LETTER TO THE EDITOR
Cardiac Tamponade in a Patient With Mixed Connective Tissue Disease To the Editor: ixed connective tissue disease (MCTD) is an autoimmune disease that presents with clinical features of systemic lupus erythematosus (SLE), scleroderma, and inflammatory muscle disease and the presence of anti–ribonucleoprotein (RNP) antibodies. It can affect a variety of organ/systems, including the heart. Pericarditis, with or without effusion, is the most common cardiac manifestation followed by mitral valve prolapse and pulmonary hypertension.1–3 However, cardiac tamponade is very unusual. Here, we describe a case of cardiac tamponade in a woman with MCTD and provide a review of other reported cases. A 59-year-old Puerto Rican woman presented with a 3-month history of tiredness, high-grade fever, anorexia, weight loss (20 lb), hair loss, oral ulcers, mild sicca symptoms, Raynaud phenomenon, arthralgias, myalgias, muscle weakness, dry cough, and chest discomfort. She had a medical history of gastroesophageal reflux disease and bronchial asthma. She was taking ibuprofen for arthralgias. She had no history of tobacco or alcohol use. Surgical history was remarkable for right carpal tunnel surgery. She had a cousin diagnosed with SLE, but the remainder of her family history was noncontributory. On physical examination, she had a body mass index of 21.9 kg/m2 with normal vital signs. She had synovitis of the
M
metacarpophalangeal joints, wrists, elbows, ankles, and metatarsophalangeal joints bilaterally. She had symmetric lower-extremity proximal muscle weakness (4/5). The remainder of the examination was unremarkable. Laboratory tests showed a white blood cell count of 6.9 109/L, hemoglobin of 11.1 g/dL and platelet count of 329 109/L. The reticulocyte count was mildly increased at 1.6%. Peripheral blood smear did not show spherocytes or schistocytes. Coombs test was negative. The Westergren erythrocyte sedimentation rate was markedly elevated at 128 mm/h as well as C-reactive protein levels at 60.8 mg/L. Serum electrolytes, renal and hepatic profiles, muscle enzymes, and coagulation tests were normal. Antinuclear antibodies (ANAs) were elevated at 1:2560 with speckled pattern. Anti–ribonucleoprotein antibodies were also markedly increased (>100 U/mL). Rheumatoid factor (14.1 U/mL) and anti-Ro antibodies (>8 U/mL) were detected. Anti-dsDNA, anti-Smith (Sm), anti–citrullinated peptide, antimyeloperoxidase, anti–proteinase 3, and anti-La antibodies were negative. A chest radiograph did not show abnormalities. Bilateral hand and wrist sonogram showed synovial hypertrophy of the metacarpophalangeal joints bilaterally. No erosions were seen. Minor salivary gland biopsy did not show inflammatory changes. Mixed connective tissue disease was diagnosed, and the patient was started on prednisone 20 mg daily and hydroxychloroquine 200 mg twice daily. One month later, she developed worsening dyspnea on exertion associated with
palpitations, chest pain, and lower-extremity swelling. She underwent outpatient echocardiography that revealed a moderate pericardial effusion with right atrial collapse. She was referred for hospitalization. Upon admission, she was afebrile with a blood pressure of 102/60 mm Hg; her heart rate was 86 beats/min, and the respiratory rate was 16 breaths/min. Examination was remarkable for lower-extremity pitting edema. There was no pericardial rub. Chest radiograph showed cardiomegaly. An electrocardiogram revealed low-voltage complexes without ST-segment changes. A repeat echocardiogram confirmed a moderate pericardial effusion with right atrial diastolic collapse, minimal mitral and aortic valve regurgitation, and a minimally decreased left ventricular ejection fraction of 45% (Figure). The patient underwent pericardiostomy, and 400 mL of serosanguineous pericardial fluid was removed. Pericardial fluid cytology revealed multiple leukocytes and red blood cells without bacterial organisms. Pericardial biopsy showed chronic inflammatory changes. She was treated with intravenous methylprednisolone 100 mg daily for 3 days followed by prednisone 60 mg daily. Hydroxychloroquine was continued. Five days later, the echocardiogram showed minimal residual pericardial effusion, normal relaxation pattern, and a mild left pleural effusion. The patient continued to do well after 10 months of follow-up. She continued to take hydroxychloroquine, and prednisone was gradually tapered to 5.0 mg daily. Her MCTD remained in almost clinical remission, and the echocardiogram obtained
