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A 39-Year-Old Postpartum Woman With Foot Drop and Shortness of Breath
[
Pulmonary, Critical Care, and Sleep Pearls
]
A 39-Year-Old Postpartum Woman With Foot Drop and Shortness of Breath Atul K. Mehta, MD; Carol A. Langford, MD, MHS; David O. Taylor, MD; Michael Bolen, MD; and Anita J. Reddy, MD
A 39-year-old white woman with a history of adult-onset asthma, chronic sinusitis, and nasal polyposis presented to the ED with dyspnea and left lower extremity weakness and pain. Three months prior to her presentation she had an uncomplicated delivery of her second child, but during her pregnancy she experienced increasing asthma symptoms and nasal congestion. These symptoms progressed after delivery despite treatment with albuterol inhalers and antibiotics.
Physical Examination Findings Vitals signs on presentation were as follows: BP, 105/73 mm Hg; heart rate, 120 beats/min; respiratory rate, 18 breaths/min; oxygen saturation, 94% on room air (but she soon required supplemental oxygen); and temperature, 37.1 C. Pulmonary examination revealed bilateral rales. Cardiac examination revealed jugular venous distension, sinus tachycardia, and no S3 or S4. Musculoskeletal examination was normal. Neurologic examination showed intact cranial nerves, intact strength except for inability to dorsiflex or plantarflex the left foot, left lower extremity hyperalgesia, and decreased sensation of the lateral and dorsal aspects of the left foot.
Diagnostic Studies Pertinent laboratory data included the following (peak values): WBC count, 13.3 k/mL with 53% eosinophils; C-reactive protein, 19.9 mg/dL; erythrocyte sedimentation rate, 45 mm/h; creatine kinase,
AFFILIATIONS: From the Department of Internal Medicine (Dr Mehta), the Center for Vasculitis Care and Research (Dr Langford), Department of Rheumatic and Immunologic Diseases, the Department of Cardiovascular Medicine (Dr Taylor), the Imaging Institute (Dr Bolen), Cardiovascular Section, and the Respiratory Institute (Dr Reddy), Cleveland Clinic Foundation, Cleveland, OH.
journal.publications.chestnet.org
CHEST 2016; 149(2):e61–e64
1,240 U/L; myocardial band fraction, 65 ng/mL; troponin T, 4.35 ng/mL; N-terminal-pro brain natriuretic peptide, 6,883 pg/mL; and serum creatinine, 0.71. Urinalysis was normal. Chest CT scan displayed bilateral lung consolidations with pleural and pericardial effusions. MRI of the brain revealed frontal and parietal lobe punctate foci. ECG showed possible acute anterolateral infarct. Echocardiography demonstrated an ejection fraction (EF) of 25% with nearly the entire left ventricle exhibiting hypokinesis. The right ventricle had preserved function. Cardiac angiography revealed normal epicardial coronary arteries, but rightsided heart catheterization revealed elevated filling pressures. Cardiac MRI showed areas of myocarditis vs myocardial fibrosis (Fig 1). Additional laboratory results included negative antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCAs).
CORRESPONDENCE TO: Atul K. Mehta, MD, Internal Medicine Residency Program, Cleveland Clinic, 9500 Euclid Ave, NA10, Cleveland, OH 44114; e-mail: [email protected] Copyright Ó 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2015.10.051
e61
Figure 1 – Images from cardiac MRI with contrast. A, Mid- and basal-lung consolidations (*). B, Abnormal low signal along the left border of the interventricular septum (top arrow), bilateral pleural effusions (X), and a small pericardial effusion (lower arrow). C and D, Again, an abnormal low signal along the left border of the interventricular septum (black arrows) and an abnormal bright signal along the right side of the interventricular septum (white arrows). The overall imaging findings suggest endomyocarditis with mild adjacent laminar thrombus. (Reprinted with permission from Michael Bolen, MD.)
