Unusual presentation of more common disease/injury
CASE REPORT
Pericardial mass in a patient with rheumatoid arthritis Mohammad Al-Ani,1 Michelle Weber,2 David Winchester,3 Matthew Kosboth4 1
Department of Internal Medicine, University of Florida, Gainesville, Florida, USA 2 Department of Pathology, Malcom Randall VAMC, NF/SGVHS, Gainesville, Florida, USA 3 Department of Internal Medicine – Division of Cardiology, University of Florida, Gainesville, Florida, USA 4 Department of Internal Medicine – Division of Rheumatology, Malcom Randall VAMC, NF/SGVHS, Gainesville, Florida, USA Correspondence to Dr Mohammad Al-Ani, malani@ufl.edu Accepted 11 May 2015
SUMMARY A 65-year-old man presented with long-standing rheumatoid arthritis (RA), severe fatigue and mild arthritis of metacarpophalaneal joints. Physical examination revealed S3, II/IV decrescendo diastolic murmur and 2+ LL oedema. Anticyclic citrullinated peptide antibodies were >250 units. Echocardiogram showed an 8 cm pericardial mass with no atrial or ventricular collapse and mild to moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior and inferior heart borders, with compression on right cardiac structures and the left ventricle. CT-guided biopsy demonstrated fibrinous material without granulomas or infection. Fatigue did not improve on immunosuppression with low-dose prednisone and leflunamide. Cardiac tamponade was confirmed by heart catheterisation and the mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and, 4 years later, he remains asymptomatic cardiac wise. This case highlights the clinical significance of pericardial disease in RA and its response to therapy.
BACKGROUND Early in the 1900s, rheumatoid arthritis (RA) and rheumatic fever were perceived as different manifestations of a common pathology because of similar heart findings in autopsies.1 Cardiac manifestations of RA can be classified pathophysiologically into: coronary artery disease, heart failure, arrhythmias, endocarditis, myocaditis and pericarditis.2–5 The pericardium is the most frequently involved cardiac structure in RA, and the prevalence of pericarditis can be up to 30%, depending on the diagnostic technique (echocardiography vs postmortem examination) used. The disease, however, is most commonly subclinical but can present as acute pericarditis and be recurrent.6 Haemodynamically significant RA cardiac disease is seldom confined to the pericardium and hence is associated with a worse outcome. On the other hand, patients with RA are susceptible to a myriad of other conditions that can affect the heart directly and indirectly, including endothelial dysfunction, infections and lymphomas. To cite: Al-Ani M, Weber M, Winchester D, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2015209861
CASE PRESENTATION Our patient is a 65-year-old Caucasian man with a history of RA, fibromyalgia, depression, nephrolithiasis and ischemic stroke without residual deficits, who presented to rheumatology outpatient clinic with a 6-month history of morning stiffness
lasting for 3 h, severe fatigue and mild to moderate pain in proximal interphalangeal and wrist joints bilaterally. The patient denied cough, dyspnoea, orthopnoea, chest pain, syncope, palpitation, lower limb swelling, claudication, fever/chills or history of tuberculosis by infection or exposure. He does not have a history of cardiovascular disease. Medical history includes RA, diagnosed 15 years prior, which was largely limited to small hand joints and wrists. He was initially treated with methotrexate and, 4 years ago, switched to auranofin (Gold) because he developed rheumatoid pleural effusion, and most recently treated with non-steroidal anti-inflammatory drugs and prednisone 10 mg daily. The effusion was recurrent and consistently right sided, and was eventually treated with decortication and pleurodesis 9 months before the current presentation. The patient has not had relevant environmental exposure to toxic or infectious agents. Family history was negative for neoplasia. On physical examination, the patient appeared cachectic, not in distress and vitals were within normal limits. His neck had neither lymphadenopathy nor jugular venous distention. Lungs were clear to auscultation with diminished air entry to the right lower zone. Cardiac examination revealed left parasternal heave, normal S1 and S2, left-sided S3 and II/IV decrescendo diastolic murmur, heard best at the left lower sternal border, suggesting aortic regurgitation. Durozier’s sign was positive. The jugular veins were distended and the liver was pulsatile without positive hepatojugular reflux. There was no dilated superficial veins on the chest or abdomen. Pitting lower limb oedema of 2+ was noted bilaterally. All joints were free of inflammatory signs except for boggy non-tender metacarpophalangeal joints bilaterally. Both wrists were subluxed with limited range of motion. There was one subcutaneous rheumatoid nodule over the left wrist.
