Elevated serum tryptase in exercise-induced anaphylaxis
1995; Elsevier BV; Volume: 95; Issue: 4 Linguagem: Inglês
10.1016/s0091-6749(95)70139-7
ISSN1097-6825
Autores Tópico(s)Allergic Rhinitis and Sensitization
ResumoExercise-induced anaphylaxis (EIA) is a unique medical emergency in that it derives from a physical allergy. 1Sheffer AL Austen KF Exercise-induced anaphylaxis.J ALLERGY C LIN IMMUNOL. 1980; 66: 106-111Abstract Full Text PDF PubMed Scopus (200) Google Scholar, 2Sheffer AL Soter NA McFadden ER et al.Exercise induced anaphylaxis: a distinct form of physical allergy.J ALLERGY CLIN IMMUNOL. 1983; 71: 311-316Abstract Full Text PDF PubMed Scopus (125) Google Scholar, 3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar Sheffer et al.2Sheffer AL Soter NA McFadden ER et al.Exercise induced anaphylaxis: a distinct form of physical allergy.J ALLERGY CLIN IMMUNOL. 1983; 71: 311-316Abstract Full Text PDF PubMed Scopus (125) Google Scholar believe EIA to be distinct from asthma, cholinergic urticaria, and angioedema, which can occur in some individuals who exercise. Several studies have suggested the role of mast cells in this disease3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar, 4Sheffer AL Tong AKF Murphy GF et al.Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation.J ALLERGY CLIN IMMUNOL. 1985; 75: 479-484Abstract Full Text PDF PubMed Scopus (110) Google Scholar as judged by biopsy and plasma histamine studies.The opportunity to evaluate a young man with EIA in whom striking elevation of serum tryptase was demonstrated during an acute episode recently arose and is described below.CASE REPORTK.Z., an 18-year-old male high school football player was seen in consultation; he was complaining of acute skin rashes and hives associated with exercise. He also stated that he could at times experience wheezing and dyspnea when the hives developed. However, not every outbreak of hives was associated with dyspnea, and at times, he noted that dyspnea could develop without hives. The hives could last up to 60 minutes after cessation of exercise, and dyspnea could last 30 to 45 minutes. This problem developed suddenly and recently, despite heavy athletic activity all through his teens. Exposure to temperature extremes could also cause symptoms. The level of exercise necessary to trigger an attack was not necessarily strenuous according to his experience. None of the attacks occurred after meals or snacks. The patient had no history of allergic disease from infancy to the present. He was a nonsmoker. The family history for atopic disease was negative. Results of physical examination were entirely normal. Results of allergy skin testing by the prick method were negative in response to a wide variety of inhalants including tree, grass, and weed pollens; fungi; pets; and house dust mite. Results of baseline spirometry were normal. The patient was asked to go jogging around the medical facility and to return to the office when he experienced any suggestive symptoms. He returned within 10 minutes, complaining of breathlessness, at which time physical examination revealed a blood pressure of 60/40 mm Hg, diffuse hives, angioedema, and wheezing. The hives were typical of urticaria rather than cholinergic in variety. Spirometry revealed airway obstruction (Table I). Blood samples were drawn for assay, and he was given 0.2 ml of subcutaneous epinephrine 1/1000 and nasal oxygen and was watched closely for the next 90 minutes during which he received another dose of 0.2 ml of epinephrine. All symptoms resolved, and physical findings returned to normal. Blood was drawn during the height of the attack and revealed leukocytosis and hemoconcentration (Table II). The serum tryptase level was elevated to 8 ng/ml (normal <1 ng/ml), and the plasma histamine level was elevated to 11 ng/ml (normal, 0 to 0.43 ng/ml).TABLE ISpirometric resultsPredictedBaselineAfter exercisePercent changeFVC (L)4.865.835.03−14FEV1 (L)4.194.983.44−31REF25-75 (L/sec)4.665.522.45−56FVC, Forced vital capacity; FEV1, forced expiratory volume in 1 second; FEF25-75, maximum mid-expiratory flow rate. Open table in a new tab TABLE IILaboratory valuesPatientsNormal rangeWBC count (cells/mm3)14,1003.5-11,000Hemoglobin (gm/dl)19.412.0-16.0Hematocrit (%)60.136-49Tryptase (ng/ml)8<1Histamine (ng/ml)110.