Difficult Cases Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Vasculitis) Eugene Choo, MDa,b, and Dennis Ledford, MDc,d,e INFORMATION FOR CATEGORY 1 CME CREDIT
Activity Objectives
Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.
1. To identify the clinical features of eosinophilic granulomatosis with polyangiitis (EGPA).
Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The accompanying tests may only be submitted online at www.jaciinpractice.org/. Fax or other copies will not be accepted.
2. To review the diagnostic evaluation of EGPA.
Date of Original Release: May 1, 2015. Credit may be obtained for these courses until June 30, 2016.
Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: E. Choo received travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI) for the 2015 AAAAI Annual Meeting; is on Meda Pharmaceuticals Speaker Advisory Board; and has stock in North Houston MedPharm LLC. D. Ledford has received travel support from the AAAAI as a member of the Joint Council of Allergy Asthma and Immunology; has received consultancy fees from Genentech and GlaxoSmithKline; is employed by the Veterans Administration, University of South Florida Morsani College of Medicine, and the Academic Allergy Asthma and Immunology Associates of Tampa Bay; has provided expert testimony from Shook Hardy Bacon, Saieva and Stine, Richard Benjamin Wilks, Fowler White Burnett, and Burr Murman & Tonelli; has received research support from Chugai Data Safety, as a board member, Forest Pharmaceuticals, Merck, Circassia, Teva, and Genentech; has received lecture fees from Meda Pharmaceuticals, Genentech, Novartis, Merck, AstraZeneca, and Teva; has received payment for manuscript preparation from Genentech; has a patent through the University of South Florida; receives royalties from UpToDate, Springer, and Informa; and has received payment for developing educational presentations from Novartis and Current Views in Allergy Asthma and Immunology, Regents University.
Copyright Statement: Copyright Ó 2015-2017. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum of 1 AMA PRA Category 1 Credit. Physicians should only claim credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Eugene Choo, MD, and Dennis Ledford, MD
3. To obtain an overview of the treatment of EGPA. Recognition of Commercial Support: This CME has not received external commercial support.
The Difficult Cases Feature is based on the Difficult Cases Course presented at the AAAAI Annual Meeting and coordinated by the AAAAI New Allergist-Immunologist Assembly (NAIA). View the entire presentation and obtain CME by visiting the JACI: In Practice homepage www.jaci-inpractice.org. Key words: Asthma; Eosinophilic granulomatosis with polyangiitis; Churg-Strauss vasculitis; Pulmonary opacities
a
Allergy & Asthma Associates, Houston, Tex Past-Assistant Professor of Medicine, Division of Allergy/Immunology, National Jewish Health, Denver, Colo c Allergy, Asthma & Immunology Associates of Tampa Bay, Tampa, Fla d Ellsworth and Mabel Simmons Professor of Allergy/Immunology, Tampa, Fla e Past-President of Medical Faculty, University of South Florida College of Medicine, Tampa, Fla Conflict of interest: E. Choo received travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI) for the 2015 AAAAI Annual Meeting; is on Meda Pharmaceuticals Speaker Advisory Board; and has stock in North Houston MedPharm LLC. D. Ledford has received travel support from the AAAAI as a member of the Joint Council of Allergy Asthma and Immunology; has received consultancy fees from Genentech and GlaxoSmithKline; is employed by the Veterans Administration, University of South Florida Morsani College of Medicine, and the Academic Allergy Asthma and Immunology Associates of Tampa Bay; has provided expert testimony from Shook Hardy Bacon, Saieva and b
466
Stine, Richard Benjamin Wilks, Fowler White Burnett, and Burr Murman & Tonelli; has received research support from Chugai Data Safety, as a board member, Forest Pharmaceuticals, Merck, Circassia, Teva, and Genentech; has received lecture fees from Meda Pharmaceuticals, Genentech, Novartis, Merck, AstraZeneca, and Teva; has received payment for manuscript preparation from Genentech; has a patent through the University of South Florida; receives royalties from UpToDate, Springer, and Informa; and has received payment for developing educational presentations from Novartis and Current Views in Allergy Asthma and Immunology, Regents University. Received for publication February 23, 2015; revised February 23, 2015; accepted for publication February 25, 2015. Corresponding author: Eugene Choo, MD, FAAAAI, FACAAI, 13114 FM 1960 Road West Suite 100, Houston, TX 77065. E-mail: [email protected]. 2213-2198 Ó 2015 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2015.02.010