FIGURE. Transthoracic 2-dimensional echocardiographic imaging at initial presentation. A, The apical 4-chamber view shows a moderate pericardial effusion with right atrial collapse. B, The parasternal short-axis view demonstrates a moderate pericardial effusion. PE indicates pericardial effusion; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
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JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
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JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
Letter to the Editor
TABLE 1. Demographic Features, Clinical Manifestations, Treatment, and Clinical Outcome in MCTD With Cardiac Tamponade
Authors/Year of Publication Alpert et al2/1983
Age, y/Sex
Time from MCTD Diagnosis to Occurrence of Tamponade
Clinical Manifestations of MCTD
N/A
N/A
Pulmonary hypertension
Nunoda et al5/1986 55/Female Concomitant; symptoms Fever, Raynaud of MCTD were phenomenon, present several months polyarthralgias, before diagnosis polymyalgias Concomitant Fever, Raynaud phenomenon, Langley et al6/1994 26/Male sclerodactyly, arthritis, pleuritic chest pain, nephrotic syndrome Richard et al7/1996 22/Male
Concomitant
Fever, pleuropericarditis
Inoue et al8/1997
Concomitant
Sclerodactyly
42/Female
Autoantibodies
Cardiac Tamponade Manifestations
ANA (speckled), anti-RNP Ab
N/A
ANA (speckled), anti-RNP Ab, anti-dsDNA Ab RF ANA (speckled), anti-RNP Ab
Dyspnea, orthopnea, JVD
ANA anti-RNP Ab
Pleuritic chest pain, tachypnea, tachycardia, hypotension, pericardial rub Tachypnea, tachycardia, hypotension
Dyspnea on exertion, hypotension, altered mental status, peripheral edema, hepatomegaly, fulminant hepatic failure, renal failure Dyspnea, tachycardia, Bezerra et al9/2004 26/Female Concomitant; symptoms Weight loss, alopecia, Raynaud ANA (speckled), of MCTD were present phenomenon, sclerodactyly, anti-RNPAb, anti-Ro JVD, peripheral 6 mo before diagnosis swollen hands, polyarthritis Ab aCL Ab edema, hepatomegaly
Kumar et al10/2006 35/Female Longstanding; unknown Raynaud phenomenon, digital time period ulcers, sclerodactyly arthralgias, pleurisy, GERD
Current report/2014 58/Female 1 mo; symptoms were present for 3 mo before diagnosis
Fever, anorexia, weight loss, fatigue, hair loss, sicca symptoms, polyarthralgias, synovitis, chest pain
ANA anti-RNP Ab RF
ANA anti-RNP Ab
ANA (speckled), anti-RNP Ab, anti-Ro Ab RF
Substernal chest pain, nausea dyspnea, tachycardia, hypotension, JVD, pericardial friction rub
Fever, dyspnea on exertion, palpitations, chest pain, peripheral edema
MCTD indicates mixed connective tissue disease; N/A, not available; ANA, antinuclear antibody; anti-RNP, anti–ribonucleoprotein antibodies; TTE, transthoracic echocardiogram; RF, rheumatoid factor; JVD, jugular venous distension; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; CXR; WBC, white blood cells; LDH, lactate dehydrogenase; ECG, electrocardiogram; NSAIDs, nonsteroidal anti-inflammatory drugs; RV, right ventricle; aCL Ab, anticardiolipin antibody; GERD, gastroesophageal reflux disease; RA, right atrium.
6 months after the initial presentation showed no recurrent pericardial effusion. The most frequently reported cardiac abnormality in MCTD is pericardial disease.1–3 Pericarditis and pericardial effusion are in many instances asymptomatic or subclinical. A prospective cohort study in 38 MCTD patients examining cardiac abnormalities found that 8 (25%) of 32 patients undergoing echocardiographic evaluation had a pericardial effusion.2 Only 1 (3%) of these patients had cardiac
tamponade. A cross-sectional study in which cardiovascular examination was performed in MCTD patients disclosed similar observations; 31% of patients had pericardial effusion. The most common presenting symptom was dyspnea, occurring in 40% of patients, but 20% reported no symptoms.3 Our patient experienced mild chest discomfort without dyspnea during the initial evaluation for MCTD and subsequently developed worsening dyspnea associated with lower-extremity edema.
This prompted an echocardiographic evaluation and thus the diagnosis of cardiac tamponade. It is always challenging to distinguish MCTD from other connective tissue diseases because clinical manifestations overlap with those of SLE, scleroderma, and polymyositis/dermatomyositis. However, some diagnostic algorithms have been proposed to standardize the diagnosis of MCTD.4 The 2 most commonly used are Kahn’s and Alarcón-Segovia’s4 classification criteria.