-0.43WBC, White blood cell. Open table in a new tab After full recovery, the patient was advised regarding exercise curtailment and the use of autoinjectors of epinephrine, antihistamines, cromolyn sodium, and inhaled bronchodilators to deal with any symptoms that might develop when medical attention was not available. He has been followed up since this episode and has done well with this revised program of activity, without need for epinephrine. He has declined any further test challenges in which more detailed results could be obtained.DISCUSSIONThis case report clearly and dramatically demonstrates the role of mast cells in EIA. The elevated plasma histamine levels mirror those previously reported, and the elevated serum tryptase levels further document mast cell involvement in an attack triggered by mild exercise at a medical care facility. Elevations in plasma histamine have previously been reported.3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar, 5Lewis J Lieberman P Treadwell G et al.Exercise-induced urticaria, angioedema, and anaphylactoid episodes.J ALLERGY CLIN IMMUNOL. 1981; 68: 432-437Abstract Full Text PDF PubMed Scopus (53) Google Scholar, 6Silvers WS Exercise-induced allergies: the role of histamine release.Ann Allergy. 1992; 68: 58-63PubMed Google Scholar Furthermore, alterations in tissue mast cells in skin biopsy specimens of patients with EIA have been described. 4Sheffer AL Tong AKF Murphy GF et al.Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation.J ALLERGY CLIN IMMUNOL. 1985; 75: 479-484Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 7Sheffer AL Exercise-induced anaphylaxis.N Engl Regional Allergy Proc. 1988; 9: 215-217Crossref PubMed Scopus (7) Google Scholar A loss of electron density, loss of internal substructure of granules, and fusion of granule membranes with mast cell membranes—all of which were suggestive of mast cell activation—were noted in skin biopsy specimens of patients.7Sheffer AL Exercise-induced anaphylaxis.N Engl Regional Allergy Proc. 1988; 9: 215-217Crossref PubMed Scopus (7) Google ScholarIn this case, we had merely planned a mild exercise challenge to document the patient's history of exercise-induced urticaria. We had no reason to expect EIA or exercise-induced asthma. As a result, no control blood samples for histamine or tryptase determinations were obtained.Tryptase has been clearly shown to be a mediator of human mast cells and has been widely used as a marker of mast cell involvement in atopic patients with asthma and in patients with Hymenoptera venom–induced anaphylaxis.8Schwartz LB Tryptase, a mediator of human mast cells.J ALLERGY C LIN IMMUNOL. 1990; 86: 594-598Abstract Full Text PDF PubMed Scopus (113) Google Scholar, 9Yunginger JW Nelson DR Squillace DL et al.Laboratory investigation of deaths due to anaphylaxis.J Forensic Sci. 1991; 36: 857-865Crossref PubMed Google Scholar, 10Schwartz LB Metcalfe DD Miller JS et al.Tryptase levels as an indicator of mast cell activation in systemic anaphylaxis and mastocytosis.N Engl J Med. 1987; 316: 1622-1626Crossref PubMed Scopus (665) Google ScholarThis case report may be the first in vivo demonstration of tryptase involvement in EIA. The eventual development of more potent mast cell–stabilizing drugs may be of great clinical utility in preventing EIA episodes in patients subject to this disease. Furthermore, it would be of interest to assess other patients with exercise-induced asthma and anaphylaxis to evaluate the frequency with which these phenomena occur. Exercise-induced anaphylaxis (EIA) is a unique medical emergency in that it derives from a physical allergy. 1Sheffer AL Austen KF Exercise-induced anaphylaxis.J ALLERGY C LIN IMMUNOL. 1980; 66: 106-111Abstract Full Text PDF PubMed Scopus (200) Google Scholar, 2Sheffer AL Soter NA McFadden ER et al.Exercise induced anaphylaxis: a distinct form of physical allergy.J ALLERGY CLIN IMMUNOL. 1983; 71: 311-316Abstract Full Text PDF PubMed Scopus (125) Google Scholar, 3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar Sheffer et al.2Sheffer AL Soter NA McFadden ER et al.Exercise induced anaphylaxis: a distinct form of physical allergy.J ALLERGY CLIN IMMUNOL. 