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Pericardial disease in rheumatoid arthritis
Pericqrdial Disease in Pheumatoid Arthritis
J. THOMAS JOHN, Jr., M.D. AUBREY HOUCH. M.D. JOHN S. SERGENT, M.D. Nushvillr. ‘l’ttnnessec
Six patients with rheumatoid constrictive pericarditis, five seen in q two and one half year period, are described. All patients were male, all had rheumgtoid factor, and all had active arthritis. Diagnosis was suspected from careful physical examination and confirmed in five patients by cardiac catheterization. Perjcardiectomy was successful in all five patients on whom it was performed. Rheumatoid constrictive pericarditis should be suspected in any patient with rheumatoid arthritis and unexplained signs of right heart failure. Although pericarditis is noted on postmortem examination in as many as 50 per cent of patients with rheumatoid arthritis [I-J], clinicaliy important pcricardial disease isseen much less frequently [5,6].Several recent articles have discussed the clinical and pathologic features of patients with this disease (7-91, and Thadani, Iveson and Wright [lo] have pointed out that the disease may be more common than is generally appreciated and that it has veiy serious implications. At the Vanderbilt University Medical Center and the Nashville Veterans Administration Hospital WC have seen five patients with rheumatoid constrictive pericarditis or tamponade within a two and one half year period, all of whom were successfully treated surgically. These patients, plus an additional one from the recent autopsy files, arc the subject of this report. REPRESENTATIVE CASE REPORTS Case 1. This 58 year old Caucasian man cvaluatinn
of arthritis
was
first seen on januar)~ 26, 1976. for
and progressive refractory
lower extremity
&ma.
Rheumatoid arthritis had dovclopc:d 20 years earlier. He had received a short term of gold salt therapy early in the course. but in recent years therapy had consisted of anti-inflammatory
agents and prcdnisone,
following the patient’s second total hip rcplacemcnt rienced progressive edema of the lower extremities.
8 mg daily. Shortly
in AU~IIS! 1975, he expeHe denied orthopnea,
nocturnal dvspnea and chest pain. Examination
revealed
a
blood pressure of lO8/89
From the Departments of Medicine and Pathol-
paradoxic pulse. The pulse rate
ogy, Vanderbilt Universitv School of Mcdicinc; and the Veterans Administration Hospital, Nashville, Tennessee. This study was supported by a grant from the Regional Medical Program. and by grants frqm the Medical Rcscarch Scrviw
tention was marked, and increased with inspiration
of the Veterans Administration Hospitals. Rcquests for reprints should bo addrcsscd to Dr. John S. Sergept, Department of Mcdicinc. Vanderbilt University School of Modicinc. Nashville. Tennessee. Manuscript accepted October 23. 1978.
lungs wcrn clear to auscultation.
was
80/min
mm Hg with an 6 mm
and regular. Jugular venous dis(I
1{cart sounds were muffled. There was a grade
2/6 early systolic murmur with no gallop or rub. The liver was not palpable. There was no ascites. but tense pitting peripheral edema was present below the knees. Widespread scvcrc changes of chronic rheumatoid arthritis were present. most marked in the hands, feet and shoulders. The patient was anemic. with a hematocrit va!ue of 33 per cent. and a Iatcx fixation test for rheumatoid
factor
was
positive at a titer of 1:2560. Otherwise.
laboratory data on admission were unremarkable. An electrocardiogram show& loft atrial enlargement with nonspecific ST-T wwe changes. The in-
March 1979
The American Journal of Medicine
Volume 86
365
PERICARDIAL DISEASE IN RHEUMATOID
ARTHRITIS-JOHN
termediate purified protein derivative skin test was negative. A chest film showed small bilateral pleural effusions, basilar honey-combed interstitial markings and borderline cardiac enlargement. Echocardiogram suggested a small pericardial effusion. Cardiac catheterization showed essentially equal diastolic pressure in ali chambers, compatible with constrictive pericarditis. On February 23, the patient underwent removal of a densely adherent pericardium, which revealed typical rheumatoid granulomas microscopically [Figure 1). Following surgery, mild congestive heart failure developed for which the patient required therapy with digitalis and diuretics. but this gradually resolved and he is now free of any cardiac symptoms.
Comment: In this 58 year old white man right heart failure developed after 20 years of severe, noduleforming rheumatoid arthritis. Cardiac catheterization
ET AL.
confirmed constrictive pericarditis; following surgery, left heart failure developed which gradually cleared. Case 2. This 51 year old white man was admitted to the hos-
pital on April 22,1976. because of chest pain. He had severe seropositive rheumatoid arthritis of 18 years’ duration for which he had been treated with nonsteroidal anti-inflammatory agents and intermittent intra-articular steroids. Ten months prior to admission, an asymptomatic pericardial friction rub was heard. Three months prior to admission, he experienced intermittent sharp, stabbing precordial chest pain accentuated by lying in the prone position, a 10 pound weight loss, night sweats and a nonproductive cough. On physical examination, blood pressure was 120/75 mm Hg and the pulse rate was 90/min with a 15 mm paradox. He was afebrile. Jugular venous distention was present 3 cm above the clavicle at 45 degrees, but venous distentiori decreased
F@ure 2.