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JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
Letter to the Editor
TABLE 1. Continued
Laboratories on Admission N/A Anemia, thrombocytopenia, ↑ESR and CRP Leukocytosis, ↑ESR, ↑LDH, nephrotic range proteinuria
N/A
Pericardial Fluid/Tissue Examination
Diagnostic Tests TTE: large pericardial effusion CXR: cardiomegaly, TTE: massive anterior and posterior pericardial effusion, swinging heart ECG: low-voltage complexes with diffuse ST-segment elevation, TTE: moderate posterior pericardial effusion TTE: unavailable results
Autopsy: diffuse inflammation N/A of periepicardial surface, fibrin deposition and neutrophils Fluid: protein 4800 mg/dL, Pericardiocentesis, glucose 107 mg/dL prednisolone 30 mg/d Fluid: few white blood cells, no Pericardiostomy, organisms, culture negative, prednisone pericardial biopsy: fibrinous 1 mg/kg per day pericarditis, neutrophilic and lymphocytic infiltrates N/A
Renal failure, ↑liver ECG: low-voltage Autopsy: fibrinous enzymes, ↑ammonia, complexes, TTE: massive pericarditis ↑ESR and CRP anterior and posterior without myocarditis pericardial effusion, swinging heart, and RV compression ↑Albumin, ↑LDH, ECG: low voltage complexes, Not performed ↑ESR and CRP, CXR: cardiomegaly, TTE: low complement massive posterior (CH100, C3, C4) pericardial effusion, swinging heart, and diastolic restriction Anemia, ↑ESR ECG: low-voltage complexes, Fluid: ANA 1:5,120, and CRP CXR: cardiomegaly, TTE: WBCs 3080/μL, 81% moderate posterior and neutrophils, total small anterior pleural protein 6.5 g/dL, glucose effusion, cardiac 73 mg/dL catheterization: equalization of diastolic pressures Anemia, ↑ESR and CRP ECG: low-voltage complexes, Cytology: multiple CXR: cardiomegaly, TTE: lymphocytes, no moderate pericardial effusion bacteria; pericardial with partial RA biopsy: mild chronic diastolic collapse inflammation
High-titer anti-U1 RNP antibodies, swollen fingers, Raynaud phenomenon, myositis/ myalgia, and synovitis are common to both classifications. Alarcón-Segovia’s criteria also include acrosclerosis. If at least 4 of these criteria are met, including high-titer anti-U1 RNP antibodies, the diagnosis of MCTD is established. On the other hand, the presence of anti-Sm and anti-dsDNA antibodies in the setting of these clinical manifestations is highly suggestive of SLE.
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Treatment
Pericardiocentesis, NSAIDs
Pericardiocentesis, prednisolone 60 mg/d
Prednisone 1 mg/kg per day, chloroquine
Pericardiocentesis, methylprednisolone 50 mg/d, then prednisone
Clinical Outcome Died
Improvement of symptoms and resolution of pericardial effusion Improvement of symptoms and resolution of pericardial effusion after one month follow-up Improvement of symptoms and resolution of pericardial effusion Died
Improvement of symptoms and resolution of pericardial effusion after 2-mo follow-up Improvement of symptoms and resolution of pericardial effusion after 6-mo follow-up
Pericardiostomy, Improvement of methylprednisolone symptoms 100 mg/d for 3 d, and resolution of then 60 mg/d prednisone, pericardial effusion hydroxychroloquine
Our patient had elevated ANAs (speckled pattern), markedly elevated anti-RNP antibodies, Raynaud phenomenon, myalgias, and synovitis in the absence of anti-Sm and anti-dsDNA antibodies. These manifestations fulfill Alarcón-Segovia’s and Kahn’s criteria for MCTD. In addition to our case, we found 7 more cases that describe cardiac tamponade in MCTD; 6 are case reports and 1 pertains to a prospective cohort study.2,5–10
Summary of reports are included in Table 1. The average age at presentation, including our case, was 38 years (range, 22–58 years). Five patients were women, 2 were men, and in 1 case the sex was unknown. In the majority of cases (5), the development of cardiac tamponade was concomitant to the diagnosis of MCTD. There was only 1 patient who had a known history of MCTD prior to cardiac tamponade. Our patient was diagnosed with MCTD 1 month before
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Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
developing cardiac tamponade. Even though the majority of patients were diagnosed with MCTD concomitantly or after developing cardiac tamponade, most patients had symptoms attributed to MCTD several months before the diagnosis was established. The most common noncardiac manifestations included polyarthralgias, sclerodactyly, and Raynaud phenomenon. Upon serological evaluation, all patients had ANAs and antiRNP antibodies in the absence of anti-Sm antibodies. Two patients, including ours, also had anti-Ro (SSA) antibodies. Other commonly reported laboratory abnormalities included anemia, elevated inflammatory markers, decreased complement levels, and 1 patient with nephrotic-range proteinuria. Dyspnea is the most common presenting manifestation of cardiac tamponade.2,3,5–10 Of the 7 cases described in the literature, 4 patients developed hemodynamic instability with hypotension and tachycardia, and 1 of these patients developed fulminant hepatic failure due to low cardiac output.6–8,10 Our patient experienced