1983; 71: 311-316Abstract Full Text PDF PubMed Scopus (125) Google Scholar believe EIA to be distinct from asthma, cholinergic urticaria, and angioedema, which can occur in some individuals who exercise. Several studies have suggested the role of mast cells in this disease3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar, 4Sheffer AL Tong AKF Murphy GF et al.Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation.J ALLERGY CLIN IMMUNOL. 1985; 75: 479-484Abstract Full Text PDF PubMed Scopus (110) Google Scholar as judged by biopsy and plasma histamine studies. The opportunity to evaluate a young man with EIA in whom striking elevation of serum tryptase was demonstrated during an acute episode recently arose and is described below. CASE REPORTK.Z., an 18-year-old male high school football player was seen in consultation; he was complaining of acute skin rashes and hives associated with exercise. He also stated that he could at times experience wheezing and dyspnea when the hives developed. However, not every outbreak of hives was associated with dyspnea, and at times, he noted that dyspnea could develop without hives. The hives could last up to 60 minutes after cessation of exercise, and dyspnea could last 30 to 45 minutes. This problem developed suddenly and recently, despite heavy athletic activity all through his teens. Exposure to temperature extremes could also cause symptoms. The level of exercise necessary to trigger an attack was not necessarily strenuous according to his experience. None of the attacks occurred after meals or snacks. The patient had no history of allergic disease from infancy to the present. He was a nonsmoker. The family history for atopic disease was negative. Results of physical examination were entirely normal. Results of allergy skin testing by the prick method were negative in response to a wide variety of inhalants including tree, grass, and weed pollens; fungi; pets; and house dust mite. Results of baseline spirometry were normal. The patient was asked to go jogging around the medical facility and to return to the office when he experienced any suggestive symptoms. He returned within 10 minutes, complaining of breathlessness, at which time physical examination revealed a blood pressure of 60/40 mm Hg, diffuse hives, angioedema, and wheezing. The hives were typical of urticaria rather than cholinergic in variety. Spirometry revealed airway obstruction (Table I). Blood samples were drawn for assay, and he was given 0.2 ml of subcutaneous epinephrine 1/1000 and nasal oxygen and was watched closely for the next 90 minutes during which he received another dose of 0.2 ml of epinephrine. All symptoms resolved, and physical findings returned to normal. Blood was drawn during the height of the attack and revealed leukocytosis and hemoconcentration (Table II). The serum tryptase level was elevated to 8 ng/ml (normal <1 ng/ml), and the plasma histamine level was elevated to 11 ng/ml (normal, 0 to 0.43 ng/ml).TABLE ISpirometric resultsPredictedBaselineAfter exercisePercent changeFVC (L)4.865.835.03−14FEV1 (L)4.194.983.44−31REF25-75 (L/sec)4.665.522.45−56FVC, Forced vital capacity; FEV1, forced expiratory volume in 1 second; FEF25-75, maximum mid-expiratory flow rate. Open table in a new tab TABLE IILaboratory valuesPatientsNormal rangeWBC count (cells/mm3)14,1003.5-11,000Hemoglobin (gm/dl)19.412.0-16.0Hematocrit (%)60.136-49Tryptase (ng/ml)8<1Histamine (ng/ml)110.-0.43WBC, White blood cell. Open table in a new tab After full recovery, the patient was advised regarding exercise curtailment and the use of autoinjectors of epinephrine, antihistamines, cromolyn sodium, and inhaled bronchodilators to deal with any symptoms that might develop when medical attention was not available. He has been followed up since this episode and has done well with this revised program of activity, without need for epinephrine. He has declined any further test challenges in which more detailed results could be obtained. K.Z., an 18-year-old male high school football player was seen in consultation; he was complaining of acute skin rashes and hives associated with exercise. He also stated that he could at times experience wheezing and dyspnea when the hives developed. However, not every outbreak of hives was associated with dyspnea, and at times, he noted that dyspnea could develop without hives. The