Case 2. Pericarditis suggestive of rheumatoid etiology in a patient with long-standing rheumatoid arthritis. A, pkardial surface demonstiating areas of fibiinoid necrosis (f) and of mononuclear cells arranged in a pseudopalisade (p). Dense inflammation and proliferating capillaries are also present. Hematoxylin and eosin stain; magnification X 20. B, area of necrosis (n) and granulation tissue (g) bordered by fibrosis (f). Hematoxylin and eosin stain; magnification X 320, reduced by 37 per cent.
386
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PERICARDIAL DISEASE IN RHEUMATOID
slightly with inspiration. The lungs were clear to auscultation. There was a three component, high-pitched, scratchy friction rub heard best with the patient in the sitting position. There was a soft atria1 gallop. The liver was palpable 4 cm below the right costal margin. There was no peripheral edema. The patient had multiple rheumatoid nodules over the extensor surfaces of his forearms and typical advanced rheumatoid arthritis involving most joints, especially shoulders, elbows, hands and feet. Chest film revealed a normal-sized but slightly globular shaped heart. The lungs were clear without pleural effusion. An electrocardiogram revealed nonspecific ST-T wave changes. The hematocrit value was 45 per cent and the white blood cell count $1Wmm3 with a nornial differential. The latex fixation test for rheumatoid factor was positive at a titer antibody test was negative. An of 1:1280. The antinuclear echocardiogram suggested a small pericardial effusion. The intermediate purified protein derivative skin test was positive. Isoniazid therapy was begun, but symptoms worsened over the next three weeks. A positive Kussmaul’s sign had developed as well as increased hepatomegaly and low voltage on the electrocardiogram. Cardiac catheterization revealed classic signs of pericardial constriction. On June 8 pericardiectomy was performed with removal of thick, densely adherent pericardium; a dramatic and immediate increase in the right ventricular size followed. Pathologic examination revealed chronic nonspecific inflammation with several small granulomatous foci resembling rheumatoid nodules (Figure 2). Careful search for tubercle bacilli and other organisms was negative. The patient tolerated the procedure well and is currently asymptomatic from his cardiovascular disease.
Comment: In this 51 year old white man constrictive pericarditis developed after 18 years of disease. Response to pericardiectomy was immediate. and he has had no further cardiovascular symptoms. Case 3. This Gl year old Caucasian
man had the onset of rheumatoid arthritis in 1970 Icading to complete disability by November 1971. Except for a four to six week course of oral corticosteroicls in 1972, treatment was limited to salicylates. In the spring of 1974 pedal cdcma. clyspnca on exertion and nonhealing lllcers on the lower extremities developed. In June 1975. the patient was admitted to the Nashville Veterans Administration Hospital. Physical examination revealed a wasted man with scvcrc edema and ascites. His pulse rate was 12Umin and irregular, and the blood pressure was 110/70 mm Hg with a paradoxic pulse of 12 to 15 mm Hg. The jugular veins were prominently distended at 45 degrees, with accentuation during inspiration (Kussmaul’s sign.) Cardiac examination revealed a grade 2/6 systolic murmur along the lower left sternal border. Ventricular and atrial gallops were audible. The liver was palpable 10 cm below the right costal margin, the spleen tip was palpable, and ascites was prominent. Examination of the cxtremities revealed severe changes of rheumatoid arthritis with deformities of the hands, elbows. shoulders, hips and knees. Prominent edema was present, and several subcutaneous
ARTHRITIS-JOHN
ET AL.
Figure 3. Case 5. Peripheral ischemic ulcers in a patient with severe rheumatoid arthritis and concomitant vasculitis and constrictive pericarditis.
nodules were present along the extensor surfaces of both forearms. A number of well circumscribed 1 to 3 cm ulcerations were present on the lower legs bilaterally (Figure 3). Electrocardiogram revealed atrial flutter with a 2:l block. with right axis dcvintion and nonspecific S-T and T wave changes. A chest film showed a slightly enlarged globular heart with small bilateral pleural cffusions and basilar pulmonary fibrosis. An cchocardiogram revealccl small pleural and pcricardial cffusions. The hematocrit value was 39 per cent and the crythrocyte sedimentation rate 43 mm/hour (Wintrobe). Otherwise the routine laboratory work was unrcmarkable. The latex fixation test for rheumatoid factor was ppsitivc at a titer of 1:25FO. Cryoglobulins were dctccted and found to consist of polyclonal immunoglobulins C (IgC) and M (IBM). Antinuclear antibody was not present. Total hcmolytic complement and the third component of complement (C3) were normal. Skin biopsy showed vasculitis involving small vessels. The tuberculin skin test was negative. Cardiac catheterization revcalcd cyual diastolic pressures in all cardiac chambers. Pcricardioccntcsis was pcrformecl with removal of 240 cc of bloody fluid with a hematocrit value of 9 per cent. Repeat catheterization following a second pcri-
March 1979
The American Journal of Medicine
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367
PERICARDIAL DISEASE IN RHEUMATOID
ARTHRITIS--jOHN
Figure 4. Case 3. Nonspecificpericarditis in d datient with severe rheumatoid arthritis. Scattered inflamqatory cells permeate the thickened, fibrotic pericardium. No necrosis is preient. Hematoxylin and eosin stain; magnificati6n X 200, rhduced by 57 per cent.