worsening dyspnea, chest pain, and lower-extremity edema; however, because of early diagnosis and rapid therapeutic intervention, she remained hemodynamically stable. Cardiac tamponade was diagnosed by echocardiography in all described cases, including the current report. Of the 5 patients who had electrocardiogram, all had low-voltage complexes, and all 4 patients with chest radiography had cardiomegaly.5,6,8–10 Only 1 patient was reported to undergo a cardiac catheterization, which disclosed elevation and equalization of diastolic pressures in all chambers.10 The echocardiographic evaluation in our patient revealed a moderate pericardial effusion with right atrial diastolic collapse. These findings together with her worsening symptoms prompted surgical intervention. Pericardial fluid has not been clearly characterized in MCTD, but findings seem to be similar to other autoimmune connective diseases affecting the pericardium, such as SLE. Previous reports have shown increased leukocyte count and elevated protein in 3 MCTD patients who had pericardial fluid analysis.5,6,10 Antinuclear antibodies were analyzed in only 1 sample, and they were found to be significantly
elevated.10 In addition, 2 autopsy examinations and 2 pericardial biopsies revealed diffuse inflammatory changes and fibrin deposition.2,6,8 These findings, especially in the presence of elevated ANA titers, are consistent with an immune-mediated inflammatory process as the pathophysiologic mechanism of pericardial effusion in MCTD. There is no criterion standard treatment for cardiac tamponade in MCTD. However, management is guided by a few reports in the literature and extrapolation from cardiac tamponade in other autoimmune connective tissue diseases. Treatment with varying doses of corticosteroids, usually with a pericardial drainage, is a common practice with evidently good response.2,5–10 Of the 8 cases described in the literature (including ours), 3 patients were managed with pericardiocentesis and corticosteroids; of these, 2 patients experienced full recovery, and 1 died after developing fulminant hepatic failure and coma.5,8,10 Two patients underwent pericardiostomy and received intravenous corticosteroids, 1 patient was treated exclusively with corticosteroids, and another responded well to nonsteroidal anti-inflammatory drugs and pericardiocentesis.6,7,9 One study reported the death of a patient; however, specific data were not provided.2 Our patient was treated successfully with a pericardiostomy and high-dose intravenous methylprednisolone followed by oral prednisone. She had no recurrent MCTD symptoms and had no pericardial effusion on follow-up echocardiogram 6 months later. In summary, patients with MCTD can develop pericardial effusion during the course of their disease. Although the majority of these effusions are small and asymptomatic, some patients may develop cardiac tamponade with hemodynamic compromise. Cardiac tamponade seems to occur early in the course of the disease. Early diagnosis is essential as therapy with corticosteroids, with or without pericardial drain, is usually effective. Thus, clinicians should consider MCTD in the differential diagnosis of a patient presenting with cardiac tamponade and symptoms suggestive of a connective tissue disease.
Letter to the Editor
Mariangelí Arroyo-Ávila, MD Luis M. Vilá, MD Division of Rheumatology Department of Medicine University of Puerto Rico Medical Sciences Campus San Juan, Puerto Rico [email protected]
REFERENCES 1. Ungprasert P, Wannarong T, Panichsillapakit T, et al. Cardiac involvement in mixed connective tissue disease: a systematic review. Int J Cardiol. 2014;171:326–330. 2. Alpert MA, Goldberg SH, Singsen BH, et al. Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation. 1983;68:1182–1193. 3. Oetgen WJ, Mutter ML, Lawless OJ, et al. Cardiac abnormalities in mixed connective tissue disease. Chest. 1983;83:185–188. 4. Alarcón-Segovia D, Cardiel MH. Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients. J Rheumatol. 1989;16:328–334. 5. Nunoda S, Mifune J, Ono S, et al. An adult case of mixed connective tissue disease associated with perimyocarditis and massive pericardial effusion. Jpn Heart J. 1986;27:129–135. 6. Langley RL, Treadwell EL. Cardiac tamponade and pericardial disorders in connective tissue diseases: case report and literature review. J Natl Med Assoc. 1994;86:149–153. 7. Richard P, Sabouret P, Vayre F, et al. Pleuropericarditis complicated of tamponade disclosing mixed connective tissue disease. Remission with non-steroidal anti-inflammatory agents. Apropos of a case [in French]. Ann Cardiol Angeiol (Paris). 1996;45:513–515. 8. Inoue T, Kamishirado H, Ishiyama E, et al. Fulminant hepatic failure due to cardiac tamponade associated with mixed connective tissue disease. J Med. 1997;28:129–135. 9. Bezerra MC, Saraiva F Jr, Carvalho JF, et al. Cardiac tamponade due to massive pericardial effusion in mixed connective tissue disease: reversal with steroid therapy. Lupus. 2004;13:618–620. 10. Kumar MS, Smith M, Pischel KD. Case report and review of cardiac tamponade in mixed connective tissue disease. Arthritis Rheum. 2006;55:826–830.