What is the diagnosis?
e62 Pulmonary, Critical Care, and Sleep Pearls
[
149#2 CHEST FEBRUARY 2016
]
Diagnosis: Eosinophilic granulomatosis with polyangiitis, with cardiac and neurologic involvement Discussion Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss) is an uncommon, potentially fatal, primary systemic vasculitis. It often affects patients between the ages of 40 and 60 years old, with an annual incidence of 2.4 people per million. EGPA is defined by eosinophil-rich and necrotizing granulomatous inflammation (often involving the respiratory tract) and necrotizing vasculitis predominantly affecting small to medium vessels. The clinical features are thought of as having three phases: an allergic phase (asthma, nasal polyps, rhinosinusitis), an eosinophilic phase (peripheral and tissue eosinophilia), and a vasculitic phase (nerve, skin, lung, kidney, GI tract, and heart). Although these phases may not be sequential, the median time from asthma symptoms to necrotizing vasculitis is 3 to 4 years. To date, there are no established diagnostic criteria for EGPA; the diagnosis is based on the constellation of clinical findings and the exclusion of other possible causes. Although an association between EGPA and antimyeloperoxidase-/peri-nuclear ANCA exists, only about 40% of patients with EGPA are ANCA positive. Some studies have found ANCA-positive EGPA to be associated with glomerulonephritis, whereas patients who are ANCA negative more commonly have cardiac involvement. EGPA has a wide range of cardiac manifestations and can affect multiple cardiac structures (Table 1). ECG changes can be nonspecific. Echocardiography should be performed on all patients presenting with EGPA and TABLE 1
] Possible Cardiac Manifestations of EGPA
Manifestation
can show pericardial effusion or ventricular dysfunction. If heart involvement is suspected, cardiac MRI can provide detailed imaging of the pericardium and the myocardium supporting the presence of inflammation and/or fibrosis. Cardiac involvement has been reported in 15% to 52% of patients with EGPA and is responsible for approximately 39% of mortality, making it an important manifestation in this population. Treatment of EGPA is based on disease severity. Systemic glucocorticoids represent the foundation of treatment regimens and may be the only required therapy for patients with nonsevere disease. For patients with organ- or life-threatening features, specifically cardiac disease, combined treatment with glucocorticoids and cyclophosphamide (CYC) has improved patient outcomes. With this approach, glucocorticoids are tapered slowly, and CYC is replaced after 3 to 6 months by less toxic medications (azathioprine, methotrexate) for maintenance therapy. It is unknown whether pregnancy impacts EGPA disease activity, including initial diagnosis or relapse. Because of its rarity, there are few reported cases describing pregnancy and the postpartum period in women with quiescent or active EGPA. In the available reports of those who had active EGPA, all treatment regimens included glucocorticoids, with disease severity and pregnancy trimester influencing the use of other immunosuppressive agents. CYC, methotrexate, and mycophenolate mofetil are all contraindicated during pregnancy, although azathioprine has been used during pregnancy after careful assessment of the relative risks and benefits. Prognosis of both mother and fetus depend on the degree of organ involvement, with cardiac involvement having the worst outcomes. Women with EGPA who become pregnant should be followed by a high-risk obstetrician and the physician managing their EGPA. Close monitoring should continue during the immediate postpartum period for emergence of disease activity.
Pericarditis
Clinical Course
Myocarditis
The patient had clinical features consistent with EGPA, including worsening of adult-onset asthma symptoms, sinus disease with polyposis, peripheral eosinophilia, motor and sensory mononeuritis multiplex, pulmonary infiltrates, possible CNS involvement by brain imaging, and nonischemic cardiomyopathy. Hypereosinophilic syndrome was considered another diagnostic possibility for the case because it can present similarly to EGPA with multiorgan eosinophilic injury but it is not
Acute coronary syndrome Arrhythmias (ie, atrioventricular block, ventricular arrhythmias) Congestive heart failure Valvular heart disease (mitral valve regurgitation, aortic valve regurgitation) Sudden death EGPA ¼ eosinophilic granulomatosis with polyangiitis.
journal.publications.chestnet.org
e63
associated with vasculitis. Postpartum cardiomyopathy was considered in light of her reduced EF and recent delivery but could not explain the entirety of her findings. Based on the collective clinical features and laboratory and imaging findings, the patient’s presentation was highly suggestive of EGPA with cardiac involvement. In addition to the elevated ventricular filling pressures on catheterization, she was hypotensive and hypoxic, leading to concern for cardiogenic shock. Dobutamine infusion and CYC were added to high-dose IV glucocorticoids as part of her treatment regimen. Eventually, the patient was weaned off dobutamine and she was treated with guideline-recommended heart failure medical therapy. Her eosinophil count normalized and her clinical status improved, allowing her to be discharged. Three days after discharge, she was found unresponsive with an initial rhythm of ventricular fibrillation from which she was resuscitated successfully. She experienced no neurologic sequelae, and an implantable cardiac device was placed for secondary prevention. She was treated with 5 months of daily CYC, after which time she was started on azathioprine while prednisone was slowly tapered. Her heart failure medical regimen continued to be optimized. Over time, the patient’s cardiac function improved, with serial echocardiograms showing recovery to an EF of 54%.
