbial superantigens. J Allergy Clin Immunol 2000;105:782-7. Boguniewicz M, Fiedler VC, Raimer S, Lawrence ID, Leung DYM, Hanifin JM. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J Allergy Clin Immunol 1998;102:637-44. Ruzicka T, Bieber T, Schopf E, Rubins A, Dobozy A, Bos JD, et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 1997;337:816-21. Tsytsykova AV, Goldfeld AE. Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock. J Exp Med 2000;192:581-6. Bieber T. Topical tacrolimus (FK 506): a new milestone in the management of atopic dermatitis. J Allergy Clin Immunol 1998;102:555-7.
A
1/8/112848 doi:10.1067/mai.2001.112848
Coronary and laryngeal spasm provoked by methacholine inhalation To the Editor: A 34-year-old flight attendant was referred for evaluation of possible allergy to bleaching powder. She described a 12-month history of symptoms of wheezing, light-headedness, nausea, and dysphonia and an anaphylactic reaction on smelling chlorine and other strong odors of cleaning solutions in the aircraft. For these symptoms, she had numerous admissions to hospital emergency departments and had received treatment for anaphylaxis and asthma with subcutaneous and intravenous adrenaline, corticosteroids, and bronchodilators. However, objective evidence of variable or reversible airflow limitation was never established. Two months earlier, she had had similar symptoms during a contrast-enhanced computed tomography scan of her abdomen to investigate a possible loin mass. On the basis of her previous history of anaphylaxis, she was given intravenous epinephrine and corticosteroids, shortly after which she experienced central chest tightness and nausea. Her electrocardiogram (ECG) (Fig 1, A) showed T-wave inversion in the inferior limb leads. Her troponin (15 ng/mL) and creatine kinase (284 IU; MB isoenzyme fraction, 42%) levels were raised. Findings of a coronary angiogram, a technetium Tc 99m sestamibi exercise perfusion scan, and an echocardiogram 5 days later were normal. Her chest radiograph and blood autoantibody profile findings were normal. She had regular symptoms of heartburn, acid regurgitation, and arthralgia and was taking levothyroxine for hypothyroidism. She had never smoked. We considered her symptoms to be consistent with laryngeal dysfunction (confirmed by direct laryngoscopy), hyperventilation, and gastroesophageal reflux. She was nonatopic (negative allergy skin prick test result and normal total serum IgE level) and had normal spirometry findings, ECG (Fig 1, B) findings, and cell counts in induced sputum. A methacholine inhalation test was performed by the tidal breathing method.1Immediately after inhalation of methacholine 16 mg/mL, she lost her voice and had central chest pain and sweating. The maximal inspiratory flow-volume curve (Fig 2) showed a variable extrathoracic obstructive pattern consistent with laryngeal dysfunction. Her ECG showed T-wave inversion in the inferior leads (Fig 1, C). Her end-tidal PCO2 was 39 mm Hg. Cardiac enzyme levels were not raised, and the pain was relieved with sublingual nitroglycerine. The PC20 (provocative concentration of agonist producing a 20% fall in FEV1) methacholine was 12 mg/mL, indicating borderline normal airway responsiveness. She was later assessed by a cardiologist, who confirmed the diagnosis of syndrome X and prescribed diltiazem, aspirin, and omeprazole. She has been told that she does not have asthma or allergies and is currently undergoing voice therapy and psychiatric counseling. An ECG repeated 2 weeks later showed normal findings (Fig 1, D).
B
C
D FIG 1. A, ECG showing T-wave inversion in leads III and aVF following the administration of intravenous epinephrine, associated with central chest pain and raised troponin. B, Normal ECG 5 days after the episode of chest pain. C, ECG showing T-wave inversion in leads III and aVF following the inhalation of methacholine (16 mg/mL). D, Normal ECG 2 weeks after the methacholine inhalation test.
This is the first report of angina and coronary spasm after methacholine inhalation. The case also illustrates the use of the methacholine inhalation test to identify laryngeal dysfunction as a cause of asthmalike symptoms. The methacholine inhalation test is generally a safe procedure without any serious adverse effects.2 Although subcutaneous administration of methacholine has been reported to cause angina in patients with Prinzmetal’s variant angina pectoris,3 this has not been reported after a bronchial provocation test. We can only speculate on the mechanism of angina in our patient, who had a coronary-prone behavior pattern, possible syndrome X, epinephrine-induced myocardial necrosis,4 and gastroesophageal reflux.5 Chest pain relieved with nitroglycerine and associated with reversible ischemic changes in the ECG and normal coronary artery anatomy suggests coronary vasospasm as the cause of chest pain.