hives could last up to 60 minutes after cessation of exercise, and dyspnea could last 30 to 45 minutes. This problem developed suddenly and recently, despite heavy athletic activity all through his teens. Exposure to temperature extremes could also cause symptoms. The level of exercise necessary to trigger an attack was not necessarily strenuous according to his experience. None of the attacks occurred after meals or snacks. The patient had no history of allergic disease from infancy to the present. He was a nonsmoker. The family history for atopic disease was negative. Results of physical examination were entirely normal. Results of allergy skin testing by the prick method were negative in response to a wide variety of inhalants including tree, grass, and weed pollens; fungi; pets; and house dust mite. Results of baseline spirometry were normal. The patient was asked to go jogging around the medical facility and to return to the office when he experienced any suggestive symptoms. He returned within 10 minutes, complaining of breathlessness, at which time physical examination revealed a blood pressure of 60/40 mm Hg, diffuse hives, angioedema, and wheezing. The hives were typical of urticaria rather than cholinergic in variety. Spirometry revealed airway obstruction (Table I). Blood samples were drawn for assay, and he was given 0.2 ml of subcutaneous epinephrine 1/1000 and nasal oxygen and was watched closely for the next 90 minutes during which he received another dose of 0.2 ml of epinephrine. All symptoms resolved, and physical findings returned to normal. Blood was drawn during the height of the attack and revealed leukocytosis and hemoconcentration (Table II). The serum tryptase level was elevated to 8 ng/ml (normal <1 ng/ml), and the plasma histamine level was elevated to 11 ng/ml (normal, 0 to 0.43 ng/ml). FVC, Forced vital capacity; FEV1, forced expiratory volume in 1 second; FEF25-75, maximum mid-expiratory flow rate. WBC, White blood cell. After full recovery, the patient was advised regarding exercise curtailment and the use of autoinjectors of epinephrine, antihistamines, cromolyn sodium, and inhaled bronchodilators to deal with any symptoms that might develop when medical attention was not available. He has been followed up since this episode and has done well with this revised program of activity, without need for epinephrine. He has declined any further test challenges in which more detailed results could be obtained. DISCUSSIONThis case report clearly and dramatically demonstrates the role of mast cells in EIA. The elevated plasma histamine levels mirror those previously reported, and the elevated serum tryptase levels further document mast cell involvement in an attack triggered by mild exercise at a medical care facility. Elevations in plasma histamine have previously been reported.3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar, 5Lewis J Lieberman P Treadwell G et al.Exercise-induced urticaria, angioedema, and anaphylactoid episodes.J ALLERGY CLIN IMMUNOL. 1981; 68: 432-437Abstract Full Text PDF PubMed Scopus (53) Google Scholar, 6Silvers WS Exercise-induced allergies: the role of histamine release.Ann Allergy. 1992; 68: 58-63PubMed Google Scholar Furthermore, alterations in tissue mast cells in skin biopsy specimens of patients with EIA have been described. 4Sheffer AL Tong AKF Murphy GF et al.Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation.J ALLERGY CLIN IMMUNOL. 1985; 75: 479-484Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 7Sheffer AL Exercise-induced anaphylaxis.N Engl Regional Allergy Proc. 1988; 9: 215-217Crossref PubMed Scopus (7) Google Scholar A loss of electron density, loss of internal substructure of granules, and fusion of granule membranes with mast cell membranes—all of which were suggestive of mast cell activation—were noted in skin biopsy specimens of patients.7Sheffer AL Exercise-induced anaphylaxis.N Engl Regional Allergy Proc. 1988; 9: 215-217Crossref PubMed Scopus (7) Google ScholarIn this case, we had merely planned a mild exercise challenge to document the patient's history of exercise-induced urticaria. We had no reason to expect EIA or exercise-induced asthma. As a result, no control blood samples for histamine or tryptase determinations were obtained.Tryptase has been clearly shown to be a mediator of human mast cells and has been widely used as a marker of mast cell involvement in atopic patients with asthma and in patients with Hymenoptera venom–induced anaphylaxis.8Schwartz LB Tryptase, a mediator of human mast cells.J ALLERGY C LIN IMMUNOL. 