J ALLERGY CLIN IMMUNOL PRACT VOLUME 3, NUMBER 3
The patient is a 47-year-old woman with chronic sinusitis, allergic rhinitis, atopic dermatitis, and gastroesophageal reflux disease who was referred for worsening respiratory symptoms and a new pulmonary lesion. She had a history of asthma since age 19 years and quit smoking after 23 pack-years. In recent years, worsening respiratory symptoms necessitated increased asthma medications. Over the past year, she also began to note systemic symptoms, including fatigue, fever, chills, night sweats, abdominal pain, intermittent nonpruritic rash on thighs and buttocks, mild bilateral thigh pain, and bilateral hand numbness. Previous laboratory evaluation was significant for leukocytosis (14,000 cells/uL), eosinophilia (peaking at 15.4%), and elevated IgE level (7375 kU/L). The allergic bronchopulmonary aspergillosis panel was negative for Aspergillus fumigatusespecific precipitins and specific IgE. Results for antineutrophil cytoplasmic antibodies and purified protein derivative skin testing were negative. Computed tomography (CT) of the chest 5 months before presentation revealed a 3-mm right middle-lobe pulmonary nodule and a 4 3.1 cm left lower-lobe mass-like pulmonary lesion. Transbronchial biopsy showed an inflamed granulomatous lesion with occasional multinucleated giant cells. It was negative for malignancy, acid-fast bacillus, fungus, or pneumocystis. Symptoms dramatically improved after systemic corticosteroid therapy (starting with 40 mg of prednisone per day and tapering over 2 months), and her left lower-lobe pulmonary mass decreased in size to 2.3 2.1 cm. On presentation 5 months later, physical examination was significant only for minimal eczematoid areas on bilateral forearms and mildly inflamed nasal mucosa without ulcerations. Neurologic examination was unremarkable, and she was not hypertensive. Pulmonary function testing demonstrated hyperinflation, airflow limitation, and 10% bronchodilator reversibility. CT of the chest now showed a focal dense linear left lower-lobe lesion (no longer suggestive of a mass), peripheral bronchiectasis (not central), and bilateral multifocal ground glass
CHOO AND LEDFORD
467
areas suggestive of infection/inflammation. CT of the sinus revealed mild to moderate chronic ethmoid sinusitis. Repeat transbronchial biopsy revealed moderate eosinophilic inflammation and thickened subbasal lamina in the bronchial wall, centrally necrotizing granulomas, air space eosinophils and neutrophils, and airway fibrin deposition. The differential diagnosis for patients with persistent respiratory symptoms and migratory/transient pulmonary opacities is extensive, including infections (fungal and parasitic etiologies must be kept in mind especially if there is a supportive travel history), allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, drug reaction (eg, methotrexate or cyclophosphamide), hematopoietic malignancies (eg, Langerhans cell histiocytosis), and vasculitis or autoimmune diseases (eg, eosinophilic granulomatosis with polyangiitis [EGPA] or ChurgStrauss vasculitis), granulomatosis with polyangiitis (Wegener vasculitis), microscopic polyangiitis, or antiglomerular basement membrane antibody disease. In summary, this patient met at least 4 of 6 American College of Rheumatology criteria for the diagnosis of EGPA: asthma, eosinophilia (>10% blood white cells), migratory/transient pulmonary opacities, and paranasal sinus abnormality. She also had a history suggestive of neuropathy. The presence of 4 or more American College of Rheumatology criteria is associated with 85% sensitivity and 99.7% specificity for EGPA; however, these criteria are not intended for routine clinical application but for identifying patients for clinical trials. Because there are many ways EGPA could present to the office, it is important to keep in mind. Examples of potential clinical presentations include asthmatic patients with foot drop, peripheral blood eosinophilia and pulmonary infiltrates, eosinophilic upper airway disease (ear or sinus), eosinophilic pleural or pericardial effusion, or palpable purpura. Further information can be obtained by viewing the original Difficult Cases presentation in this article’s Online Repository at www.jaci-inpractice.org.