Letters to the Editor 393
J ALLERGY CLIN IMMUNOL VOLUME 107, NUMBER 2
Krishnan Parameswaran, MDa Gerard Cox, MBChBa Allan Kitching, MDb Frederick Hargreave, MDa aAsthma Research Group bDivision of Cardiology Department of Medicine St Joseph’s Hospital and McMaster University 50 Charlton Ave E Hamilton, Ontario, L8N 4A6, Canada REFERENCES 1. Juniper EF, Cockcroft DW, Hargreave FE. Histamine and methacholine inhalation tests: a laboratory tidal breathing protocol. 2nd ed. Lund, Sweden: Astra Draco AB; 1994. 2. Parameswaran KN, Inman MD, Ekholm BP, Morris MM, Summers E, O’Byrne PM, et al. Protection against methacholine bronchoconstriction to assess relative potency of inhaled β2-agonist. Am J Respir Crit Care Med 1999;160:354-7. 3. Stang JM, Kolibash AJ, Schorling JB, Bush CA. Methacholine provocation of Prinzmetal’s variant angina pectoris: a revised perspective. Clin Cardiol 1982;5:393-402. 4. Ferry DR, Henry RL, Kern MJ. Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arteries. Am Heart J 1986;111:1193-5. 5. Mellow MH, Simpson AG, Watt L, Schoolmeester L, Haye OL. Esophageal acid perfusion in coronary artery disease: induction of myocardial ischemia. Gastroenterology 1983;85:306-12. 6. Christopher KL, Wood RP 2d, Eckert RC, Blager FB, Raney RA, Souhrada JF. Vocal-cord dysfunction presenting as asthma. N Engl J Med 1983;308:1566-70.
1/8/112267 doi:10.1067/mai.2001.112267
Food intolerance due to wine gums: Identification of copper chlorophyll (E141) as a possible pseudoallergen
FIG 2. Flow volume curves before and after inhalation of 16 mg/mL concentration of methacholine showing flow limitation during maximal inspiratory effort.
The role of laryngeal dysfunction in provoking angina is less clear. However, in this patient the recognition of the disorder during a methacholine inhalation test was important in counseling the patient that she did not have asthma. A proper evaluation of her spirometry on her numerous previous admissions may have detected this, and an earlier diagnosis may have prevented her from getting multiple injections of epinephrine and experiencing myocardial necrosis. Laryngeal dysfunction is a common cause of pseudoasthma6; however, the prevalence of the condition in suspected occupational asthma is not known.
To the Editor: Food intolerance is a commonly perceived problem in the general population and may lead to a variety of symptoms. We present a report of a young woman with relapsing angioedema, rhinoconjunctivitis, and asthma-like symptoms caused by exposure to copper chlorophyll (E141). A 28-year-old woman had a history of sudden facial swelling associated with asthma-like symptoms and rhinorrhea. She remembered having eaten in a Chinese restaurant and having consumed various alcoholic beverages including a cocktail and an herb-flavored liqueur on the day of her symptoms. She had a history of allergic rhinoconjunctivitis and atopic eczema in her childhood. She also recalled symptoms of an oropharyngeal allergy syndrome after eating carrots, nuts, and kiwifruit. Her physical examination findings were unremarkable. Routine blood test results were normal including concentration and activity of serum C1-esterase inhibitor. Skin prick test results were positive against anise, caraway, mugwort, celery, coriander, paprika, carrot, nuts, and kiwifruit. Her total serum IgE level was elevated to 676 kU/L. Allergen-specific IgE antibodies against various spices and herbs were found in her serum. Allergic angioedema and rhinitis were diagnosed. She was advised to avoid the suspected foods and beverages and instructed to keep a food diary. One month later she again had multiple episodes of acute eyelid swelling, dyspnea, and rhinoconjunctivitis. Her food diary revealed that she had consumed milk, rice, orange juice, cheese, bread, 2 alcoholic cocktails, and English wine gums (a jelly bean–like chewy, sweet confection of different colors and fruit flavors without a hard sugar coat) as possible triggers. An open challenge was per-