cardibcentesis of 180 cc fluid revealed no change in pressures. On September 191975, pericardiectomy was performed with removal of a very thick, adherent pericardium. Examination revealed chronic inflammation and fibrosis (Figure 4) without evidence of acid-fast bacilli or other infectious agents. There was rapid postoperative clearing of the heart failure, and the patient has had no recurrent cardiovascular asymbtoms. His aortic diastolic murmur persists. Comment: In this 61 year old white man with seropositive, nodule-forming rheumatoid arthritis, constrictive pericarditis developed after five years of illness. Despite change of vasculitis, aortic insufficiency and severe debilita Pion, this patient had an excellent response to pericardiectomy and is now doing well. COMMEWS
All of our patients were white men, ranging in age from 41 to 63 years. All met criteria for classic rheumatoid arthritis, all were seropositive, and all had rheumatoid nodules (Table I). The duration of rheumatoid arthritis prior to the onset of symptoms averaged 12 years. In one patient (Case 5) the rheumatoid arthritis presented with TABLE I
Caee No.
308
ET AL
simultaneous onset of articular and pericardial manifestations. tione of our patients had antinuclear antibodies or Sjogren’s syndrome. Four patients with long-standing rheumatoid art,hritis also had pulmonary manifestations of rheumatoid arthritis with bibasilar fibrosis, and five patients had pleural effusions: In &-iceof these, pericardiocentesis was performed: the fluidhad 92,000 white cells/mm3 with 85 per cent polymorphonuclear leukocytesand a glucose level of TOmg/dl. CJne patient (Case 31, in addition to pulmonary fibrosis, had active rheumatoid vasculitis on presentation. All patients had active rheumatoid arthritis at the time of presentation. Presenting Sympibk Two patterns were evident in the presenting symptoms of our ,six patients. Four patients had a very chronic and insidious illness with a duration of symptoms averaging 12 months (4.5 to 44 months] prior to diagnosis (Table II). All of these patients presented with t,he chief complaint of peripheral edema, and all four had significant congestive heart failure. In two of these patients, abdominal distention from ascitic fluid was also a presenting symptom. In none of these four patients was there a history of chest pain. The other two patients (Cases 2 and 5) had a much shorter duration of symptoms and had, as their presenting symptoms, chest pain, fever and night sweats, Peripheral edema was absent in these two patients. All six of our patients presented with some degree of dyspnea. Physical Findings at Presknfation. All six patients had a blood pressure suggestive, of, or at least compatible with, poricardial constriction. Average blood pressure was 106/76 mm Hg, tiith a range of 75/60 to 124/80 mm Hg. Increased jugular venous pressure tias present in five of the six. Marked obesity may have obscured its presence in the, other patient. Paradoxic pulse was present in four of the patients, and Kdssmaul’s sign was noted in three. A less common physical finding in our experience was pericardial friction rub. This occurred very transiently in one patient [Case 1)and was a persistent finding in only one of the the six cases. Peripheral edema, as mentioned, was a prominent
Summary of Cases Duration 01 Rbeumaloid Arthrltls
1 2 3
20 yr 18yr
4 5 6
12yr 2mo 15 yr
5 yr
Latex Fixation Titer
Subcutaneous Nodules
1:2560 1:1280 1:2560
+ + +
1:64b 1:20 Not done: slide test positive
+ +
March 197!1 The American Journal of Medicine
+
Volume 66
ANA -
Sjogren’s Syndrome -
-
Other Extra-Articular Manitestalions Pulinonary fibrosis None Vasculitis, pulmonary fibrosis, ? cardiac involvement Pulmonary fibrosis None
Pulmonary
fibrosis
PERICARDIAL DISEASE IN RHEUMATOID
TABLE II
ARTHRITIS-JOHN
ET AL.
Presenting Symptoms
Case No.