INVESTIGATIONS Laboratory data revealed mild microcytic anaemia and normal hepatic, renal and thyroid functions. Erythrocyte sedimentation rate 23 mm/h, anticyclic citrullinated peptide (anti-CCP) antibodies >250 units, rheumatoid factor titre 1:4 and antinuclear antibodies were negative. Tuberculin skin test was negative. Transthoracic echocardiogram showed a mass impinging the right ventricle that was best visualised on apical four-chamber view (video 1). The mass seemed heterogeneous but it was difficult to discern if it was an intrapericardial
Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
1
Unusual presentation of more common disease/injury
Video 1 Apical four-chamber view of transthoracic echocardiogram. Notice the mass compressing the right ventricle causing complete collapse of the chamber at end diastole. or a mediastinal mass compressing the heart. There was also mild to moderate aortic regurgitation with mild mitral regurgitation and no pericardial effusion was detected. Inferior vena cava (IVC) diameter was 2.7 cm with less than 10% collapse on inspiration (video 2). The tricuspid valve was normal but Doppler signal was suboptimal given the distortion of the right ventricular geometry. MRI with gadolinium contrast showed a complex loculated pericardial fluid collection, positioning inferiorly and extending from the apex to the base. The fluid was surrounded by a thick rind and was adjacent to the right atrioventricular groove causing pressure on all right cardiac structures and the left ventricle. IVC and hepatic veins were dilated secondary to constrictive physiology on the right atrium. Additionally, there was a posterior right pleural collection with the same features of complex content and thick wall. No myocardial enhancement was seen, making associated infiltrative cardiomyopathy unlikely (figure 1). A CT-guided biopsy of the lesion confirmed its fibrinous exudative nature, without any evidence of lymphomatous, granulomatous or infectious processes.
DIFFERENTIAL DIAGNOSIS Given the patient’s immunosuppression, the subacute presentation, the recurring pleural effusion and the uncontrolled autoimmune syndrome, concerns were focused on opportunistic
Video 2 Subcostal inferior vena cava view of transthoracic echocardiogram. Notice the distention of the inferior vena cava and its lack of pulsality with respiration.
2
Figure 1 Cardiac MRI, T2-weighted images demonstrating the pericardial lesion (asterisks) in coronal (A), and sagittal (B) and cross (C) sections. Note the heterogeneity of the lesion and its right, anterior and inferior extension. Section (C) best shows the lesion compressing the right ventricle and right atrium. There is also distortion of the normally more circular shape of the left ventricle.
Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
Unusual presentation of more common disease/injury infections such as typical or atypical tuberculosis, metastatic neoplasia and lymphoma. Biopsy did not show evidence of malignancy or infection. Also, there was absence of palisading histiocytes, which are characteristic of rheumatoid nodules. Chronic pericarditis was the most plausible diagnosis, although others could not be completely ruled out based on a tissue sample from only one part of the lesion.
TREATMENT At that point, the patient’s symptoms of fatigue and dyspnoea on exertion were not severe enough to justify invasive measures and the therapeutic strategy was to intensify his immunosuppressive regimen to induce RA remission while monitoring the pericardial lesion clinically. Prednisone 10 mg was continued and leflunamide was started along with non-steroidal antiinflammatory medications as needed for joint pain. Three months later, despite improvement in morning stiffness, he was still fatigued and declined functionally to New York Heart Association (NYHA) class IIIb, with platypnoea. On re-examination, he was found to have elevation of jugular venous pressure to above the mandibular angle in the sitting position with the other previous findings still present. Repeat CT revealed peripheral calcification of the pericardial lesion, no change in size of either pleural or pericardial collections, dilation of the superior and inferior vena cava and hepatic veins with retrograde leak of contrast to the liver (figure 2). Tamponade physiology was suspected and the patient underwent left and right cardiac catheterisations (table 1) to fully assess the haemodynamics. Coronary angiogram was free of any obstructive lesions. The cardiothoracic surgery team was consulted and an elective open excision of the pericardial mass was pursued with
Table 1 Diagnostic left and right cardiac catheterisation measurement results RA mean pressure RV pressures PA pressure PCWP Cardiac output Cardiac index
16 28/18 (23) 28/16 (22) 16 2.5 L/min 1.2 L/min/m2
Aortic pressures LVESP LVEDP Ejection fraction HR PVR
100/70 100 16 60% 93 2.8 Wood’s units
Notice the equilibration of intracardiac pressures (PCWP, LVEDP, and RV and RA diastolic pressures) suggesting tamponade physiology. Cardiac output was measured via thermodilution. Pressures are expressed in mm Hg. HR, heart rate; LVEDP, left ventricular end diastolic pressure; LVESP, left ventricular end systolic pressure; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RA, right atrium; RV, right ventricle.