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Cardiac Tamponade in a Patient With Mixed Connective Tissue Disease To the Editor: ixed connective tissue disease (MCTD) is an autoimmune disease that presents with clinical features of systemic lupus erythematosus (SLE), scleroderma, and inflammatory muscle disease and the presence of anti–ribonucleoprotein (RNP) antibodies. It can affect a variety of organ/systems, including the heart. Pericarditis, with or without effusion, is the most common cardiac manifestation followed by mitral valve prolapse and pulmonary hypertension.1–3 However, cardiac tamponade is very unusual. Here, we describe a case of cardiac tamponade in a woman with MCTD and provide a review of other reported cases. A 59-year-old Puerto Rican woman presented with a 3-month history of tiredness, high-grade fever, anorexia, weight loss (20 lb), hair loss, oral ulcers, mild sicca symptoms, Raynaud phenomenon, arthralgias, myalgias, muscle weakness, dry cough, and chest discomfort. She had a medical history of gastroesophageal reflux disease and bronchial asthma. She was taking ibuprofen for arthralgias. She had no history of tobacco or alcohol use. Surgical history was remarkable for right carpal tunnel surgery. She had a cousin diagnosed with SLE, but the remainder of her family history was noncontributory. On physical examination, she had a body mass index of 21.9 kg/m2 with normal vital signs. She had synovitis of the
M
metacarpophalangeal joints, wrists, elbows, ankles, and metatarsophalangeal joints bilaterally. She had symmetric lower-extremity proximal muscle weakness (4/5). The remainder of the examination was unremarkable. Laboratory tests showed a white blood cell count of 6.9 109/L, hemoglobin of 11.1 g/dL and platelet count of 329 109/L. The reticulocyte count was mildly increased at 1.6%. Peripheral blood smear did not show spherocytes or schistocytes. Coombs test was negative. The Westergren erythrocyte sedimentation rate was markedly elevated at 128 mm/h as well as C-reactive protein levels at 60.8 mg/L. Serum electrolytes, renal and hepatic profiles, muscle enzymes, and coagulation tests were normal. Antinuclear antibodies (ANAs) were elevated at 1:2560 with speckled pattern. Anti–ribonucleoprotein antibodies were also markedly increased (>100 U/mL). Rheumatoid factor (14.1 U/mL) and anti-Ro antibodies (>8 U/mL) were detected. Anti-dsDNA, anti-Smith (Sm), anti–citrullinated peptide, antimyeloperoxidase, anti–proteinase 3, and anti-La antibodies were negative. A chest radiograph did not show abnormalities. Bilateral hand and wrist sonogram showed synovial hypertrophy of the metacarpophalangeal joints bilaterally. No erosions were seen. Minor salivary gland biopsy did not show inflammatory changes. Mixed connective tissue disease was diagnosed, and the patient was started on prednisone 20 mg daily and hydroxychloroquine 200 mg twice daily. One month later, she developed worsening dyspnea on exertion associated with
palpitations, chest pain, and lower-extremity swelling. She underwent outpatient echocardiography that revealed a moderate pericardial effusion with right atrial collapse. She was referred for hospitalization. Upon admission, she was afebrile with a blood pressure of 102/60 mm Hg; her heart rate was 86 beats/min, and the respiratory rate was 16 breaths/min. Examination was remarkable for lower-extremity pitting edema. There was no pericardial rub. Chest radiograph showed cardiomegaly. An electrocardiogram revealed low-voltage complexes without ST-segment changes. A repeat echocardiogram confirmed a moderate pericardial effusion with right atrial diastolic collapse, minimal mitral and aortic valve regurgitation, and a minimally decreased left ventricular ejection fraction of 45% (Figure). The patient underwent pericardiostomy, and 400 mL of serosanguineous pericardial fluid was removed. Pericardial fluid cytology revealed multiple leukocytes and red blood cells without bacterial organisms. Pericardial biopsy showed chronic inflammatory changes. She was treated with intravenous methylprednisolone 100 mg daily for 3 days followed by prednisone 60 mg daily. Hydroxychloroquine was continued. Five days later, the echocardiogram showed minimal residual pericardial effusion, normal relaxation pattern, and a mild left pleural effusion. The patient continued to do well after 10 months of follow-up. She continued to take hydroxychloroquine, and prednisone was gradually tapered to 5.0 mg daily. Her MCTD remained in almost clinical remission, and the echocardiogram obtained