Duration of Cardiac Symptoms
Dyspnea
Edema
1 2
4112 mo 4mo
+ +
+ -
-
+ + + +
+ +
+
+
+
3 4 5 6
5mo 38 mo 2 mo 24 mo
finding in the four patients with long-standing symptoms; in three of these, ascites was also present. No edema or ascites was present in the two patients with more acute presentations. Hepatomegaly was present in five of the six patients. Laboratory Data. Electrocardiogram was not helpful. The predominant finding was nonspecific S-T and T wave changes. In only one patient (Case 5) was there a strong suggestion of pericardial tamponade. Borderline low voltage was present in one other patient. On chest film pleural effusion was present in five of the six patients and was bilateral in the four patients with chronic presentations, all of whom also had basilar interstitial fibrosis. Massive cardiac enlargement was present in two patients and corresponded to the presence of large pericardial effusions. Echocardiogram was performed in four cases and was not suggestive of constriction or tamponade in any. The definitive test in our experience was cardiac catheterization, which was diagnostic in all five instances in which it was performed. Only one patient did not undergo catheterization (Case 6); in this patient, the diagnosis of rheumatoid constrictve pericarditis with tamponade was made only at postmortem examination. The other five patients underwent pericardial resection with excellent results. Two had postoperative cardiomegaly and increased congestive failure, but this was transient, and all five patients currently have no cardiac symptoms. The pathology of the resected pericardium varied from nonspecific fibrinous changes (three patients] to changes strongly suggestive of rheumatoid arthritis [two patients) including one patient whose pericardium showed rheumatoid-like nodules. The one patient who came to autopsy demonstrated pericardial tamponade with a nonspecific chronic fibrinous pericarditis.
Abdominal Distention
Chest Pain
Fever
+
+
+
+
medical center suggests that the entity may occur with greater frequency than is commonly appreciated. As was demonstrated in Case 6, many other diagnostic considerations have to be taken into account in these patients, including amyloidosis, malignancy, recurrent pulmonary emboli, and the like. In addition, with the chronicity of many of the symptoms, the diagnosis of congestive heart failure secondary to coronary artery disease was often the initial diagnosis. Since the only common denominators in these patients were rheumatoid arthritis and right heart failure, we strongly believe that this combination of symptoms should always alert the clinician to the possibility of rheumatoid constrictive pericarditis and/or pericardial tainponade. The diagnostic tools most helpful in this setting were found to be careful physical examination; cardiac catheterization was diagnostic in all cases studied. Several aspects of our patient population deserve comment. All were white men and all had active rheumatoid arthritis with subcutaneous nodules at the time of presentation. Four of our patients also had interstitial pulmonary fibrosis, a complication also seen predominantly in men in whom rheumatoid nodules form [ll]. Our experience with this disease supports the impression of Thadani, Iveson and Wright [lo] that the only effective treatment of rheumatoid constrictive pericarditis is surgical pericardiectomy. All five of our patients so treated are currently asymptomatic with regard to their cardiovascular status. We conclude that rheumatoid constrictive pericardial disease is more common than is generally appreciated, Indeed, our only fatal case was rather obvious in retrospect, but the diagnosis was never considered prior to death. Since constrictive pericarditis is probably fatal if untreated, and since excellent therapy is available, we recommend that all patients with rheumatoid arthritis in whom right heart failure develops should be
COMMENTS The demonstration of five cases of serious rheumatoid pericarditis over a two and a half year period in this
considered to have pericardial disease until this diagnosis is excluded
by appropriate
studies.
REFERENCES 1.
Bonfigilio T. Atwntcr E: He;lrt tliscasc
in I)oticnts with scropositive rheumatoid arthritis: a controllctl strdy ar,tl rcview. Arch Intern Mctl 124: 714. 1969.
2.
3.
March 1979
Bywatcrs EGL: ‘l’hc rclalion Ixlwccn heart and joint tiiscase. Br Hcilrt J 12: 101, 1950. Cluickshank B: Heart lesions in rheumatoid disease. J P;lthol
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Volume 66
369
PERICARDIAL DISEASE IN RHEUMATOID ARTHRITIS-JOHN
4.
Bact 76: 223,1958. Lebowitz WB: The heart in rheumatoid arthritis, A clinical and pathological study of 62 cases. Ann Intern Med 58: 102. 1963.
5.
Kirk J, Cosh J: The pericarditis of rheumatoid arthritis. J Med 38: 397, 1969. 6. Golding JR: Rheumatoid pericarditis. Br Med J 1: 919, 1963 7. Reimer KA, Rodgers RF, Oyasu R: Rheumatoid arthritis with rheumatoid heart disease and granulomatous aortitis. JAMA 235: 2510.1976. 8. Franc0 AE, Levine HD, Hall AP: Rheumatoid pericarditis.
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March 1979
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ET AL.
Report of 17 cases diagnosed clinically. Ann Intern Med 77: 837. 1972. 9. Siegmeth W, Eberl R: Gelenksferne Manifestationen Der chronischen Polyarthritis. Wien Klin Wochenschrift 88: 81. 1976. 10. Thadani U, Iveson JMI, Wright V: Cardiac tamponade, constrictive pericarditis and pericardial resection in rheumatoid arthritis. Medicine (Baltimore] 54: 261,1975. 11. Walker WC, Wright V: Diffuse interstitial pulmonary fibrosis and rheumatoid arthritis. Ann Rheum Dis 28: 252, 1969.