Clinical Pearls 1. EGPA has no diagnostic criteria; ANCA is positive in only 40% of patients with EGPA and cannot be used to establish or rule out the diagnosis. Rather, diagnosis is based on the constellation of symptoms/signs exhibited by the patient. 2. Cardiac involvement is an important cause of morbidity and mortality in EGPA. It can have a widerange of manifestations because EGPA can affect any level of cardiac structure.
e64 Pulmonary, Critical Care, and Sleep Pearls
3. Because of the rarity of EGPA, the impact of pregnancy on EGPA disease activity has not been established. 4. Patients with EGPA who become pregnant should be followed closely by a high-risk obstetrician and the physician managing their EGPA. Monitoring for disease activity should continue even after delivery. 5. Glucocorticoids are the basis of EGPA treatment, with other immunomodulating agents being used as adjunct therapy in severe cases.
Acknowledgments Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). 1999;78(1):26-37. Sablé-Fourtassou R, Cohen P, Mahr A, et al; French Vasculitis Study Group. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. 2005;143(9):632-638. Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007;298(6):655-669. Cohen P, Pagnoux C, Mahr A, et al; French Vasculitis Study Group. Churg-Strauss syndrome with poor-prognosis factors: a prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum. 2007;57(4):686-693. Pagnoux C, Guilpain P, Guillevin L. Churg-Strauss syndrome. Curr Opin Rheumatol. 2007;19(1):25-32. Ribi C, Cohen P, Pagnoux C, et al; French Vasculitis Study Group. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventytwo patients. Arthritis Rheum. 2008;58(2):586-594. Corradi D, Maestri R, Facchetti F. Postpartum Churg-Strauss syndrome with severe cardiac involvement: description of a case and review of the literature. Clin Rheumatol. 2009;28(6):739-743. Vinit J, Bielefeld P, Muller G, et al. Heart involvement in Churg-Strauss syndrome: retrospective study in French Burgundy population in past 10 years. Eur J Intern Med. 2010;21(4):341-346. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis. 2013;72(6):1011-1017.
[
149#2 CHEST FEBRUARY 2016
]
Pulmonary, Critical Care, and Sleep Pearls
]
A 39-Year-Old Postpartum Woman With Foot Drop and Shortness of Breath Atul K. Mehta, MD; Carol A. Langford, MD, MHS; David O. Taylor, MD; Michael Bolen, MD; and Anita J. Reddy, MD
A 39-year-old white woman with a history of adult-onset asthma, chronic sinusitis, and nasal polyposis presented to the ED with dyspnea and left lower extremity weakness and pain. Three months prior to her presentation she had an uncomplicated delivery of her second child, but during her pregnancy she experienced increasing asthma symptoms and nasal congestion. These symptoms progressed after delivery despite treatment with albuterol inhalers and antibiotics.
Physical Examination Findings Vitals signs on presentation were as follows: BP, 105/73 mm Hg; heart rate, 120 beats/min; respiratory rate, 18 breaths/min; oxygen saturation, 94% on room air (but she soon required supplemental oxygen); and temperature, 37.1 C. Pulmonary examination revealed bilateral rales. Cardiac examination revealed jugular venous distension, sinus tachycardia, and no S3 or S4. Musculoskeletal examination was normal. Neurologic examination showed intact cranial nerves, intact strength except for inability to dorsiflex or plantarflex the left foot, left lower extremity hyperalgesia, and decreased sensation of the lateral and dorsal aspects of the left foot.
Diagnostic Studies Pertinent laboratory data included the following (peak values): WBC count, 13.3 k/mL with 53% eosinophils; C-reactive protein, 19.9 mg/dL; erythrocyte sedimentation rate, 45 mm/h; creatine kinase,
AFFILIATIONS: From the Department of Internal Medicine (Dr Mehta), the Center for Vasculitis Care and Research (Dr Langford), Department of Rheumatic and Immunologic Diseases, the Department of Cardiovascular Medicine (Dr Taylor), the Imaging Institute (Dr Bolen), Cardiovascular Section, and the Respiratory Institute (Dr Reddy), Cleveland Clinic Foundation, Cleveland, OH.