FIGURE. Transthoracic 2-dimensional echocardiographic imaging at initial presentation. A, The apical 4-chamber view shows a moderate pericardial effusion with right atrial collapse. B, The parasternal short-axis view demonstrates a moderate pericardial effusion. PE indicates pericardial effusion; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
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JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
Letter to the Editor
TABLE 1. Demographic Features, Clinical Manifestations, Treatment, and Clinical Outcome in MCTD With Cardiac Tamponade
Authors/Year of Publication Alpert et al2/1983
Age, y/Sex
Time from MCTD Diagnosis to Occurrence of Tamponade
Clinical Manifestations of MCTD
N/A
N/A
Pulmonary hypertension
Nunoda et al5/1986 55/Female Concomitant; symptoms Fever, Raynaud of MCTD were phenomenon, present several months polyarthralgias, before diagnosis polymyalgias Concomitant Fever, Raynaud phenomenon, Langley et al6/1994 26/Male sclerodactyly, arthritis, pleuritic chest pain, nephrotic syndrome Richard et al7/1996 22/Male
Concomitant
Fever, pleuropericarditis
Inoue et al8/1997
Concomitant
Sclerodactyly
42/Female
Autoantibodies
Cardiac Tamponade Manifestations
ANA (speckled), anti-RNP Ab
N/A
ANA (speckled), anti-RNP Ab, anti-dsDNA Ab RF ANA (speckled), anti-RNP Ab
Dyspnea, orthopnea, JVD
ANA anti-RNP Ab
Pleuritic chest pain, tachypnea, tachycardia, hypotension, pericardial rub Tachypnea, tachycardia, hypotension
Dyspnea on exertion, hypotension, altered mental status, peripheral edema, hepatomegaly, fulminant hepatic failure, renal failure Dyspnea, tachycardia, Bezerra et al9/2004 26/Female Concomitant; symptoms Weight loss, alopecia, Raynaud ANA (speckled), of MCTD were present phenomenon, sclerodactyly, anti-RNPAb, anti-Ro JVD, peripheral 6 mo before diagnosis swollen hands, polyarthritis Ab aCL Ab edema, hepatomegaly
Kumar et al10/2006 35/Female Longstanding; unknown Raynaud phenomenon, digital time period ulcers, sclerodactyly arthralgias, pleurisy, GERD
Current report/2014 58/Female 1 mo; symptoms were present for 3 mo before diagnosis
Fever, anorexia, weight loss, fatigue, hair loss, sicca symptoms, polyarthralgias, synovitis, chest pain
ANA anti-RNP Ab RF
ANA anti-RNP Ab
ANA (speckled), anti-RNP Ab, anti-Ro Ab RF
Substernal chest pain, nausea dyspnea, tachycardia, hypotension, JVD, pericardial friction rub
Fever, dyspnea on exertion, palpitations, chest pain, peripheral edema
MCTD indicates mixed connective tissue disease; N/A, not available; ANA, antinuclear antibody; anti-RNP, anti–ribonucleoprotein antibodies; TTE, transthoracic echocardiogram; RF, rheumatoid factor; JVD, jugular venous distension; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; CXR; WBC, white blood cells; LDH, lactate dehydrogenase; ECG, electrocardiogram; NSAIDs, nonsteroidal anti-inflammatory drugs; RV, right ventricle; aCL Ab, anticardiolipin antibody; GERD, gastroesophageal reflux disease; RA, right atrium.
6 months after the initial presentation showed no recurrent pericardial effusion. The most frequently reported cardiac abnormality in MCTD is pericardial disease.1–3 Pericarditis and pericardial effusion are in many instances asymptomatic or subclinical. A prospective cohort study in 38 MCTD patients examining cardiac abnormalities found that 8 (25%) of 32 patients undergoing echocardiographic evaluation had a pericardial effusion.2 Only 1 (3%) of these patients had cardiac
tamponade. A cross-sectional study in which cardiovascular examination was performed in MCTD patients disclosed similar observations; 31% of patients had pericardial effusion. The most common presenting symptom was dyspnea, occurring in 40% of patients, but 20% reported no symptoms.3 Our patient experienced mild chest discomfort without dyspnea during the initial evaluation for MCTD and subsequently developed worsening dyspnea associated with lower-extremity edema.
This prompted an echocardiographic evaluation and thus the diagnosis of cardiac tamponade. It is always challenging to distinguish MCTD from other connective tissue diseases because clinical manifestations overlap with those of SLE, scleroderma, and polymyositis/dermatomyositis. However, some diagnostic algorithms have been proposed to standardize the diagnosis of MCTD.4 The 2 most commonly used are Kahn’s and Alarcón-Segovia’s4 classification criteria.