Volume 66
J. THOMAS JOHN, Jr., M.D. AUBREY HOUCH. M.D. JOHN S. SERGENT, M.D. Nushvillr. ‘l’ttnnessec
Six patients with rheumatoid constrictive pericarditis, five seen in q two and one half year period, are described. All patients were male, all had rheumgtoid factor, and all had active arthritis. Diagnosis was suspected from careful physical examination and confirmed in five patients by cardiac catheterization. Perjcardiectomy was successful in all five patients on whom it was performed. Rheumatoid constrictive pericarditis should be suspected in any patient with rheumatoid arthritis and unexplained signs of right heart failure. Although pericarditis is noted on postmortem examination in as many as 50 per cent of patients with rheumatoid arthritis [I-J], clinicaliy important pcricardial disease isseen much less frequently [5,6].Several recent articles have discussed the clinical and pathologic features of patients with this disease (7-91, and Thadani, Iveson and Wright [lo] have pointed out that the disease may be more common than is generally appreciated and that it has veiy serious implications. At the Vanderbilt University Medical Center and the Nashville Veterans Administration Hospital WC have seen five patients with rheumatoid constrictive pericarditis or tamponade within a two and one half year period, all of whom were successfully treated surgically. These patients, plus an additional one from the recent autopsy files, arc the subject of this report. REPRESENTATIVE CASE REPORTS Case 1. This 58 year old Caucasian man cvaluatinn
of arthritis
was
first seen on januar)~ 26, 1976. for
and progressive refractory
lower extremity
&ma.
Rheumatoid arthritis had dovclopc:d 20 years earlier. He had received a short term of gold salt therapy early in the course. but in recent years therapy had consisted of anti-inflammatory
agents and prcdnisone,
following the patient’s second total hip rcplacemcnt rienced progressive edema of the lower extremities.
8 mg daily. Shortly
in AU~IIS! 1975, he expeHe denied orthopnea,
nocturnal dvspnea and chest pain. Examination
revealed
a
blood pressure of lO8/89
From the Departments of Medicine and Pathol-
paradoxic pulse. The pulse rate
ogy, Vanderbilt Universitv School of Mcdicinc; and the Veterans Administration Hospital, Nashville, Tennessee. This study was supported by a grant from the Regional Medical Program. and by grants frqm the Medical Rcscarch Scrviw
tention was marked, and increased with inspiration
of the Veterans Administration Hospitals. Rcquests for reprints should bo addrcsscd to Dr. John S. Sergept, Department of Mcdicinc. Vanderbilt University School of Modicinc. Nashville. Tennessee. Manuscript accepted October 23. 1978.
lungs wcrn clear to auscultation.
was
80/min
mm Hg with an 6 mm
and regular. Jugular venous dis(I
1{cart sounds were muffled. There was a grade
2/6 early systolic murmur with no gallop or rub. The liver was not palpable. There was no ascites. but tense pitting peripheral edema was present below the knees. Widespread scvcrc changes of chronic rheumatoid arthritis were present. most marked in the hands, feet and shoulders. The patient was anemic. with a hematocrit va!ue of 33 per cent. and a Iatcx fixation test for rheumatoid
factor
was
positive at a titer of 1:2560. Otherwise.
laboratory data on admission were unremarkable. An electrocardiogram show& loft atrial enlargement with nonspecific ST-T wwe changes. The in-
March 1979
The American Journal of Medicine
Volume 86
365
PERICARDIAL DISEASE IN RHEUMATOID
ARTHRITIS-JOHN
termediate purified protein derivative skin test was negative. A chest film showed small bilateral pleural effusions, basilar honey-combed interstitial markings and borderline cardiac enlargement. Echocardiogram suggested a small pericardial effusion. Cardiac catheterization showed essentially equal diastolic pressure in ali chambers, compatible with constrictive pericarditis. On February 23, the patient underwent removal of a densely adherent pericardium, which revealed typical rheumatoid granulomas microscopically [Figure 1). Following surgery, mild congestive heart failure developed for which the patient required therapy with digitalis and diuretics. but this gradually resolved and he is now free of any cardiac symptoms.
Comment: In this 58 year old white man right heart failure developed after 20 years of severe, noduleforming rheumatoid arthritis. Cardiac catheterization
ET AL.
confirmed constrictive pericarditis; following surgery, left heart failure developed which gradually cleared. Case 2. This 51 year old white man was admitted to the hos-
pital on April 22,1976. because of chest pain. He had severe seropositive rheumatoid arthritis of 18 years’ duration for which he had been treated with nonsteroidal anti-inflammatory agents and intermittent intra-articular steroids. Ten months prior to admission, an asymptomatic pericardial friction rub was heard. Three months prior to admission, he experienced intermittent sharp, stabbing precordial chest pain accentuated by lying in the prone position, a 10 pound weight loss, night sweats and a nonproductive cough. On physical examination, blood pressure was 120/75 mm Hg and the pulse rate was 90/min with a 15 mm paradox. He was afebrile. Jugular venous distention was present 3 cm above the clavicle at 45 degrees, but venous distentiori decreased
F@ure 2.