journal.publications.chestnet.org
CHEST 2016; 149(2):e61–e64
1,240 U/L; myocardial band fraction, 65 ng/mL; troponin T, 4.35 ng/mL; N-terminal-pro brain natriuretic peptide, 6,883 pg/mL; and serum creatinine, 0.71. Urinalysis was normal. Chest CT scan displayed bilateral lung consolidations with pleural and pericardial effusions. MRI of the brain revealed frontal and parietal lobe punctate foci. ECG showed possible acute anterolateral infarct. Echocardiography demonstrated an ejection fraction (EF) of 25% with nearly the entire left ventricle exhibiting hypokinesis. The right ventricle had preserved function. Cardiac angiography revealed normal epicardial coronary arteries, but rightsided heart catheterization revealed elevated filling pressures. Cardiac MRI showed areas of myocarditis vs myocardial fibrosis (Fig 1). Additional laboratory results included negative antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCAs).
CORRESPONDENCE TO: Atul K. Mehta, MD, Internal Medicine Residency Program, Cleveland Clinic, 9500 Euclid Ave, NA10, Cleveland, OH 44114; e-mail: [email protected] Copyright Ó 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2015.10.051
e61
Figure 1 – Images from cardiac MRI with contrast. A, Mid- and basal-lung consolidations (*). B, Abnormal low signal along the left border of the interventricular septum (top arrow), bilateral pleural effusions (X), and a small pericardial effusion (lower arrow). C and D, Again, an abnormal low signal along the left border of the interventricular septum (black arrows) and an abnormal bright signal along the right side of the interventricular septum (white arrows). The overall imaging findings suggest endomyocarditis with mild adjacent laminar thrombus. (Reprinted with permission from Michael Bolen, MD.)
What is the diagnosis?
e62 Pulmonary, Critical Care, and Sleep Pearls
[
149#2 CHEST FEBRUARY 2016
]
Diagnosis: Eosinophilic granulomatosis with polyangiitis, with cardiac and neurologic involvement Discussion Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss) is an uncommon, potentially fatal, primary systemic vasculitis. It often affects patients between the ages of 40 and 60 years old, with an annual incidence of 2.4 people per million. EGPA is defined by eosinophil-rich and necrotizing granulomatous inflammation (often involving the respiratory tract) and necrotizing vasculitis predominantly affecting small to medium vessels. The clinical features are thought of as having three phases: an allergic phase (asthma, nasal polyps, rhinosinusitis), an eosinophilic phase (peripheral and tissue eosinophilia), and a vasculitic phase (nerve, skin, lung, kidney, GI tract, and heart). Although these phases may not be sequential, the median time from asthma symptoms to necrotizing vasculitis is 3 to 4 years. To date, there are no established diagnostic criteria for EGPA; the diagnosis is based on the constellation of clinical findings and the exclusion of other possible causes. Although an association between EGPA and antimyeloperoxidase-/peri-nuclear ANCA exists, only about 40% of patients with EGPA are ANCA positive. Some studies have found ANCA-positive EGPA to be associated with glomerulonephritis, whereas patients who are ANCA negative more commonly have cardiac involvement. EGPA has a wide range of cardiac manifestations and can affect multiple cardiac structures (Table 1). ECG changes can be nonspecific. Echocardiography should be performed on all patients presenting with EGPA and TABLE 1
] Possible Cardiac Manifestations of EGPA
Manifestation
can show pericardial effusion or ventricular dysfunction. If heart involvement is suspected, cardiac MRI can provide detailed imaging of the pericardium and the myocardium supporting the presence of inflammation and/or fibrosis. Cardiac involvement has been reported in 15% to 52% of patients with EGPA and is responsible for approximately 39% of mortality, making it an important manifestation in this population. Treatment of EGPA is based on disease severity. Systemic glucocorticoids represent the foundation of treatment regimens and may be the only required therapy for patients with nonsevere disease. For patients with organ- or life-threatening features, specifically cardiac disease, combined treatment with glucocorticoids and cyclophosphamide (CYC) has improved patient outcomes. With this approach, glucocorticoids are tapered slowly, and CYC is replaced after 3 to 6 months by less toxic medications (azathioprine, methotrexate) for maintenance therapy. It is unknown whether pregnancy impacts EGPA disease activity, including initial diagnosis or relapse. Because of its rarity, there are few reported cases describing pregnancy and the postpartum period in women with quiescent or active EGPA. In the available reports of those who had active EGPA, all treatment regimens included glucocorticoids, with disease severity and pregnancy trimester influencing the use of other immunosuppressive agents. CYC, methotrexate, and mycophenolate mofetil are all contraindicated during pregnancy, although azathioprine has been used during pregnancy after careful assessment of the relative risks and benefits. Prognosis of both mother and fetus depend on the degree of organ involvement, with cardiac involvement having the worst outcomes. Women with EGPA who become pregnant should be followed by a high-risk obstetrician and the physician managing their EGPA. Close monitoring should continue during the immediate postpartum period for emergence of disease activity.
