Accepted Manuscript Atypical vasculitis mimicking chronic thromboembolic pulmonary hypertension Jérémie Dion, MD, Benjamin Terrier, MD, PhD, Xavier Jaïs, MD, Anas Mehdaoui, MD, Caroline Sattler, MD, David Amar, MD, Pascal Cohen, MD, Loïc Guillevin, MD, Luc Mouthon, MD, PhD PII:
S0002-9343(15)00512-4
DOI:
10.1016/j.amjmed.2015.05.028
Reference:
AJM 13026
To appear in:
The American Journal of Medicine
Received Date: 30 April 2015 Revised Date:
14 May 2015
Accepted Date: 14 May 2015
Please cite this article as: Dion J, Terrier B, Jaïs X, Mehdaoui A, Sattler C, Amar D, Cohen P, Guillevin L, Mouthon L, on behalf of the French Vasculitis Study Group (FVSG), Atypical vasculitis mimicking chronic thromboembolic pulmonary hypertension, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.05.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Atypical vasculitis mimicking chronic thromboembolic pulmonary hypertension. Jérémie Dion1, MD Benjamin Terrier1, MD, PhD, Xavier Jaïs2, MD, Anas Mehdaoui3, MD, Caroline Sattler2, MD, David Amar2, MD Pascal Cohen1, MD, Loïc Guillevin1, MD, and Luc Mouthon1, MD, PhD, on behalf of the French Vasculitis Study Group (FVSG) Department of Internal Medicine, National Referral Center for Rare Autoimmune and
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1
Systemic Diseases, Cochin Hospital, Assistance Publique–Hôpitaux de Paris (AP–HP), Université Paris Descartes, Paris; 2 Department of Pulmonology, National Referral Center for
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Pulmonary Hypertension, Bicêtre Hospital, AP–HP, Université Paris Sud, Le Kremlin Bicêtre, France.3 Departement of Pulmonology, Evreux Hospital, Centre Hospitalier Eure et
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Seine.
Address correspondence to Dr Benjamin Terrier, Department of Internal Medicine, Cochin Hospital, 27, rue du Faubourg Saint-Jacques, 75679 Paris Cedex 14, France. Phone: +33 (0)1 58 41 20 31; Fax: +33 (0)1 58 41 14 50; E-mail: [email protected].
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Funding sources and potential conflict of interest related to this publication: Dr Jérémie Dion: Funding: none, conflict of interest: none Dr Benjamin Terrier: Funding: none, conflict of interest: none
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Dr Anas Mehdaoui: Funding: none, conflict of interest: none
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Dr Xavier Jaïs: Funding: none, conflict of interest: none Dr Caroline Sattler: none Dr David Amar: Funding: none, conflict of interest: none Dr Pascal Cohen: Funding: none, conflict of interest: none Pr Loïc Guillevin: Funding: none, conflict of interest: none Pr Luc Mouthon: Funding: none, conflict of interest: none All authors had access to the data and a role in writing the manuscript. Text body: 660 words
ACCEPTED MANUSCRIPT To the editor A 26-year-old man was referred for evaluation of chronic cough, dyspnea (NYHA class II) and paresthesias. He had a history of allergic rhinitis but no asthma. Physical examination was unremarkable. An extensive work-up revealed mild eosinophilia at 1 600/mm3, ground glass
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opacities, subpleural opacities and mild pleural effusion on chest CT-scan, distal axonal neuropathy on electromyography and mixed abnormalities on pulmonary function test with forced expiratory volume 66%, total lung capacity 70% and diffusing capacity for carbon
SC
monoxide 65% (percentages of predicted value). Bronchoalveolar lavage showed alveolitis with 900 000 cells/mm3 (83% macrophages, 12% Lymphocytes, 5% neutrophils, no
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eosinophils). Test for anti-neutrophil cytoplasm antibody (ANCA) was negative. Surgical lung biopsy revealed necrotizing granulomatous vasculitis, without giant cells, involving small-sized arteries and veinules. According to the revised 2012 Chapel Hill consensus conference, the patient was classified in ANCA-associated vasculitis despite negativity for
eosinophilic
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ANCA, without possibility to distinguish between granulomatosis with polyangiitis and granulomatosis
with
polyangiitis.
