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Thrombolytic treatment of acute pulmonary embolism in myotonic dystrophy
220
Letters to the Editor
junction. In the third patient, the biopsy revealed a leukocytic vasculitis but an immunofluorescence study was not carried out. In the third case, hepatitis was cholestatic. Chemli et al. reported the fourth patient with HSP associated with HAV infection (5). Both third and fourth patients had cholestatic hepatitis characterized with elevated bilirubin levels despite a decrease in transaminase levels. Our case did not show such a cholestatic presentation. The College of Rheumatology published diagnostic criteria for HSP as palpable purpura, age less than 20 years at disease onset, bowel angina, and wall granulocytes on biopsy (8). The presence of any two or more criteria yields a sensitivity of 87.1% and specificity of 87.7% (8). Despite the lack of cutaneous biopsy, our case met three of these criteria (palpable purpura, age less than 20 years at disease onset, and bowel angina). In conclusion, although this is a rare association, we emphasize that in children with HSP presenting with elevated transaminase levels, hepatitis A should be investigated, especially in developing countries where hepatitis A is common. Sevin Altınkaynak, MD Vildan Ertekin M. Ays¸e Selimogˇlu Department of Pediatrics Faculty of Medicine Atatürk University Erzurum, Turkey doi:10.1016/j.jemermed.2005.12.011
REFERENCES 1. Tizard EJ. Henoch-Schoenlein purpura. Arch Dis Child 1999;80: 380 –3. 2. Bozaykut A, Atay E, Atay Z, Ipek IO, Akin M, Dursun E. Acute infantile haemorrhagic oedema associated with hepatitis A. Ann Trop Paediatr 2002;22:59 – 61. 3. Islek I, Kalayci AG, Gok F, Muslu A. Henoch-Schonlein purpura associated with hepatitis A infection. Pediatr Int 2003;45:114 – 6. 4. Garty BZ, Danon YL, Nitzan M. Schoenlein-Henoch purpura associated with hepatitis A infection. Am J Dis Child 1985;139:547. 5. Chemli J, Zouari N, Belkadhi A, Abroug S, Harbi A. Hepatitis A infection and Henoch-Schonlein purpura: a rare association. Arch Pediatr 2004;11:1202– 4. 6. Schiff ER. Atypical clinical manifestations of hepatitis A. Vaccine 1992;10(Suppl 1):S18 –20. 7. Press J, Maslovitz S, Avinoach I. Cutaneous necrotizing vasculitis associated with hepatitis A virus infection. J Rheumatol 1997;24: 965–7. 8. Mills JA, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schonlein purpura. Arthritis Rheum 1990;33:1114 –21.
e THROMBOLYTIC TREATMENT OF ACUTE PULMONARY EMBOLISM IN MYOTONIC DYSTROPHY e To the Editor: A 48-year-old man with myotonic/muscular dystrophy, diagnosed 10 years prior, who was wheelchair bound, presented with sudden onset of shortness of breath and progressive swelling and pain of the left leg for 3 days. On physical examination, he had respiratory distress, tachycardia, and an oxygen saturation of 92%. Blood pressure was 140/70 mm Hg, and the heart rate was 90 beats/min. There was a mild ptosis and bilateral cataracts. Chest examination revealed a prolonged expiratory phase, and bilateral basilar rhonchi. The left leg was swollen and tender, and Homan’s sign was positive. The testicles were atrophic. The thenar muscles were atrophic and myotonic, and the hand grasp was weak bilaterally. Proximal and distal muscles were also weak in the lower extremities. Deep tendon reflexes were diminished. Arterial blood gases showed pH 7.39, pCO2 57 mm Hg, and pO2 55 mm Hg (2 years prior, pO2 was 75 mm Hg). A chest X-ray study showed right atrial enlargement. Spiral computed angiogram revealed filling defects in the left descending pulmonary artery and right upper lobe pulmonary artery highly suggestive of pulmonary embolism (Figure 1). The patient was started initially on intravenous heparin bolus but later thrombolytic therapy with alteplase (t-PA), 100 mg intravenously over 2 h, was given with marked improvement of symptoms. Repeated spiral CT angiography showed resolution of the filling defects (Figure 2). Muscular dystrophies are inherited progressive myopathic disorders. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two prototypes of muscular dystrophies caused by mutations of dystrophin gene. Normally, dystrophin is a protein re-
Figure 1. Spiral CT angiogram shows filling defects in the left descending pulmonary artery and right upper lobe pulmonary artery.