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www.jclinrheum.com
43
JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
Letter to the Editor
TABLE 1. Continued
Laboratories on Admission N/A Anemia, thrombocytopenia, ↑ESR and CRP Leukocytosis, ↑ESR, ↑LDH, nephrotic range proteinuria
N/A
Pericardial Fluid/Tissue Examination
Diagnostic Tests TTE: large pericardial effusion CXR: cardiomegaly, TTE: massive anterior and posterior pericardial effusion, swinging heart ECG: low-voltage complexes with diffuse ST-segment elevation, TTE: moderate posterior pericardial effusion TTE: unavailable results
Autopsy: diffuse inflammation N/A of periepicardial surface, fibrin deposition and neutrophils Fluid: protein 4800 mg/dL, Pericardiocentesis, glucose 107 mg/dL prednisolone 30 mg/d Fluid: few white blood cells, no Pericardiostomy, organisms, culture negative, prednisone pericardial biopsy: fibrinous 1 mg/kg per day pericarditis, neutrophilic and lymphocytic infiltrates N/A
Renal failure, ↑liver ECG: low-voltage Autopsy: fibrinous enzymes, ↑ammonia, complexes, TTE: massive pericarditis ↑ESR and CRP anterior and posterior without myocarditis pericardial effusion, swinging heart, and RV compression ↑Albumin, ↑LDH, ECG: low voltage complexes, Not performed ↑ESR and CRP, CXR: cardiomegaly, TTE: low complement massive posterior (CH100, C3, C4) pericardial effusion, swinging heart, and diastolic restriction Anemia, ↑ESR ECG: low-voltage complexes, Fluid: ANA 1:5,120, and CRP CXR: cardiomegaly, TTE: WBCs 3080/μL, 81% moderate posterior and neutrophils, total small anterior pleural protein 6.5 g/dL, glucose effusion, cardiac 73 mg/dL catheterization: equalization of diastolic pressures Anemia, ↑ESR and CRP ECG: low-voltage complexes, Cytology: multiple CXR: cardiomegaly, TTE: lymphocytes, no moderate pericardial effusion bacteria; pericardial with partial RA biopsy: mild chronic diastolic collapse inflammation
High-titer anti-U1 RNP antibodies, swollen fingers, Raynaud phenomenon, myositis/ myalgia, and synovitis are common to both classifications. Alarcón-Segovia’s criteria also include acrosclerosis. If at least 4 of these criteria are met, including high-titer anti-U1 RNP antibodies, the diagnosis of MCTD is established. On the other hand, the presence of anti-Sm and anti-dsDNA antibodies in the setting of these clinical manifestations is highly suggestive of SLE.
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Treatment
Pericardiocentesis, NSAIDs
Pericardiocentesis, prednisolone 60 mg/d
Prednisone 1 mg/kg per day, chloroquine
Pericardiocentesis, methylprednisolone 50 mg/d, then prednisone
Clinical Outcome Died
Improvement of symptoms and resolution of pericardial effusion Improvement of symptoms and resolution of pericardial effusion after one month follow-up Improvement of symptoms and resolution of pericardial effusion Died
Improvement of symptoms and resolution of pericardial effusion after 2-mo follow-up Improvement of symptoms and resolution of pericardial effusion after 6-mo follow-up
Pericardiostomy, Improvement of methylprednisolone symptoms 100 mg/d for 3 d, and resolution of then 60 mg/d prednisone, pericardial effusion hydroxychroloquine
Our patient had elevated ANAs (speckled pattern), markedly elevated anti-RNP antibodies, Raynaud phenomenon, myalgias, and synovitis in the absence of anti-Sm and anti-dsDNA antibodies. These manifestations fulfill Alarcón-Segovia’s and Kahn’s criteria for MCTD. In addition to our case, we found 7 more cases that describe cardiac tamponade in MCTD; 6 are case reports and 1 pertains to a prospective cohort study.2,5–10
Summary of reports are included in Table 1. The average age at presentation, including our case, was 38 years (range, 22–58 years). Five patients were women, 2 were men, and in 1 case the sex was unknown. In the majority of cases (5), the development of cardiac tamponade was concomitant to the diagnosis of MCTD. There was only 1 patient who had a known history of MCTD prior to cardiac tamponade. Our patient was diagnosed with MCTD 1 month before
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
JCR: Journal of Clinical Rheumatology • Volume 21, Number 1, January 2015
developing cardiac tamponade. Even though the majority of patients were diagnosed with MCTD concomitantly or after developing cardiac tamponade, most patients had symptoms attributed to MCTD several months before the diagnosis was established. The most common noncardiac manifestations included polyarthralgias, sclerodactyly, and Raynaud phenomenon. Upon serological evaluation, all patients had ANAs and antiRNP antibodies in the absence of anti-Sm antibodies. Two patients, including ours, also had anti-Ro (SSA) antibodies. Other commonly reported laboratory abnormalities included anemia, elevated inflammatory markers, decreased complement levels, and 1 patient with nephrotic-range proteinuria. Dyspnea is the most common presenting manifestation of cardiac tamponade.2,3,5–10 Of the 7 cases described in the literature, 4 patients developed hemodynamic instability with hypotension and tachycardia, and 1 of these patients developed fulminant hepatic failure due to low cardiac output.6–8,10 Our patient experienced worsening