Treatment
consisted
in
pulses
of
methylprednisolone followed by prednisone at 1 mg/kg/day, secondarily associated with
EP
rituximab (375mg/m²/week) because of corticodependance, leading to improvement of dyspnea and CT-scan abnormalities.
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Three months later, the patient noticed a worsening of dyspnea (NYHA III). Six-minute walking distance was 555 m with desaturation at 78%. An echocardiography was performed and revealed pulmonary hypertension with estimated right ventricular systolic pressure at 55 mmHg. Ventilation-perfusion (VQ) scan showed multiple perfusion defects suggestive of thromboembolic disease (Figure 1A). The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) was therefore suspected. A right-heart catheterization was performed and confirmed the presence of precapillary pulmonary hypertension with mean pulmonary
ACCEPTED MANUSCRIPT artery pressure (mPAP) at 41 mmHg and pulmonary capillary wedge pressure at 3 mmHg. Computed tomography pulmonary angiogram (CTPA) did not show any signs of thrombosis. Pulmonary angiography ruled out chronic thromboembolic disease but revealed a “dead-tree” picture with very narrow peripheral pulmonary vascular structures (Figure 1B). Diagnosis of arteries
vasculitis
was
finally
made.
Treatment
with
intravenous
RI PT
pulmonary
cyclophosphamide (600 mg/m2) was initiated in association with increased corticosteroids and vitamin K antagonists. The assessment after six pulses of cyclophosphamide revealed a
SC
marked improvement, in functional score (NYHA II) and exercise capacity (6-minute walking distance at 594 m). Right hearth catheterization showed a decrease in mPAP from 41 to 34
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mmHg with unchanged cardiac index. In contrast, VQ scan remained unchanged. Here, we report ANCA associated vasculitis-related pulmonary arteries involvement highly suggestive of CTEPH on VQ scan. A greater risk of pulmonary embolism was previously demonstrated in ANCA associated vasculitis1, that could lead to misdiagnosis of CTEPH in
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this situation. CTEPH is a rare complication of pulmonary embolism characterized by the presence of multiple perfusion defects on VQ scan, evidence of organized emboli on CTPA and pulmonary angiography and on right hearth catheterization. Pulmonary vasculitis was
EP
described in large vessels vasculitis, but was very rarely reported in ANCA associated vasculitis. Four cases of ANCA associated vasculitis-related PH were reported but none of
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them had CTEPH features2 and in another case of granulomatosis with polyangiitis, PH was related to proximal pulmonary involvement but no data on evolution was available3. Despite a treatment by rituximab, validated in all ANCA associated vasculitis except eosinophilic granulomatosis with polyangiitis, the patient worsened and developed pulmonary vasculitis. Interestingly, cyclophosphamide therapy led to a marked improvement, confirming the vasculitic-related process. This case illustrates that pulmonary vasculitis can mimic
ACCEPTED MANUSCRIPT CTEPH and should be investigated in patients with PH and ANCA associated vasculitis, allowing appropriate therapeutic management.
References Allenbach Y, Seror R, Pagnoux C, et al. High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: a systematic retrospective study on 1130 patients. Ann Rheum Dis. 2009;68(4):564-567. doi:10.1136/ard.2008.099051.
2.
Launay D, Souza R, Guillevin L, et al. Pulmonary arterial hypertension in ANCAassociated vasculitis. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG World Assoc Sarcoidosis Granulomatous Disord. 2006;23(3):223-228.
3.
Doyle DJ, Fanning NF, Silke CS, et al. Wegener’s Granulomatosis of the Main Pulmonary Arteries: Imaging Findings. Clin Radiol. 2003;58(4):329-331. doi:10.1016/S0009-9260(02)00517-2.
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1.
ACCEPTED MANUSCRIPT
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Figure 1. Ventilation-perfusion (VQ) scan and pulmonary angiography findings. (A) Baseline VQ scan revealed multiple perfusion defects consistent with thromboembolic disease. (B) Pulmonary angiography (right and left anterior views) ruled out chronic thromboembolic disease but demonstrated poor peripheral perfusion with a typical “dead tree” aspect.