Case 2. Pericarditis suggestive of rheumatoid etiology in a patient with long-standing rheumatoid arthritis. A, pkardial surface demonstiating areas of fibiinoid necrosis (f) and of mononuclear cells arranged in a pseudopalisade (p). Dense inflammation and proliferating capillaries are also present. Hematoxylin and eosin stain; magnification X 20. B, area of necrosis (n) and granulation tissue (g) bordered by fibrosis (f). Hematoxylin and eosin stain; magnification X 320, reduced by 37 per cent.
386
March 1979
The American Journal of Medicine
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PERICARDIAL DISEASE IN RHEUMATOID
slightly with inspiration. The lungs were clear to auscultation. There was a three component, high-pitched, scratchy friction rub heard best with the patient in the sitting position. There was a soft atria1 gallop. The liver was palpable 4 cm below the right costal margin. There was no peripheral edema. The patient had multiple rheumatoid nodules over the extensor surfaces of his forearms and typical advanced rheumatoid arthritis involving most joints, especially shoulders, elbows, hands and feet. Chest film revealed a normal-sized but slightly globular shaped heart. The lungs were clear without pleural effusion. An electrocardiogram revealed nonspecific ST-T wave changes. The hematocrit value was 45 per cent and the white blood cell count $1Wmm3 with a nornial differential. The latex fixation test for rheumatoid factor was positive at a titer antibody test was negative. An of 1:1280. The antinuclear echocardiogram suggested a small pericardial effusion. The intermediate purified protein derivative skin test was positive. Isoniazid therapy was begun, but symptoms worsened over the next three weeks. A positive Kussmaul’s sign had developed as well as increased hepatomegaly and low voltage on the electrocardiogram. Cardiac catheterization revealed classic signs of pericardial constriction. On June 8 pericardiectomy was performed with removal of thick, densely adherent pericardium; a dramatic and immediate increase in the right ventricular size followed. Pathologic examination revealed chronic nonspecific inflammation with several small granulomatous foci resembling rheumatoid nodules (Figure 2). Careful search for tubercle bacilli and other organisms was negative. The patient tolerated the procedure well and is currently asymptomatic from his cardiovascular disease.
Comment: In this 51 year old white man constrictive pericarditis developed after 18 years of disease. Response to pericardiectomy was immediate. and he has had no further cardiovascular symptoms. Case 3. This Gl year old Caucasian
man had the onset of rheumatoid arthritis in 1970 Icading to complete disability by November 1971. Except for a four to six week course of oral corticosteroicls in 1972, treatment was limited to salicylates. In the spring of 1974 pedal cdcma. clyspnca on exertion and nonhealing lllcers on the lower extremities developed. In June 1975. the patient was admitted to the Nashville Veterans Administration Hospital. Physical examination revealed a wasted man with scvcrc edema and ascites. His pulse rate was 12Umin and irregular, and the blood pressure was 110/70 mm Hg with a paradoxic pulse of 12 to 15 mm Hg. The jugular veins were prominently distended at 45 degrees, with accentuation during inspiration (Kussmaul’s sign.) Cardiac examination revealed a grade 2/6 systolic murmur along the lower left sternal border. Ventricular and atrial gallops were audible. The liver was palpable 10 cm below the right costal margin, the spleen tip was palpable, and ascites was prominent. Examination of the cxtremities revealed severe changes of rheumatoid arthritis with deformities of the hands, elbows. shoulders, hips and knees. Prominent edema was present, and several subcutaneous
ARTHRITIS-JOHN
ET AL.
Figure 3. Case 5. Peripheral ischemic ulcers in a patient with severe rheumatoid arthritis and concomitant vasculitis and constrictive pericarditis.
nodules were present along the extensor surfaces of both forearms. A number of well circumscribed 1 to 3 cm ulcerations were present on the lower legs bilaterally (Figure 3). Electrocardiogram revealed atrial flutter with a 2:l block. with right axis dcvintion and nonspecific S-T and T wave changes. A chest film showed a slightly enlarged globular heart with small bilateral pleural cffusions and basilar pulmonary fibrosis. An cchocardiogram revealccl small pleural and pcricardial cffusions. The hematocrit value was 39 per cent and the crythrocyte sedimentation rate 43 mm/hour (Wintrobe). Otherwise the routine laboratory work was unrcmarkable. The latex fixation test for rheumatoid factor was ppsitivc at a titer of 1:25FO. Cryoglobulins were dctccted and found to consist of polyclonal immunoglobulins C (IgC) and M (IBM). Antinuclear antibody was not present. Total hcmolytic complement and the third component of complement (C3) were normal. Skin biopsy showed vasculitis involving small vessels. The tuberculin skin test was negative. Cardiac catheterization revcalcd cyual diastolic pressures in all cardiac chambers. Pcricardioccntcsis was pcrformecl with removal of 240 cc of bloody fluid with a hematocrit value of 9 per cent. Repeat catheterization following a second pcri-
March 1979
The American Journal of Medicine
Volume 66
367
PERICARDIAL DISEASE IN RHEUMATOID
ARTHRITIS--jOHN
Figure 4. Case 3. Nonspecificpericarditis in d datient with severe rheumatoid arthritis. Scattered inflamqatory cells permeate the thickened, fibrotic pericardium. No necrosis is preient. Hematoxylin and eosin stain; magnificati6n X 200, rhduced by 57 per cent.