1990; 86: 594-598Abstract Full Text PDF PubMed Scopus (113) Google Scholar, 9Yunginger JW Nelson DR Squillace DL et al.Laboratory investigation of deaths due to anaphylaxis.J Forensic Sci. 1991; 36: 857-865Crossref PubMed Google Scholar, 10Schwartz LB Metcalfe DD Miller JS et al.Tryptase levels as an indicator of mast cell activation in systemic anaphylaxis and mastocytosis.N Engl J Med. 1987; 316: 1622-1626Crossref PubMed Scopus (665) Google ScholarThis case report may be the first in vivo demonstration of tryptase involvement in EIA. The eventual development of more potent mast cell–stabilizing drugs may be of great clinical utility in preventing EIA episodes in patients subject to this disease. Furthermore, it would be of interest to assess other patients with exercise-induced asthma and anaphylaxis to evaluate the frequency with which these phenomena occur. This case report clearly and dramatically demonstrates the role of mast cells in EIA. The elevated plasma histamine levels mirror those previously reported, and the elevated serum tryptase levels further document mast cell involvement in an attack triggered by mild exercise at a medical care facility. Elevations in plasma histamine have previously been reported.3Casale TB Keahey TM Kaliner M Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.JAMA. 1986; 255: 2049-2053Crossref PubMed Scopus (73) Google Scholar, 5Lewis J Lieberman P Treadwell G et al.Exercise-induced urticaria, angioedema, and anaphylactoid episodes.J ALLERGY CLIN IMMUNOL. 1981; 68: 432-437Abstract Full Text PDF PubMed Scopus (53) Google Scholar, 6Silvers WS Exercise-induced allergies: the role of histamine release.Ann Allergy. 1992; 68: 58-63PubMed Google Scholar Furthermore, alterations in tissue mast cells in skin biopsy specimens of patients with EIA have been described. 4Sheffer AL Tong AKF Murphy GF et al.Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation.J ALLERGY CLIN IMMUNOL. 1985; 75: 479-484Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 7Sheffer AL Exercise-induced anaphylaxis.N Engl Regional Allergy Proc. 1988; 9: 215-217Crossref PubMed Scopus (7) Google Scholar A loss of electron density, loss of internal substructure of granules, and fusion of granule membranes with mast cell membranes—all of which were suggestive of mast cell activation—were noted in skin biopsy specimens of patients.7Sheffer AL Exercise-induced anaphylaxis.N Engl Regional Allergy Proc. 1988; 9: 215-217Crossref PubMed Scopus (7) Google Scholar In this case, we had merely planned a mild exercise challenge to document the patient's history of exercise-induced urticaria. We had no reason to expect EIA or exercise-induced asthma. As a result, no control blood samples for histamine or tryptase determinations were obtained. Tryptase has been clearly shown to be a mediator of human mast cells and has been widely used as a marker of mast cell involvement in atopic patients with asthma and in patients with Hymenoptera venom–induced anaphylaxis.8Schwartz LB Tryptase, a mediator of human mast cells.J ALLERGY C LIN IMMUNOL. 1990; 86: 594-598Abstract Full Text PDF PubMed Scopus (113) Google Scholar, 9Yunginger JW Nelson DR Squillace DL et al.Laboratory investigation of deaths due to anaphylaxis.J Forensic Sci. 1991; 36: 857-865Crossref PubMed Google Scholar, 10Schwartz LB Metcalfe DD Miller JS et al.Tryptase levels as an indicator of mast cell activation in systemic anaphylaxis and mastocytosis.N Engl J Med. 1987; 316: 1622-1626Crossref PubMed Scopus (665) Google Scholar This case report may be the first in vivo demonstration of tryptase involvement in EIA. The eventual development of more potent mast cell–stabilizing drugs may be of great clinical utility in preventing EIA episodes in patients subject to this disease. Furthermore, it would be of interest to assess other patients with exercise-induced asthma and anaphylaxis to evaluate the frequency with which these phenomena occur.
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