partial pericardiectomy. The mass was adherent to the right atrium, left ventricle and aortic root, containing old blood and what appeared to be a recent thrombus. All scar tissue was dissected from the epicardium except for a small area over the left ventricle near the anterior descending–diagonal artery system. Frozen sections were taken for microscopy, which revealed fibrinous material. Subsequent histopathological examination indicated thickening of the pericardium by dense sclerotic collagen with foci of lymphoplasmacytic chronic inflammation and hemosiderin deposition, which is consistent with chronic fibrinous pericarditis. In addition, there were a few organised blood clots and foci of granulation tissue. No granulomata were identified (figure 3).
OUTCOME AND FOLLOW-UP The patient recovered from surgery uneventfully with dramatic improvement of his symptoms. One month later, he was walking one mile per day; whereas simply bending over to tie his shoes previously required 5 min of rest. Our patient was not treated with any scheduled cardiac medications before or after surgery. Follow-up transthoracic echocardiogram showed mild mitral and aortic regurgitation and no pericardial disease. The small pleural effusion detected on CT remained stable throughout the above described timeline. After 4 years, the patient remains completely asymptomatic from a cardiac standpoint and his RA disease is well controlled.
DISCUSSION
Figure 2 Cardiac CT with IV contrast. (A) Shows reverse contrast constitution of azygous vein (arrows). (B) Shows reverse constitution of hepatic vein and sublobular veins (arrows). Both signs indicate elevated right heart pressures. Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
We present a case of uncontrolled RA in a male patient with no cardiac history, who presented with extreme fatigue and signs of right-sided cardiac compression and aortic regurgitation. This was also suggested initially by physical examination, and later confirmed via right heart catheterisation showing elevated right atrial pressure. The diastolic murmur was attributed to the aortic regurgitation detected by echocardiogram, which also indicated mild MR, although no systolic murmur was clinically appreciated. These valvular phenomena were likely related to extrinsic compression on the pericardium or attachment of the lesion to the aortic root and left ventricle, or both, because they were partially reversed after the procedure. Cardiac MRI helped to better characterise the anatomy and to exclude accompanying myocardial disease. Suppressing RA disease activity did not translate into clinical improvement in our patient, and more specific heart failure manifestations were detected on follow-up examination. Acute pericarditis usually responds to immunosuppression, unlike chronic or nodular pericardial disease. Given the severe impact 3
Unusual presentation of more common disease/injury chronic inflammatory infiltration with the recurrent effusions eventually organising into this mass. The deterioration over a few months and the surgical finding of a recent clot point to the possibility of intralesional bleeding during the biopsy procedure causing rapid expansion of the lesion and tipping the balance towards acute decompensation. Earlier reports described RA-related pericarditis in many instances. However, fewer than 10% of patients with severe RA show clinical signs of pericarditis. When seen, pericarditis is more common among males with nodular and erosive rheumatism.8 9 Pericardial effusions may also be seen in echocardiographic studies of patients with RA; constrictive pericarditis may develop and is often clinically silent.3 Almost all patients with pericardial disease have high titres of rheumatoid factor and in half of the instances have subcutaneous nodules. Although the pathophysiology of pericardial disease in RA has not been elucidated, the disease has been linked to RA activity, and our patient had evidence of prolonged uncontrolled disease course as evident by the severe joint deformities and the level of anti-CCP antibodies. Hara et al,10 in their prospective investigation, demonstrated that clinically evident pericardial involvement is associated with high mortality, particularly during the first year of follow-up. This poor prognosis may be due to the fact that symptomatic patients tend to have multifocal nodular disease in the heart, involving the myocardium and/or valvular leaflets. Rodriguez Monserrate et al11 described the only isolated rheumatoid pericardial nodule reported in the literature we could find. That patient, similar to ours, had a rapidly growing nodule that compressed the right ventricle, causing symptomatology that was alleviated by surgical resection. Two other cases were also described but both expired within weeks after presentation. In both reports, associated cardiac pathology was present; specifically, recurrent pericardial effusion in one case and intracardiac nodules in the other.12 13 Microscopically,