dyspnea, chest pain, and lower-extremity edema; however, because of early diagnosis and rapid therapeutic intervention, she remained hemodynamically stable. Cardiac tamponade was diagnosed by echocardiography in all described cases, including the current report. Of the 5 patients who had electrocardiogram, all had low-voltage complexes, and all 4 patients with chest radiography had cardiomegaly.5,6,8–10 Only 1 patient was reported to undergo a cardiac catheterization, which disclosed elevation and equalization of diastolic pressures in all chambers.10 The echocardiographic evaluation in our patient revealed a moderate pericardial effusion with right atrial diastolic collapse. These findings together with her worsening symptoms prompted surgical intervention. Pericardial fluid has not been clearly characterized in MCTD, but findings seem to be similar to other autoimmune connective diseases affecting the pericardium, such as SLE. Previous reports have shown increased leukocyte count and elevated protein in 3 MCTD patients who had pericardial fluid analysis.5,6,10 Antinuclear antibodies were analyzed in only 1 sample, and they were found to be significantly
elevated.10 In addition, 2 autopsy examinations and 2 pericardial biopsies revealed diffuse inflammatory changes and fibrin deposition.2,6,8 These findings, especially in the presence of elevated ANA titers, are consistent with an immune-mediated inflammatory process as the pathophysiologic mechanism of pericardial effusion in MCTD. There is no criterion standard treatment for cardiac tamponade in MCTD. However, management is guided by a few reports in the literature and extrapolation from cardiac tamponade in other autoimmune connective tissue diseases. Treatment with varying doses of corticosteroids, usually with a pericardial drainage, is a common practice with evidently good response.2,5–10 Of the 8 cases described in the literature (including ours), 3 patients were managed with pericardiocentesis and corticosteroids; of these, 2 patients experienced full recovery, and 1 died after developing fulminant hepatic failure and coma.5,8,10 Two patients underwent pericardiostomy and received intravenous corticosteroids, 1 patient was treated exclusively with corticosteroids, and another responded well to nonsteroidal anti-inflammatory drugs and pericardiocentesis.6,7,9 One study reported the death of a patient; however, specific data were not provided.2 Our patient was treated successfully with a pericardiostomy and high-dose intravenous methylprednisolone followed by oral prednisone. She had no recurrent MCTD symptoms and had no pericardial effusion on follow-up echocardiogram 6 months later. In summary, patients with MCTD can develop pericardial effusion during the course of their disease. Although the majority of these effusions are small and asymptomatic, some patients may develop cardiac tamponade with hemodynamic compromise. Cardiac tamponade seems to occur early in the course of the disease. Early diagnosis is essential as therapy with corticosteroids, with or without pericardial drain, is usually effective. Thus, clinicians should consider MCTD in the differential diagnosis of a patient presenting with cardiac tamponade and symptoms suggestive of a connective tissue disease.
Letter to the Editor
Mariangelí Arroyo-Ávila, MD Luis M. Vilá, MD Division of Rheumatology Department of Medicine University of Puerto Rico Medical Sciences Campus San Juan, Puerto Rico [email protected]
REFERENCES 1. Ungprasert P, Wannarong T, Panichsillapakit T, et al. Cardiac involvement in mixed connective tissue disease: a systematic review. Int J Cardiol. 2014;171:326–330. 2. Alpert MA, Goldberg SH, Singsen BH, et al. Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation. 1983;68:1182–1193. 3. Oetgen WJ, Mutter ML, Lawless OJ, et al. Cardiac abnormalities in mixed connective tissue disease. Chest. 1983;83:185–188. 4. Alarcón-Segovia D, Cardiel MH. Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients. J Rheumatol. 1989;16:328–334. 5. Nunoda S, Mifune J, Ono S, et al. An adult case of mixed connective tissue disease associated with perimyocarditis and massive pericardial effusion. Jpn Heart J. 1986;27:129–135. 6. Langley RL, Treadwell EL. Cardiac tamponade and pericardial disorders in connective tissue diseases: case report and literature review. J Natl Med Assoc. 1994;86:149–153. 7. Richard P, Sabouret P, Vayre F, et al. Pleuropericarditis complicated of tamponade disclosing mixed connective tissue disease. Remission with non-steroidal anti-inflammatory agents. Apropos of a case [in French]. Ann Cardiol Angeiol (Paris). 1996;45:513–515. 8. Inoue T, Kamishirado H, Ishiyama E, et al. Fulminant hepatic failure due to cardiac tamponade associated with mixed connective tissue disease. J Med. 1997;28:129–135. 9. Bezerra MC, Saraiva F Jr, Carvalho JF, et al. Cardiac tamponade due to massive pericardial effusion in mixed connective tissue disease: reversal with steroid therapy. Lupus. 2004;13:618–620. 10. Kumar MS, Smith M, Pischel KD. Case report and review of cardiac tamponade in mixed connective tissue disease. Arthritis Rheum. 2006;55:826–830.
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