Pericarditis
Clinical Course
Myocarditis
The patient had clinical features consistent with EGPA, including worsening of adult-onset asthma symptoms, sinus disease with polyposis, peripheral eosinophilia, motor and sensory mononeuritis multiplex, pulmonary infiltrates, possible CNS involvement by brain imaging, and nonischemic cardiomyopathy. Hypereosinophilic syndrome was considered another diagnostic possibility for the case because it can present similarly to EGPA with multiorgan eosinophilic injury but it is not
Acute coronary syndrome Arrhythmias (ie, atrioventricular block, ventricular arrhythmias) Congestive heart failure Valvular heart disease (mitral valve regurgitation, aortic valve regurgitation) Sudden death EGPA ¼ eosinophilic granulomatosis with polyangiitis.
journal.publications.chestnet.org
e63
associated with vasculitis. Postpartum cardiomyopathy was considered in light of her reduced EF and recent delivery but could not explain the entirety of her findings. Based on the collective clinical features and laboratory and imaging findings, the patient’s presentation was highly suggestive of EGPA with cardiac involvement. In addition to the elevated ventricular filling pressures on catheterization, she was hypotensive and hypoxic, leading to concern for cardiogenic shock. Dobutamine infusion and CYC were added to high-dose IV glucocorticoids as part of her treatment regimen. Eventually, the patient was weaned off dobutamine and she was treated with guideline-recommended heart failure medical therapy. Her eosinophil count normalized and her clinical status improved, allowing her to be discharged. Three days after discharge, she was found unresponsive with an initial rhythm of ventricular fibrillation from which she was resuscitated successfully. She experienced no neurologic sequelae, and an implantable cardiac device was placed for secondary prevention. She was treated with 5 months of daily CYC, after which time she was started on azathioprine while prednisone was slowly tapered. Her heart failure medical regimen continued to be optimized. Over time, the patient’s cardiac function improved, with serial echocardiograms showing recovery to an EF of 54%.
Clinical Pearls 1. EGPA has no diagnostic criteria; ANCA is positive in only 40% of patients with EGPA and cannot be used to establish or rule out the diagnosis. Rather, diagnosis is based on the constellation of symptoms/signs exhibited by the patient. 2. Cardiac involvement is an important cause of morbidity and mortality in EGPA. It can have a widerange of manifestations because EGPA can affect any level of cardiac structure.
e64 Pulmonary, Critical Care, and Sleep Pearls
3. Because of the rarity of EGPA, the impact of pregnancy on EGPA disease activity has not been established. 4. Patients with EGPA who become pregnant should be followed closely by a high-risk obstetrician and the physician managing their EGPA. Monitoring for disease activity should continue even after delivery. 5. Glucocorticoids are the basis of EGPA treatment, with other immunomodulating agents being used as adjunct therapy in severe cases.
Acknowledgments Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). 1999;78(1):26-37. Sablé-Fourtassou R, Cohen P, Mahr A, et al; French Vasculitis Study Group. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. 2005;143(9):632-638. Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007;298(6):655-669. Cohen P, Pagnoux C, Mahr A, et al; French Vasculitis Study Group. Churg-Strauss syndrome with poor-prognosis factors: a prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum. 2007;57(4):686-693. Pagnoux C, Guilpain P, Guillevin L. Churg-Strauss syndrome. Curr Opin Rheumatol. 2007;19(1):25-32. Ribi C, Cohen P, Pagnoux C, et al; French Vasculitis Study Group. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventytwo patients. Arthritis Rheum. 2008;58(2):586-594. Corradi D, Maestri R, Facchetti F. Postpartum Churg-Strauss syndrome with severe cardiac involvement: description of a case and review of the literature. Clin Rheumatol. 2009;28(6):739-743. Vinit J, Bielefeld P, Muller G, et al. Heart involvement in Churg-Strauss syndrome: retrospective study in French Burgundy population in past 10 years. Eur J Intern Med. 2010;21(4):341-346. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis. 2013;72(6):1011-1017.
[
149#2 CHEST FEBRUARY 2016
]