Patient’s perspective I was getting progressively sicker and reached a point where I would get winded tying my shoelace. Changing medications did not help me much. My legs were getting swollen and I had to sleep on a chair. Surgery made a huge difference for me. The next day I was walking and felt great relief. Now I am able to work at my yard, drive, shop and visit friends. Also, my arthritis has much improved. I am very grateful to my doctors. Figure 3 Histopathology examination of the excised pericardial lesion. (A) Low power view: note the dense fibrous thickening of the pericardium with foci of chronic inflammation. (B) High power view: there is chronic lymphoplasmacytic inflammatory infiltrate within the pericardium. (C) Oil immersion view: showing dense sclerotic collagen with hemosiderin deposition that is presumed to be a caused by intralesional haemorrhage from the prior biopsy. on the patient’s quality of life, the rather rapid deterioration, and requirement of a major surgery should the pericardial lesion be the culprit, left and right cardiac catheterisations were performed to definitively evaluate the cardiac haemodynamics and to screen for silent myocardial ischaemia, which is more prevalent in RA patients and can significantly influence further management.7 Ultimately, the pericardial lesion was excised and the patient had sustained relief. The patient likely has had recurrent subclinical pericarditis causing pericardial fibrosis and 4
Learning points ▸ Lone subclinical pericarditis without accompanying myocardial involvement can occur in rheumatoid arthritis (RA) patients. ▸ Anticyclic citrullinated peptide antibodies can be a better marker for RA pericardial disease than rheumatoid factor. ▸ With limited evidence, the prognosis of pericardial rheumatoid arthritis disease appears to be good in the absence of myocardial involvement. ▸ Surgery may be necessary for the management of RA-related pericardial nodules. ▸ Not every complaint of fatigue in a patient with previously diagnosed fibromyalgia is due to fibromyalgia. Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
Unusual presentation of more common disease/injury rheumatoid nodules have a centre of fibrinoid necrosis surrounded by a prominent rim of epithelioid histiocytes, and numerous lymphocytes and plasma cells.14 However, in the presented case, histopathological examination of the excised tissue was consistent with chronic fibrinous pericarditis.
2 3 4 5
Acknowledgements The authors thank Dr Anita Wokhlu and Dr Alexandra Lucas for their help in obtaining and analysing images related to this case. Contributors MA-A interviewed the patient, reviewed the literature, collected data and wrote the first draft of the manuscript. DW analysed cardiac studies, revised and edited the manuscript. MW prepared and examined pathology slides and produced images. Provided description of pathological findings compared to expected features. KM first diagnosed the patient with heart failure, managed his rheumatoid arthritis disease, followed the case longitudinally, contributed to the first and final versions of this manuscript, and provided supervision to the first author.
6 7 8 9 10
Competing interests None declared. Patient consent Obtained.
11
Provenance and peer review Not commissioned; externally peer reviewed. 12
REFERENCES 1
Rosenberg EF, Bishop LF Jr, Weintraub HJ, et al. Cardiac lesions in rheumatoid arthritis; a summary of recent developments and a bedside study of patients and controls. Arch Intern Med (Chic) 1950;85:751–64.
13 14
Mellana WM, Aronow WS, Palaniswamy C, et al. Rheumatoid arthritis: cardiovascular manifestations, pathogenesis, and therapy. Curr Pharm Des 2012;18:1450–6. Salmon JE, Roman MJ. Cardiovascular involvement in general medical conditions. Circulation 2007;116:2346–55. Kaplan MJ. Cardiovascularcomplicationsofrheumatoidarthritis: assessment, prevention,andtreatment. Rheum Dis Clin North Am 2010;36:405–23. Turiel M, Sitia S, Atzeni F, et al. The heart in rheumatoid arthritis. Autoimmun Rev 2010;9:414–18. Corrao S, Sallì L, Arnone S, et al. Cardiac involvement in rheumatoid arthritis: evidence of silent heart disease. Eur Heart J 1995;16:253–6. Dala AG, Ibrahim WA, Taha AA, et al. Is silent ischemic heart disease evident in rheumatoid arthritis patients? Life Sci J 2012;9:927–34. Gordon DA, Stein JL, Broder I. The extraarticular features of rheumatoid arthritis. Am J Med 1973;54:445–52. Kelly CA, Bourke JP, Malcolm A, et al. Chronic pericardial disease in patients with rheumatoid arthritis: a longitudinal study. Q J Med 1990;75:461–70. Hara KS, Ballard DJ, Ilstrup DM, et al. Rheumatoid pericarditis: clinical features and survival. Medicine 1990;69:81–91. Rodriguez Monserrate CP, del Rio JR, López López Y, et al. Rheumatoid pericardial mass producing right ventricle inflow tract restriction: a case report. Bol Asoc Med P R 2012;104:47–9. Ojeda VJ, Stuckey BG, Owen ET, et al. Cardiac rheumatoid nodules. Med J Aust 1986;144:92–3. Bhat P, Chandrasekaran B, Barnes E. Cardiac compression from a rheumatoid pericardial mass. Heart 2006;92:1337. Kumar V, Abbas AK, Fausto N, et al. Robbins and cotran pathologic basis of disease. 8th edn. Philadelphia, PA: Saunders Elsevier, 2010.