The Journal of Emergency Medicine
Figure 2. Spiral CT angiography shows resolution of the pulmonary arteries filling defects after treatment with thrombolytics.
quired for stabilization of the plasma membrane of muscle fibers, but in muscular dystrophies it is abnormal or absent, leading to degeneration of muscle fibers and progressive muscle weakness. In general, these dystrophies are associated with a hypercoagulable state and higher risk of pulmonary thrombosis. Up to 96% of DMD patients have abnormal markers of coagulation and fibrinolysis (1). There other factors that can explain this predisposition to thrombosis. First, these patients are more sedentary and some are wheelchair or bed bound. Second, the elevation of serum creatinine kinase (CK) and lactate dehydrogenase (LDH) due to muscle fiber necrosis may increase the risk of thrombosis (2). Third, in some patients with benign forms of muscular dystrophies and recurrent thrombosis, there may be upregulation of utrophin (a homolog of dystrophin) to prevent the muscle wasting in the dystrophin deficient BMD or DMD. This upregulation of utrophin may influence the coagulation system (3). Also, in these patients, the muscle cell membranes may have a lower expression of thrombomodulin compared to other forms of BMD or DMD with less frequent thrombosis epsiodes (1). Pulmonary embolism (PE) is a common cause of hospital deaths. The most important factor affecting mortality is shock due to right heart failure secondary to massive PE. Most patients die within the first few hours of the event (4). Therefore, it is important to start treatment as soon as possible. The standard regimen is anticoagulation with heparin (unfractionated or low molecular weight) and early oral warfarin in stable patients. In
221
some situations, thrombolytic therapy is indicated. Thrombolytics activate plasminogen to form plasmin that results in fibrinolysis, a process that anticoagulants cannot do. Indications of thrombolytics include hemodynamically significant PE associated with hypotension, severely compromised oxygenation, or right ventricular (RV) failure or dilatation by echocardiogram in the absence of chronic obstructive lung disease or other causes of RV failure (5). In these patients, accelerated lysis of PE using thrombolytics is indicated. Stable patients with a major embolic load such as obstruction of blood flow to a lobe or multiple lung segments may be given thrombolytic therapy in the absence of absolute or relative contradictions (5). It is important before initiating this kind of therapy to confirm PE with high probability V/Q scan, by angiogram or by a spiral computed tomography (CT) scan. Our patient was diagnosed with massive PE based on clinical presentation. He did not have hypotension, but we elected to administer thrombolytic therapy because PE involved multiple lung segments by spiral CT, oxygenation was compromised, and the chest X-ray study showed right atrial enlargement. Although this is a single case, we find no reason to withhold thrombolytic therapy in a patient with muscular dystrophy. We recommend that physicians search for PE in these patients and use thrombolytics whenever indicated. Fadi I Jabr, MD Health Associates of Peace Harbor Florence, Oregon doi:10.1016/j.jemermed.2005.12.012
REFERENCES 1. Saito Y, Komiya T, Kawai M. Hypercoagulabe state in Duchenne muscular dystrophy. Rinsho Shinkeiagaku 1997;37:74 – 8. 2. Nakayama T, Saito Y, Uchiyama T, Yatabe K, Kawai M. Pathogenesis of pulmonary thrombosis in Duchenne muscular dystropy; a consideration from changes in serum CK and LDH levels. Rinsho Shinkeiagaku 2000;40:55– 8. 3. Higuchi I, Niiyama T, Uchida Y, et al. Multiple episodes of thrombosis in a patient with Becker muscular dystrophy with marked expression of utrophim on the muscle cell membrane. Acta Neuropathol 1999;98:313– 6. 4. Alpert JS, Smith R, Carlson J, Ockene IS, Dexter L, Dalen JE. Mortality in patients treated for pulmonary embolism. JAMA 1976; 236:1477– 80. 5. Thrombolytic therapy in thrombosis: a National Institutes of Health consensus development conference. Ann Intern Med 1980;93:141.