cardibcentesis of 180 cc fluid revealed no change in pressures. On September 191975, pericardiectomy was performed with removal of a very thick, adherent pericardium. Examination revealed chronic inflammation and fibrosis (Figure 4) without evidence of acid-fast bacilli or other infectious agents. There was rapid postoperative clearing of the heart failure, and the patient has had no recurrent cardiovascular asymbtoms. His aortic diastolic murmur persists. Comment: In this 61 year old white man with seropositive, nodule-forming rheumatoid arthritis, constrictive pericarditis developed after five years of illness. Despite change of vasculitis, aortic insufficiency and severe debilita Pion, this patient had an excellent response to pericardiectomy and is now doing well. COMMEWS
All of our patients were white men, ranging in age from 41 to 63 years. All met criteria for classic rheumatoid arthritis, all were seropositive, and all had rheumatoid nodules (Table I). The duration of rheumatoid arthritis prior to the onset of symptoms averaged 12 years. In one patient (Case 5) the rheumatoid arthritis presented with TABLE I
Caee No.
308
ET AL
simultaneous onset of articular and pericardial manifestations. tione of our patients had antinuclear antibodies or Sjogren’s syndrome. Four patients with long-standing rheumatoid art,hritis also had pulmonary manifestations of rheumatoid arthritis with bibasilar fibrosis, and five patients had pleural effusions: In &-iceof these, pericardiocentesis was performed: the fluidhad 92,000 white cells/mm3 with 85 per cent polymorphonuclear leukocytesand a glucose level of TOmg/dl. CJne patient (Case 31, in addition to pulmonary fibrosis, had active rheumatoid vasculitis on presentation. All patients had active rheumatoid arthritis at the time of presentation. Presenting Sympibk Two patterns were evident in the presenting symptoms of our ,six patients. Four patients had a very chronic and insidious illness with a duration of symptoms averaging 12 months (4.5 to 44 months] prior to diagnosis (Table II). All of these patients presented with t,he chief complaint of peripheral edema, and all four had significant congestive heart failure. In two of these patients, abdominal distention from ascitic fluid was also a presenting symptom. In none of these four patients was there a history of chest pain. The other two patients (Cases 2 and 5) had a much shorter duration of symptoms and had, as their presenting symptoms, chest pain, fever and night sweats, Peripheral edema was absent in these two patients. All six of our patients presented with some degree of dyspnea. Physical Findings at Presknfation. All six patients had a blood pressure suggestive, of, or at least compatible with, poricardial constriction. Average blood pressure was 106/76 mm Hg, tiith a range of 75/60 to 124/80 mm Hg. Increased jugular venous pressure tias present in five of the six. Marked obesity may have obscured its presence in the, other patient. Paradoxic pulse was present in four of the patients, and Kdssmaul’s sign was noted in three. A less common physical finding in our experience was pericardial friction rub. This occurred very transiently in one patient [Case 1)and was a persistent finding in only one of the the six cases. Peripheral edema, as mentioned, was a prominent
Summary of Cases Duration 01 Rbeumaloid Arthrltls
1 2 3
20 yr 18yr
4 5 6
12yr 2mo 15 yr
5 yr
Latex Fixation Titer
Subcutaneous Nodules
1:2560 1:1280 1:2560
+ + +
1:64b 1:20 Not done: slide test positive
+ +
March 197!1 The American Journal of Medicine
+
Volume 66
ANA -
Sjogren’s Syndrome -
-
Other Extra-Articular Manitestalions Pulinonary fibrosis None Vasculitis, pulmonary fibrosis, ? cardiac involvement Pulmonary fibrosis None
Pulmonary
fibrosis
PERICARDIAL DISEASE IN RHEUMATOID
TABLE II
ARTHRITIS-JOHN
ET AL.
Presenting Symptoms
Case No.