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Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
5
CASE REPORT
Pericardial mass in a patient with rheumatoid arthritis Mohammad Al-Ani,1 Michelle Weber,2 David Winchester,3 Matthew Kosboth4 1
Department of Internal Medicine, University of Florida, Gainesville, Florida, USA 2 Department of Pathology, Malcom Randall VAMC, NF/SGVHS, Gainesville, Florida, USA 3 Department of Internal Medicine – Division of Cardiology, University of Florida, Gainesville, Florida, USA 4 Department of Internal Medicine – Division of Rheumatology, Malcom Randall VAMC, NF/SGVHS, Gainesville, Florida, USA Correspondence to Dr Mohammad Al-Ani, malani@ufl.edu Accepted 11 May 2015
SUMMARY A 65-year-old man presented with long-standing rheumatoid arthritis (RA), severe fatigue and mild arthritis of metacarpophalaneal joints. Physical examination revealed S3, II/IV decrescendo diastolic murmur and 2+ LL oedema. Anticyclic citrullinated peptide antibodies were >250 units. Echocardiogram showed an 8 cm pericardial mass with no atrial or ventricular collapse and mild to moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior and inferior heart borders, with compression on right cardiac structures and the left ventricle. CT-guided biopsy demonstrated fibrinous material without granulomas or infection. Fatigue did not improve on immunosuppression with low-dose prednisone and leflunamide. Cardiac tamponade was confirmed by heart catheterisation and the mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and, 4 years later, he remains asymptomatic cardiac wise. This case highlights the clinical significance of pericardial disease in RA and its response to therapy.
BACKGROUND Early in the 1900s, rheumatoid arthritis (RA) and rheumatic fever were perceived as different manifestations of a common pathology because of similar heart findings in autopsies.1 Cardiac manifestations of RA can be classified pathophysiologically into: coronary artery disease, heart failure, arrhythmias, endocarditis, myocaditis and pericarditis.2–5 The pericardium is the most frequently involved cardiac structure in RA, and the prevalence of pericarditis can be up to 30%, depending on the diagnostic technique (echocardiography vs postmortem examination) used. The disease, however, is most commonly subclinical but can present as acute pericarditis and be recurrent.6 Haemodynamically significant RA cardiac disease is seldom confined to the pericardium and hence is associated with a worse outcome. On the other hand, patients with RA are susceptible to a myriad of other conditions that can affect the heart directly and indirectly, including endothelial dysfunction, infections and lymphomas. To cite: Al-Ani M, Weber M, Winchester D, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2015209861
CASE PRESENTATION Our patient is a 65-year-old Caucasian man with a history of RA, fibromyalgia, depression, nephrolithiasis and ischemic stroke without residual deficits, who presented to rheumatology outpatient clinic with a 6-month history of morning stiffness
lasting for 3 h, severe fatigue and mild to moderate pain in proximal interphalangeal and wrist joints bilaterally. The patient denied cough, dyspnoea, orthopnoea, chest pain, syncope, palpitation, lower limb swelling, claudication, fever/chills or history of tuberculosis by infection or exposure. He does not have a history of cardiovascular disease. Medical history includes RA, diagnosed 15 years prior, which was largely limited to small hand joints and wrists. He was initially treated with methotrexate and, 4 years ago, switched to auranofin (Gold) because he developed rheumatoid pleural effusion, and most recently treated with non-steroidal anti-inflammatory drugs and prednisone 10 mg daily. The effusion was recurrent and consistently right sided, and was eventually treated with decortication and pleurodesis 9 months before the current presentation. The patient has not had relevant environmental exposure to toxic or infectious agents. Family history was negative for neoplasia. On physical examination, the patient appeared cachectic, not in distress and vitals were within normal limits. His neck had neither lymphadenopathy nor jugular venous distention. Lungs were clear to auscultation with diminished air entry to the right lower zone. Cardiac examination revealed left parasternal heave, normal S1 and S2, left-sided S3 and II/IV decrescendo diastolic murmur, heard best at the left lower sternal border, suggesting aortic regurgitation. Durozier’s sign was positive. The jugular veins were distended and the liver was pulsatile without positive hepatojugular reflux. There was no dilated superficial veins on the chest or abdomen. Pitting lower limb oedema of 2+ was noted bilaterally. All joints were free of inflammatory signs except for boggy non-tender metacarpophalangeal joints bilaterally. Both wrists were subluxed with limited range of motion. There was one subcutaneous rheumatoid nodule over the left wrist.