Letters to the Editor
junction. In the third patient, the biopsy revealed a leukocytic vasculitis but an immunofluorescence study was not carried out. In the third case, hepatitis was cholestatic. Chemli et al. reported the fourth patient with HSP associated with HAV infection (5). Both third and fourth patients had cholestatic hepatitis characterized with elevated bilirubin levels despite a decrease in transaminase levels. Our case did not show such a cholestatic presentation. The College of Rheumatology published diagnostic criteria for HSP as palpable purpura, age less than 20 years at disease onset, bowel angina, and wall granulocytes on biopsy (8). The presence of any two or more criteria yields a sensitivity of 87.1% and specificity of 87.7% (8). Despite the lack of cutaneous biopsy, our case met three of these criteria (palpable purpura, age less than 20 years at disease onset, and bowel angina). In conclusion, although this is a rare association, we emphasize that in children with HSP presenting with elevated transaminase levels, hepatitis A should be investigated, especially in developing countries where hepatitis A is common. Sevin Altınkaynak, MD Vildan Ertekin M. Ays¸e Selimogˇlu Department of Pediatrics Faculty of Medicine Atatürk University Erzurum, Turkey doi:10.1016/j.jemermed.2005.12.011
REFERENCES 1. Tizard EJ. Henoch-Schoenlein purpura. Arch Dis Child 1999;80: 380 –3. 2. Bozaykut A, Atay E, Atay Z, Ipek IO, Akin M, Dursun E. Acute infantile haemorrhagic oedema associated with hepatitis A. Ann Trop Paediatr 2002;22:59 – 61. 3. Islek I, Kalayci AG, Gok F, Muslu A. Henoch-Schonlein purpura associated with hepatitis A infection. Pediatr Int 2003;45:114 – 6. 4. Garty BZ, Danon YL, Nitzan M. Schoenlein-Henoch purpura associated with hepatitis A infection. Am J Dis Child 1985;139:547. 5. Chemli J, Zouari N, Belkadhi A, Abroug S, Harbi A. Hepatitis A infection and Henoch-Schonlein purpura: a rare association. Arch Pediatr 2004;11:1202– 4. 6. Schiff ER. Atypical clinical manifestations of hepatitis A. Vaccine 1992;10(Suppl 1):S18 –20. 7. Press J, Maslovitz S, Avinoach I. Cutaneous necrotizing vasculitis associated with hepatitis A virus infection. J Rheumatol 1997;24: 965–7. 8. Mills JA, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schonlein purpura. Arthritis Rheum 1990;33:1114 –21.
e THROMBOLYTIC TREATMENT OF ACUTE PULMONARY EMBOLISM IN MYOTONIC DYSTROPHY e To the Editor: A 48-year-old man with myotonic/muscular dystrophy, diagnosed 10 years prior, who was wheelchair bound, presented with sudden onset of shortness of breath and progressive swelling and pain of the left leg for 3 days. On physical examination, he had respiratory distress, tachycardia, and an oxygen saturation of 92%. Blood pressure was 140/70 mm Hg, and the heart rate was 90 beats/min. There was a mild ptosis and bilateral cataracts. Chest examination revealed a prolonged expiratory phase, and bilateral basilar rhonchi. The left leg was swollen and tender, and Homan’s sign was positive. The testicles were atrophic. The thenar muscles were atrophic and myotonic, and the hand grasp was weak bilaterally. Proximal and distal muscles were also weak in the lower extremities. Deep tendon reflexes were diminished. Arterial blood gases showed pH 7.39, pCO2 57 mm Hg, and pO2 55 mm Hg (2 years prior, pO2 was 75 mm Hg). A chest X-ray study showed right atrial enlargement. Spiral computed angiogram revealed filling defects in the left descending pulmonary artery and right upper lobe pulmonary artery highly suggestive of pulmonary embolism (Figure 1). The patient was started initially on intravenous heparin bolus but later thrombolytic therapy with alteplase (t-PA), 100 mg intravenously over 2 h, was given with marked improvement of symptoms. Repeated spiral CT angiography showed resolution of the filling defects (Figure 2). Muscular dystrophies are inherited progressive myopathic disorders. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two prototypes of muscular dystrophies caused by mutations of dystrophin gene. Normally, dystrophin is a protein re-
Figure 1. Spiral CT angiogram shows filling defects in the left descending pulmonary artery and right upper lobe pulmonary artery.