Duration of Cardiac Symptoms
Dyspnea
Edema
1 2
4112 mo 4mo
+ +
+ -
-
+ + + +
+ +
+
+
+
3 4 5 6
5mo 38 mo 2 mo 24 mo
finding in the four patients with long-standing symptoms; in three of these, ascites was also present. No edema or ascites was present in the two patients with more acute presentations. Hepatomegaly was present in five of the six patients. Laboratory Data. Electrocardiogram was not helpful. The predominant finding was nonspecific S-T and T wave changes. In only one patient (Case 5) was there a strong suggestion of pericardial tamponade. Borderline low voltage was present in one other patient. On chest film pleural effusion was present in five of the six patients and was bilateral in the four patients with chronic presentations, all of whom also had basilar interstitial fibrosis. Massive cardiac enlargement was present in two patients and corresponded to the presence of large pericardial effusions. Echocardiogram was performed in four cases and was not suggestive of constriction or tamponade in any. The definitive test in our experience was cardiac catheterization, which was diagnostic in all five instances in which it was performed. Only one patient did not undergo catheterization (Case 6); in this patient, the diagnosis of rheumatoid constrictve pericarditis with tamponade was made only at postmortem examination. The other five patients underwent pericardial resection with excellent results. Two had postoperative cardiomegaly and increased congestive failure, but this was transient, and all five patients currently have no cardiac symptoms. The pathology of the resected pericardium varied from nonspecific fibrinous changes (three patients] to changes strongly suggestive of rheumatoid arthritis [two patients) including one patient whose pericardium showed rheumatoid-like nodules. The one patient who came to autopsy demonstrated pericardial tamponade with a nonspecific chronic fibrinous pericarditis.
Abdominal Distention
Chest Pain
Fever
+
+
+
+
medical center suggests that the entity may occur with greater frequency than is commonly appreciated. As was demonstrated in Case 6, many other diagnostic considerations have to be taken into account in these patients, including amyloidosis, malignancy, recurrent pulmonary emboli, and the like. In addition, with the chronicity of many of the symptoms, the diagnosis of congestive heart failure secondary to coronary artery disease was often the initial diagnosis. Since the only common denominators in these patients were rheumatoid arthritis and right heart failure, we strongly believe that this combination of symptoms should always alert the clinician to the possibility of rheumatoid constrictive pericarditis and/or pericardial tainponade. The diagnostic tools most helpful in this setting were found to be careful physical examination; cardiac catheterization was diagnostic in all cases studied. Several aspects of our patient population deserve comment. All were white men and all had active rheumatoid arthritis with subcutaneous nodules at the time of presentation. Four of our patients also had interstitial pulmonary fibrosis, a complication also seen predominantly in men in whom rheumatoid nodules form [ll]. Our experience with this disease supports the impression of Thadani, Iveson and Wright [lo] that the only effective treatment of rheumatoid constrictive pericarditis is surgical pericardiectomy. All five of our patients so treated are currently asymptomatic with regard to their cardiovascular status. We conclude that rheumatoid constrictive pericardial disease is more common than is generally appreciated, Indeed, our only fatal case was rather obvious in retrospect, but the diagnosis was never considered prior to death. Since constrictive pericarditis is probably fatal if untreated, and since excellent therapy is available, we recommend that all patients with rheumatoid arthritis in whom right heart failure develops should be
COMMENTS The demonstration of five cases of serious rheumatoid pericarditis over a two and a half year period in this
considered to have pericardial disease until this diagnosis is excluded
by appropriate
studies.
REFERENCES 1.
Bonfigilio T. Atwntcr E: He;lrt tliscasc
in I)oticnts with scropositive rheumatoid arthritis: a controllctl strdy ar,tl rcview. Arch Intern Mctl 124: 714. 1969.
2.
3.
March 1979
Bywatcrs EGL: ‘l’hc rclalion Ixlwccn heart and joint tiiscase. Br Hcilrt J 12: 101, 1950. Cluickshank B: Heart lesions in rheumatoid disease. J P;lthol
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Volume 66
369
PERICARDIAL DISEASE IN RHEUMATOID ARTHRITIS-JOHN
4.
Bact 76: 223,1958. Lebowitz WB: The heart in rheumatoid arthritis, A clinical and pathological study of 62 cases. Ann Intern Med 58: 102. 1963.
5.
Kirk J, Cosh J: The pericarditis of rheumatoid arthritis. J Med 38: 397, 1969. 6. Golding JR: Rheumatoid pericarditis. Br Med J 1: 919, 1963 7. Reimer KA, Rodgers RF, Oyasu R: Rheumatoid arthritis with rheumatoid heart disease and granulomatous aortitis. JAMA 235: 2510.1976. 8. Franc0 AE, Levine HD, Hall AP: Rheumatoid pericarditis.
390
March 1979
The American Journal of Medicine
ET AL.
Report of 17 cases diagnosed clinically. Ann Intern Med 77: 837. 1972. 9. Siegmeth W, Eberl R: Gelenksferne Manifestationen Der chronischen Polyarthritis. Wien Klin Wochenschrift 88: 81. 1976. 10. Thadani U, Iveson JMI, Wright V: Cardiac tamponade, constrictive pericarditis and pericardial resection in rheumatoid arthritis. Medicine (Baltimore] 54: 261,1975. 11. Walker WC, Wright V: Diffuse interstitial pulmonary fibrosis and rheumatoid arthritis. Ann Rheum Dis 28: 252, 1969.
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