INVESTIGATIONS Laboratory data revealed mild microcytic anaemia and normal hepatic, renal and thyroid functions. Erythrocyte sedimentation rate 23 mm/h, anticyclic citrullinated peptide (anti-CCP) antibodies >250 units, rheumatoid factor titre 1:4 and antinuclear antibodies were negative. Tuberculin skin test was negative. Transthoracic echocardiogram showed a mass impinging the right ventricle that was best visualised on apical four-chamber view (video 1). The mass seemed heterogeneous but it was difficult to discern if it was an intrapericardial
Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
1
Unusual presentation of more common disease/injury
Video 1 Apical four-chamber view of transthoracic echocardiogram. Notice the mass compressing the right ventricle causing complete collapse of the chamber at end diastole. or a mediastinal mass compressing the heart. There was also mild to moderate aortic regurgitation with mild mitral regurgitation and no pericardial effusion was detected. Inferior vena cava (IVC) diameter was 2.7 cm with less than 10% collapse on inspiration (video 2). The tricuspid valve was normal but Doppler signal was suboptimal given the distortion of the right ventricular geometry. MRI with gadolinium contrast showed a complex loculated pericardial fluid collection, positioning inferiorly and extending from the apex to the base. The fluid was surrounded by a thick rind and was adjacent to the right atrioventricular groove causing pressure on all right cardiac structures and the left ventricle. IVC and hepatic veins were dilated secondary to constrictive physiology on the right atrium. Additionally, there was a posterior right pleural collection with the same features of complex content and thick wall. No myocardial enhancement was seen, making associated infiltrative cardiomyopathy unlikely (figure 1). A CT-guided biopsy of the lesion confirmed its fibrinous exudative nature, without any evidence of lymphomatous, granulomatous or infectious processes.
DIFFERENTIAL DIAGNOSIS Given the patient’s immunosuppression, the subacute presentation, the recurring pleural effusion and the uncontrolled autoimmune syndrome, concerns were focused on opportunistic
Video 2 Subcostal inferior vena cava view of transthoracic echocardiogram. Notice the distention of the inferior vena cava and its lack of pulsality with respiration.
2
Figure 1 Cardiac MRI, T2-weighted images demonstrating the pericardial lesion (asterisks) in coronal (A), and sagittal (B) and cross (C) sections. Note the heterogeneity of the lesion and its right, anterior and inferior extension. Section (C) best shows the lesion compressing the right ventricle and right atrium. There is also distortion of the normally more circular shape of the left ventricle.
Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
Unusual presentation of more common disease/injury infections such as typical or atypical tuberculosis, metastatic neoplasia and lymphoma. Biopsy did not show evidence of malignancy or infection. Also, there was absence of palisading histiocytes, which are characteristic of rheumatoid nodules. Chronic pericarditis was the most plausible diagnosis, although others could not be completely ruled out based on a tissue sample from only one part of the lesion.
TREATMENT At that point, the patient’s symptoms of fatigue and dyspnoea on exertion were not severe enough to justify invasive measures and the therapeutic strategy was to intensify his immunosuppressive regimen to induce RA remission while monitoring the pericardial lesion clinically. Prednisone 10 mg was continued and leflunamide was started along with non-steroidal antiinflammatory medications as needed for joint pain. Three months later, despite improvement in morning stiffness, he was still fatigued and declined functionally to New York Heart Association (NYHA) class IIIb, with platypnoea. On re-examination, he was found to have elevation of jugular venous pressure to above the mandibular angle in the sitting position with the other previous findings still present. Repeat CT revealed peripheral calcification of the pericardial lesion, no change in size of either pleural or pericardial collections, dilation of the superior and inferior vena cava and hepatic veins with retrograde leak of contrast to the liver (figure 2). Tamponade physiology was suspected and the patient underwent left and right cardiac catheterisations (table 1) to fully assess the haemodynamics. Coronary angiogram was free of any obstructive lesions. The cardiothoracic surgery team was consulted and an elective open excision of the pericardial mass was pursued with
Table 1 Diagnostic left and right cardiac catheterisation measurement results RA mean pressure RV pressures PA pressure PCWP Cardiac output Cardiac index
16 28/18 (23) 28/16 (22) 16 2.5 L/min 1.2 L/min/m2
Aortic pressures LVESP LVEDP Ejection fraction HR PVR
100/70 100 16 60% 93 2.8 Wood’s units
Notice the equilibration of intracardiac pressures (PCWP, LVEDP, and RV and RA diastolic pressures) suggesting tamponade physiology. Cardiac output was measured via thermodilution. Pressures are expressed in mm Hg. HR, heart rate; LVEDP, left ventricular end diastolic pressure; LVESP, left ventricular end systolic pressure; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RA, right atrium; RV, right ventricle.