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ACCEPTED MANUSCRIPT
S0002-9343(15)00512-4
DOI:
10.1016/j.amjmed.2015.05.028
Reference:
AJM 13026
To appear in:
The American Journal of Medicine
Received Date: 30 April 2015 Revised Date:
14 May 2015
Accepted Date: 14 May 2015
Please cite this article as: Dion J, Terrier B, Jaïs X, Mehdaoui A, Sattler C, Amar D, Cohen P, Guillevin L, Mouthon L, on behalf of the French Vasculitis Study Group (FVSG), Atypical vasculitis mimicking chronic thromboembolic pulmonary hypertension, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.05.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Atypical vasculitis mimicking chronic thromboembolic pulmonary hypertension. Jérémie Dion1, MD Benjamin Terrier1, MD, PhD, Xavier Jaïs2, MD, Anas Mehdaoui3, MD, Caroline Sattler2, MD, David Amar2, MD Pascal Cohen1, MD, Loïc Guillevin1, MD, and Luc Mouthon1, MD, PhD, on behalf of the French Vasculitis Study Group (FVSG) Department of Internal Medicine, National Referral Center for Rare Autoimmune and
RI PT
1
Systemic Diseases, Cochin Hospital, Assistance Publique–Hôpitaux de Paris (AP–HP), Université Paris Descartes, Paris; 2 Department of Pulmonology, National Referral Center for
SC
Pulmonary Hypertension, Bicêtre Hospital, AP–HP, Université Paris Sud, Le Kremlin Bicêtre, France.3 Departement of Pulmonology, Evreux Hospital, Centre Hospitalier Eure et
M AN U
Seine.
Address correspondence to Dr Benjamin Terrier, Department of Internal Medicine, Cochin Hospital, 27, rue du Faubourg Saint-Jacques, 75679 Paris Cedex 14, France. Phone: +33 (0)1 58 41 20 31; Fax: +33 (0)1 58 41 14 50; E-mail: [email protected].
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Funding sources and potential conflict of interest related to this publication: Dr Jérémie Dion: Funding: none, conflict of interest: none Dr Benjamin Terrier: Funding: none, conflict of interest: none
EP
Dr Anas Mehdaoui: Funding: none, conflict of interest: none
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Dr Xavier Jaïs: Funding: none, conflict of interest: none Dr Caroline Sattler: none Dr David Amar: Funding: none, conflict of interest: none Dr Pascal Cohen: Funding: none, conflict of interest: none Pr Loïc Guillevin: Funding: none, conflict of interest: none Pr Luc Mouthon: Funding: none, conflict of interest: none All authors had access to the data and a role in writing the manuscript. Text body: 660 words
ACCEPTED MANUSCRIPT To the editor A 26-year-old man was referred for evaluation of chronic cough, dyspnea (NYHA class II) and paresthesias. He had a history of allergic rhinitis but no asthma. Physical examination was unremarkable. An extensive work-up revealed mild eosinophilia at 1 600/mm3, ground glass
RI PT
opacities, subpleural opacities and mild pleural effusion on chest CT-scan, distal axonal neuropathy on electromyography and mixed abnormalities on pulmonary function test with forced expiratory volume 66%, total lung capacity 70% and diffusing capacity for carbon
SC
monoxide 65% (percentages of predicted value). Bronchoalveolar lavage showed alveolitis with 900 000 cells/mm3 (83% macrophages, 12% Lymphocytes, 5% neutrophils, no
M AN U
eosinophils). Test for anti-neutrophil cytoplasm antibody (ANCA) was negative. Surgical lung biopsy revealed necrotizing granulomatous vasculitis, without giant cells, involving small-sized arteries and veinules. According to the revised 2012 Chapel Hill consensus conference, the patient was classified in ANCA-associated vasculitis despite negativity for
eosinophilic
TE D
ANCA, without possibility to distinguish between granulomatosis with polyangiitis and granulomatosis
with
polyangiitis.