Activity Objectives
Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.
1. To identify the clinical features of eosinophilic granulomatosis with polyangiitis (EGPA).
Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The accompanying tests may only be submitted online at www.jaciinpractice.org/. Fax or other copies will not be accepted.
2. To review the diagnostic evaluation of EGPA.
Date of Original Release: May 1, 2015. Credit may be obtained for these courses until June 30, 2016.
Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: E. Choo received travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI) for the 2015 AAAAI Annual Meeting; is on Meda Pharmaceuticals Speaker Advisory Board; and has stock in North Houston MedPharm LLC. D. Ledford has received travel support from the AAAAI as a member of the Joint Council of Allergy Asthma and Immunology; has received consultancy fees from Genentech and GlaxoSmithKline; is employed by the Veterans Administration, University of South Florida Morsani College of Medicine, and the Academic Allergy Asthma and Immunology Associates of Tampa Bay; has provided expert testimony from Shook Hardy Bacon, Saieva and Stine, Richard Benjamin Wilks, Fowler White Burnett, and Burr Murman & Tonelli; has received research support from Chugai Data Safety, as a board member, Forest Pharmaceuticals, Merck, Circassia, Teva, and Genentech; has received lecture fees from Meda Pharmaceuticals, Genentech, Novartis, Merck, AstraZeneca, and Teva; has received payment for manuscript preparation from Genentech; has a patent through the University of South Florida; receives royalties from UpToDate, Springer, and Informa; and has received payment for developing educational presentations from Novartis and Current Views in Allergy Asthma and Immunology, Regents University.
Copyright Statement: Copyright Ó 2015-2017. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum of 1 AMA PRA Category 1 Credit. Physicians should only claim credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Eugene Choo, MD, and Dennis Ledford, MD
3. To obtain an overview of the treatment of EGPA. Recognition of Commercial Support: This CME has not received external commercial support.
The Difficult Cases Feature is based on the Difficult Cases Course presented at the AAAAI Annual Meeting and coordinated by the AAAAI New Allergist-Immunologist Assembly (NAIA). View the entire presentation and obtain CME by visiting the JACI: In Practice homepage www.jaci-inpractice.org. Key words: Asthma; Eosinophilic granulomatosis with polyangiitis; Churg-Strauss vasculitis; Pulmonary opacities
a
Allergy & Asthma Associates, Houston, Tex Past-Assistant Professor of Medicine, Division of Allergy/Immunology, National Jewish Health, Denver, Colo c Allergy, Asthma & Immunology Associates of Tampa Bay, Tampa, Fla d Ellsworth and Mabel Simmons Professor of Allergy/Immunology, Tampa, Fla e Past-President of Medical Faculty, University of South Florida College of Medicine, Tampa, Fla Conflict of interest: E. Choo received travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI) for the 2015 AAAAI Annual Meeting; is on Meda Pharmaceuticals Speaker Advisory Board; and has stock in North Houston MedPharm LLC. D. Ledford has received travel support from the AAAAI as a member of the Joint Council of Allergy Asthma and Immunology; has received consultancy fees from Genentech and GlaxoSmithKline; is employed by the Veterans Administration, University of South Florida Morsani College of Medicine, and the Academic Allergy Asthma and Immunology Associates of Tampa Bay; has provided expert testimony from Shook Hardy Bacon, Saieva and b
466
Stine, Richard Benjamin Wilks, Fowler White Burnett, and Burr Murman & Tonelli; has received research support from Chugai Data Safety, as a board member, Forest Pharmaceuticals, Merck, Circassia, Teva, and Genentech; has received lecture fees from Meda Pharmaceuticals, Genentech, Novartis, Merck, AstraZeneca, and Teva; has received payment for manuscript preparation from Genentech; has a patent through the University of South Florida; receives royalties from UpToDate, Springer, and Informa; and has received payment for developing educational presentations from Novartis and Current Views in Allergy Asthma and Immunology, Regents University. Received for publication February 23, 2015; revised February 23, 2015; accepted for publication February 25, 2015. Corresponding author: Eugene Choo, MD, FAAAAI, FACAAI, 13114 FM 1960 Road West Suite 100, Houston, TX 77065. E-mail: [email protected]. 2213-2198 Ó 2015 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2015.02.010