partial pericardiectomy. The mass was adherent to the right atrium, left ventricle and aortic root, containing old blood and what appeared to be a recent thrombus. All scar tissue was dissected from the epicardium except for a small area over the left ventricle near the anterior descending–diagonal artery system. Frozen sections were taken for microscopy, which revealed fibrinous material. Subsequent histopathological examination indicated thickening of the pericardium by dense sclerotic collagen with foci of lymphoplasmacytic chronic inflammation and hemosiderin deposition, which is consistent with chronic fibrinous pericarditis. In addition, there were a few organised blood clots and foci of granulation tissue. No granulomata were identified (figure 3).
OUTCOME AND FOLLOW-UP The patient recovered from surgery uneventfully with dramatic improvement of his symptoms. One month later, he was walking one mile per day; whereas simply bending over to tie his shoes previously required 5 min of rest. Our patient was not treated with any scheduled cardiac medications before or after surgery. Follow-up transthoracic echocardiogram showed mild mitral and aortic regurgitation and no pericardial disease. The small pleural effusion detected on CT remained stable throughout the above described timeline. After 4 years, the patient remains completely asymptomatic from a cardiac standpoint and his RA disease is well controlled.
DISCUSSION
Figure 2 Cardiac CT with IV contrast. (A) Shows reverse contrast constitution of azygous vein (arrows). (B) Shows reverse constitution of hepatic vein and sublobular veins (arrows). Both signs indicate elevated right heart pressures. Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
We present a case of uncontrolled RA in a male patient with no cardiac history, who presented with extreme fatigue and signs of right-sided cardiac compression and aortic regurgitation. This was also suggested initially by physical examination, and later confirmed via right heart catheterisation showing elevated right atrial pressure. The diastolic murmur was attributed to the aortic regurgitation detected by echocardiogram, which also indicated mild MR, although no systolic murmur was clinically appreciated. These valvular phenomena were likely related to extrinsic compression on the pericardium or attachment of the lesion to the aortic root and left ventricle, or both, because they were partially reversed after the procedure. Cardiac MRI helped to better characterise the anatomy and to exclude accompanying myocardial disease. Suppressing RA disease activity did not translate into clinical improvement in our patient, and more specific heart failure manifestations were detected on follow-up examination. Acute pericarditis usually responds to immunosuppression, unlike chronic or nodular pericardial disease. Given the severe impact 3
Unusual presentation of more common disease/injury chronic inflammatory infiltration with the recurrent effusions eventually organising into this mass. The deterioration over a few months and the surgical finding of a recent clot point to the possibility of intralesional bleeding during the biopsy procedure causing rapid expansion of the lesion and tipping the balance towards acute decompensation. Earlier reports described RA-related pericarditis in many instances. However, fewer than 10% of patients with severe RA show clinical signs of pericarditis. When seen, pericarditis is more common among males with nodular and erosive rheumatism.8 9 Pericardial effusions may also be seen in echocardiographic studies of patients with RA; constrictive pericarditis may develop and is often clinically silent.3 Almost all patients with pericardial disease have high titres of rheumatoid factor and in half of the instances have subcutaneous nodules. Although the pathophysiology of pericardial disease in RA has not been elucidated, the disease has been linked to RA activity, and our patient had evidence of prolonged uncontrolled disease course as evident by the severe joint deformities and the level of anti-CCP antibodies. Hara et al,10 in their prospective investigation, demonstrated that clinically evident pericardial involvement is associated with high mortality, particularly during the first year of follow-up. This poor prognosis may be due to the fact that symptomatic patients tend to have multifocal nodular disease in the heart, involving the myocardium and/or valvular leaflets. Rodriguez Monserrate et al11 described the only isolated rheumatoid pericardial nodule reported in the literature we could find. That patient, similar to ours, had a rapidly growing nodule that compressed the right ventricle, causing symptomatology that was alleviated by surgical resection. Two other cases were also described but both expired within weeks after presentation. In both reports, associated cardiac pathology was present; specifically, recurrent pericardial effusion in one case and intracardiac nodules in the other.12 13 Microscopically,