Treatment
consisted
in
pulses
of
methylprednisolone followed by prednisone at 1 mg/kg/day, secondarily associated with
EP
rituximab (375mg/m²/week) because of corticodependance, leading to improvement of dyspnea and CT-scan abnormalities.
AC C
Three months later, the patient noticed a worsening of dyspnea (NYHA III). Six-minute walking distance was 555 m with desaturation at 78%. An echocardiography was performed and revealed pulmonary hypertension with estimated right ventricular systolic pressure at 55 mmHg. Ventilation-perfusion (VQ) scan showed multiple perfusion defects suggestive of thromboembolic disease (Figure 1A). The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) was therefore suspected. A right-heart catheterization was performed and confirmed the presence of precapillary pulmonary hypertension with mean pulmonary
ACCEPTED MANUSCRIPT artery pressure (mPAP) at 41 mmHg and pulmonary capillary wedge pressure at 3 mmHg. Computed tomography pulmonary angiogram (CTPA) did not show any signs of thrombosis. Pulmonary angiography ruled out chronic thromboembolic disease but revealed a “dead-tree” picture with very narrow peripheral pulmonary vascular structures (Figure 1B). Diagnosis of arteries
vasculitis
was
finally
made.
Treatment
with
intravenous
RI PT
pulmonary
cyclophosphamide (600 mg/m2) was initiated in association with increased corticosteroids and vitamin K antagonists. The assessment after six pulses of cyclophosphamide revealed a
SC
marked improvement, in functional score (NYHA II) and exercise capacity (6-minute walking distance at 594 m). Right hearth catheterization showed a decrease in mPAP from 41 to 34
M AN U
mmHg with unchanged cardiac index. In contrast, VQ scan remained unchanged. Here, we report ANCA associated vasculitis-related pulmonary arteries involvement highly suggestive of CTEPH on VQ scan. A greater risk of pulmonary embolism was previously demonstrated in ANCA associated vasculitis1, that could lead to misdiagnosis of CTEPH in
TE D
this situation. CTEPH is a rare complication of pulmonary embolism characterized by the presence of multiple perfusion defects on VQ scan, evidence of organized emboli on CTPA and pulmonary angiography and on right hearth catheterization. Pulmonary vasculitis was
EP
described in large vessels vasculitis, but was very rarely reported in ANCA associated vasculitis. Four cases of ANCA associated vasculitis-related PH were reported but none of
AC C
them had CTEPH features2 and in another case of granulomatosis with polyangiitis, PH was related to proximal pulmonary involvement but no data on evolution was available3. Despite a treatment by rituximab, validated in all ANCA associated vasculitis except eosinophilic granulomatosis with polyangiitis, the patient worsened and developed pulmonary vasculitis. Interestingly, cyclophosphamide therapy led to a marked improvement, confirming the vasculitic-related process. This case illustrates that pulmonary vasculitis can mimic
ACCEPTED MANUSCRIPT CTEPH and should be investigated in patients with PH and ANCA associated vasculitis, allowing appropriate therapeutic management.
References Allenbach Y, Seror R, Pagnoux C, et al. High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: a systematic retrospective study on 1130 patients. Ann Rheum Dis. 2009;68(4):564-567. doi:10.1136/ard.2008.099051.
2.
Launay D, Souza R, Guillevin L, et al. Pulmonary arterial hypertension in ANCAassociated vasculitis. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG World Assoc Sarcoidosis Granulomatous Disord. 2006;23(3):223-228.
3.
Doyle DJ, Fanning NF, Silke CS, et al. Wegener’s Granulomatosis of the Main Pulmonary Arteries: Imaging Findings. Clin Radiol. 2003;58(4):329-331. doi:10.1016/S0009-9260(02)00517-2.
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1.
ACCEPTED MANUSCRIPT
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Figure 1. Ventilation-perfusion (VQ) scan and pulmonary angiography findings. (A) Baseline VQ scan revealed multiple perfusion defects consistent with thromboembolic disease. (B) Pulmonary angiography (right and left anterior views) ruled out chronic thromboembolic disease but demonstrated poor peripheral perfusion with a typical “dead tree” aspect.
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ACCEPTED MANUSCRIPT