J ALLERGY CLIN IMMUNOL PRACT VOLUME 3, NUMBER 3
The patient is a 47-year-old woman with chronic sinusitis, allergic rhinitis, atopic dermatitis, and gastroesophageal reflux disease who was referred for worsening respiratory symptoms and a new pulmonary lesion. She had a history of asthma since age 19 years and quit smoking after 23 pack-years. In recent years, worsening respiratory symptoms necessitated increased asthma medications. Over the past year, she also began to note systemic symptoms, including fatigue, fever, chills, night sweats, abdominal pain, intermittent nonpruritic rash on thighs and buttocks, mild bilateral thigh pain, and bilateral hand numbness. Previous laboratory evaluation was significant for leukocytosis (14,000 cells/uL), eosinophilia (peaking at 15.4%), and elevated IgE level (7375 kU/L). The allergic bronchopulmonary aspergillosis panel was negative for Aspergillus fumigatusespecific precipitins and specific IgE. Results for antineutrophil cytoplasmic antibodies and purified protein derivative skin testing were negative. Computed tomography (CT) of the chest 5 months before presentation revealed a 3-mm right middle-lobe pulmonary nodule and a 4 3.1 cm left lower-lobe mass-like pulmonary lesion. Transbronchial biopsy showed an inflamed granulomatous lesion with occasional multinucleated giant cells. It was negative for malignancy, acid-fast bacillus, fungus, or pneumocystis. Symptoms dramatically improved after systemic corticosteroid therapy (starting with 40 mg of prednisone per day and tapering over 2 months), and her left lower-lobe pulmonary mass decreased in size to 2.3 2.1 cm. On presentation 5 months later, physical examination was significant only for minimal eczematoid areas on bilateral forearms and mildly inflamed nasal mucosa without ulcerations. Neurologic examination was unremarkable, and she was not hypertensive. Pulmonary function testing demonstrated hyperinflation, airflow limitation, and 10% bronchodilator reversibility. CT of the chest now showed a focal dense linear left lower-lobe lesion (no longer suggestive of a mass), peripheral bronchiectasis (not central), and bilateral multifocal ground glass
CHOO AND LEDFORD
467
areas suggestive of infection/inflammation. CT of the sinus revealed mild to moderate chronic ethmoid sinusitis. Repeat transbronchial biopsy revealed moderate eosinophilic inflammation and thickened subbasal lamina in the bronchial wall, centrally necrotizing granulomas, air space eosinophils and neutrophils, and airway fibrin deposition. The differential diagnosis for patients with persistent respiratory symptoms and migratory/transient pulmonary opacities is extensive, including infections (fungal and parasitic etiologies must be kept in mind especially if there is a supportive travel history), allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, drug reaction (eg, methotrexate or cyclophosphamide), hematopoietic malignancies (eg, Langerhans cell histiocytosis), and vasculitis or autoimmune diseases (eg, eosinophilic granulomatosis with polyangiitis [EGPA] or ChurgStrauss vasculitis), granulomatosis with polyangiitis (Wegener vasculitis), microscopic polyangiitis, or antiglomerular basement membrane antibody disease. In summary, this patient met at least 4 of 6 American College of Rheumatology criteria for the diagnosis of EGPA: asthma, eosinophilia (>10% blood white cells), migratory/transient pulmonary opacities, and paranasal sinus abnormality. She also had a history suggestive of neuropathy. The presence of 4 or more American College of Rheumatology criteria is associated with 85% sensitivity and 99.7% specificity for EGPA; however, these criteria are not intended for routine clinical application but for identifying patients for clinical trials. Because there are many ways EGPA could present to the office, it is important to keep in mind. Examples of potential clinical presentations include asthmatic patients with foot drop, peripheral blood eosinophilia and pulmonary infiltrates, eosinophilic upper airway disease (ear or sinus), eosinophilic pleural or pericardial effusion, or palpable purpura. Further information can be obtained by viewing the original Difficult Cases presentation in this article’s Online Repository at www.jaci-inpractice.org.