Patient’s perspective I was getting progressively sicker and reached a point where I would get winded tying my shoelace. Changing medications did not help me much. My legs were getting swollen and I had to sleep on a chair. Surgery made a huge difference for me. The next day I was walking and felt great relief. Now I am able to work at my yard, drive, shop and visit friends. Also, my arthritis has much improved. I am very grateful to my doctors. Figure 3 Histopathology examination of the excised pericardial lesion. (A) Low power view: note the dense fibrous thickening of the pericardium with foci of chronic inflammation. (B) High power view: there is chronic lymphoplasmacytic inflammatory infiltrate within the pericardium. (C) Oil immersion view: showing dense sclerotic collagen with hemosiderin deposition that is presumed to be a caused by intralesional haemorrhage from the prior biopsy. on the patient’s quality of life, the rather rapid deterioration, and requirement of a major surgery should the pericardial lesion be the culprit, left and right cardiac catheterisations were performed to definitively evaluate the cardiac haemodynamics and to screen for silent myocardial ischaemia, which is more prevalent in RA patients and can significantly influence further management.7 Ultimately, the pericardial lesion was excised and the patient had sustained relief. The patient likely has had recurrent subclinical pericarditis causing pericardial fibrosis and 4
Learning points ▸ Lone subclinical pericarditis without accompanying myocardial involvement can occur in rheumatoid arthritis (RA) patients. ▸ Anticyclic citrullinated peptide antibodies can be a better marker for RA pericardial disease than rheumatoid factor. ▸ With limited evidence, the prognosis of pericardial rheumatoid arthritis disease appears to be good in the absence of myocardial involvement. ▸ Surgery may be necessary for the management of RA-related pericardial nodules. ▸ Not every complaint of fatigue in a patient with previously diagnosed fibromyalgia is due to fibromyalgia. Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
Unusual presentation of more common disease/injury rheumatoid nodules have a centre of fibrinoid necrosis surrounded by a prominent rim of epithelioid histiocytes, and numerous lymphocytes and plasma cells.14 However, in the presented case, histopathological examination of the excised tissue was consistent with chronic fibrinous pericarditis.
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Acknowledgements The authors thank Dr Anita Wokhlu and Dr Alexandra Lucas for their help in obtaining and analysing images related to this case. Contributors MA-A interviewed the patient, reviewed the literature, collected data and wrote the first draft of the manuscript. DW analysed cardiac studies, revised and edited the manuscript. MW prepared and examined pathology slides and produced images. Provided description of pathological findings compared to expected features. KM first diagnosed the patient with heart failure, managed his rheumatoid arthritis disease, followed the case longitudinally, contributed to the first and final versions of this manuscript, and provided supervision to the first author.
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Competing interests None declared. Patient consent Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed. 12
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Mellana WM, Aronow WS, Palaniswamy C, et al. Rheumatoid arthritis: cardiovascular manifestations, pathogenesis, and therapy. Curr Pharm Des 2012;18:1450–6. Salmon JE, Roman MJ. Cardiovascular involvement in general medical conditions. Circulation 2007;116:2346–55. Kaplan MJ. Cardiovascularcomplicationsofrheumatoidarthritis: assessment, prevention,andtreatment. Rheum Dis Clin North Am 2010;36:405–23. Turiel M, Sitia S, Atzeni F, et al. The heart in rheumatoid arthritis. Autoimmun Rev 2010;9:414–18. Corrao S, Sallì L, Arnone S, et al. Cardiac involvement in rheumatoid arthritis: evidence of silent heart disease. Eur Heart J 1995;16:253–6. Dala AG, Ibrahim WA, Taha AA, et al. Is silent ischemic heart disease evident in rheumatoid arthritis patients? Life Sci J 2012;9:927–34. Gordon DA, Stein JL, Broder I. The extraarticular features of rheumatoid arthritis. Am J Med 1973;54:445–52. Kelly CA, Bourke JP, Malcolm A, et al. Chronic pericardial disease in patients with rheumatoid arthritis: a longitudinal study. Q J Med 1990;75:461–70. Hara KS, Ballard DJ, Ilstrup DM, et al. Rheumatoid pericarditis: clinical features and survival. Medicine 1990;69:81–91. Rodriguez Monserrate CP, del Rio JR, López López Y, et al. Rheumatoid pericardial mass producing right ventricle inflow tract restriction: a case report. Bol Asoc Med P R 2012;104:47–9. Ojeda VJ, Stuckey BG, Owen ET, et al. Cardiac rheumatoid nodules. Med J Aust 1986;144:92–3. Bhat P, Chandrasekaran B, Barnes E. Cardiac compression from a rheumatoid pericardial mass. Heart 2006;92:1337. Kumar V, Abbas AK, Fausto N, et al. Robbins and cotran pathologic basis of disease. 8th edn. Philadelphia, PA: Saunders Elsevier, 2010.
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Al-Ani M, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209861
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