The Journal of Emergency Medicine
Figure 2. Spiral CT angiography shows resolution of the pulmonary arteries filling defects after treatment with thrombolytics.
quired for stabilization of the plasma membrane of muscle fibers, but in muscular dystrophies it is abnormal or absent, leading to degeneration of muscle fibers and progressive muscle weakness. In general, these dystrophies are associated with a hypercoagulable state and higher risk of pulmonary thrombosis. Up to 96% of DMD patients have abnormal markers of coagulation and fibrinolysis (1). There other factors that can explain this predisposition to thrombosis. First, these patients are more sedentary and some are wheelchair or bed bound. Second, the elevation of serum creatinine kinase (CK) and lactate dehydrogenase (LDH) due to muscle fiber necrosis may increase the risk of thrombosis (2). Third, in some patients with benign forms of muscular dystrophies and recurrent thrombosis, there may be upregulation of utrophin (a homolog of dystrophin) to prevent the muscle wasting in the dystrophin deficient BMD or DMD. This upregulation of utrophin may influence the coagulation system (3). Also, in these patients, the muscle cell membranes may have a lower expression of thrombomodulin compared to other forms of BMD or DMD with less frequent thrombosis epsiodes (1). Pulmonary embolism (PE) is a common cause of hospital deaths. The most important factor affecting mortality is shock due to right heart failure secondary to massive PE. Most patients die within the first few hours of the event (4). Therefore, it is important to start treatment as soon as possible. The standard regimen is anticoagulation with heparin (unfractionated or low molecular weight) and early oral warfarin in stable patients. In
221
some situations, thrombolytic therapy is indicated. Thrombolytics activate plasminogen to form plasmin that results in fibrinolysis, a process that anticoagulants cannot do. Indications of thrombolytics include hemodynamically significant PE associated with hypotension, severely compromised oxygenation, or right ventricular (RV) failure or dilatation by echocardiogram in the absence of chronic obstructive lung disease or other causes of RV failure (5). In these patients, accelerated lysis of PE using thrombolytics is indicated. Stable patients with a major embolic load such as obstruction of blood flow to a lobe or multiple lung segments may be given thrombolytic therapy in the absence of absolute or relative contradictions (5). It is important before initiating this kind of therapy to confirm PE with high probability V/Q scan, by angiogram or by a spiral computed tomography (CT) scan. Our patient was diagnosed with massive PE based on clinical presentation. He did not have hypotension, but we elected to administer thrombolytic therapy because PE involved multiple lung segments by spiral CT, oxygenation was compromised, and the chest X-ray study showed right atrial enlargement. Although this is a single case, we find no reason to withhold thrombolytic therapy in a patient with muscular dystrophy. We recommend that physicians search for PE in these patients and use thrombolytics whenever indicated. Fadi I Jabr, MD Health Associates of Peace Harbor Florence, Oregon doi:10.1016/j.jemermed.2005.12.012
REFERENCES 1. Saito Y, Komiya T, Kawai M. Hypercoagulabe state in Duchenne muscular dystrophy. Rinsho Shinkeiagaku 1997;37:74 – 8. 2. Nakayama T, Saito Y, Uchiyama T, Yatabe K, Kawai M. Pathogenesis of pulmonary thrombosis in Duchenne muscular dystropy; a consideration from changes in serum CK and LDH levels. Rinsho Shinkeiagaku 2000;40:55– 8. 3. Higuchi I, Niiyama T, Uchida Y, et al. Multiple episodes of thrombosis in a patient with Becker muscular dystrophy with marked expression of utrophim on the muscle cell membrane. Acta Neuropathol 1999;98:313– 6. 4. Alpert JS, Smith R, Carlson J, Ockene IS, Dexter L, Dalen JE. Mortality in patients treated for pulmonary embolism. JAMA 1976; 236:1477– 80. 5. Thrombolytic therapy in thrombosis: a National Institutes of Health consensus development conference. Ann Intern Med 1980;93:141.