Hemorrhagic pericardial effusion as a presenting symptom of newly diagnosed rheumatoid arthritis

Hemorrhagic pericardial effusion as a presenting symptom of newly diagnosed rheumatoid arthritis

Pericardial effusion, whether transudative, exudative, or sanguineous, is present in up to 6.5% of the current general population in the United States. [1]. The most common etiologies of new-onset hemorrhagic pericardial effusion are malignancy, infectious causes, rheumatologic disease, and trauma. Systemic lupus erythematosus, rheumatoid arthritis (RA), and Sjogren’s syndrome are among the most common rheumatologic and inflammatory culprits. With a lifetime risk of 3.6% in women and 1.7% in men, RA leads to progressive disability and morbidity in a large subset of patients [2]. When evaluating RA, diagnosis can be challenging given the varied clinical presentation, as well as the lack of consensus on a pathognomonic laboratory test worldwide. In patients with confirmed RA, it is estimated that the presence of pericardial effusions can be found in up to 30% of patients with confirmed RA [3]. These pericardial effusions are typically exudative in nature with low glucose concentrations and complement 3 and complement 4 levels. In addition, the fluid often shows high levels of lactate dehydrogenase (LDH) and gamma globulin concentrations. RA leads to hemorrhagic pericardial effusion only in very rare cases, and hemorrhagic pericardial effusion as a presenting symptom is even rarer.

In the recent research literature, several studies and reviews have explored the relationship between RA and pericardial effusions. One of these studies involved an echocardiographic analysis of 101 randomly selected RA patients that identified the prevalence of cardiac abnormalities among RA patients. Thirty-one patients were found to have 45 echocardiographic abnormalities and five patients had pericardial effusion. [4]. In another systematic review, RA demonstrated a significant association with pericardial effusion, with an odds ratio of 10.7 and a 95% confidence interval of 5.0 to 23.0 [5]. More specifically, when observing different alterations in echocardiography in patients with RA in the absence of symptoms of heart disease, Corrao et al. identified posterior pericardial effusion, aortic root abnormalities, and valve thickening as the most common findings [6]. In current clinical practice, knowledge about the presence of unrecognized cardiac abnormalities may be crucial for accurate evaluation and treatment of RA patients. We describe the case of a patient who presented with an unusual type of hemorrhagic pericardial effusion secondary to undiagnosed RA.

A 58-year-old woman presented to the emergency department with chest pain and shortness of breath two days after drainage of her peritoneal inclusion cyst. She had 2 days’ duration of pleuritic chest pain with associated shortness of breath. In the ED, she reported moderate lower abdominal pain, occasional bilateral knee pain, chronic left wrist numbness, and left hand pain. Her prior medical history was notable for hypertension, stage 3A chronic kidney disease, hypothyroidism, depression, and multiple abdominal surgeries with segments of intestine removed as a consequence of a benign ovarian mass that led to omental hardening with subsequent intestinal obstruction. Systems review was positive for fatigue, dyspnea, chest pain, nausea, abdominal pain, chronic hematuria, occasional arthralgia, and dizziness. She recently had a low-grade fever of 100.1˚F for one day, tachycardia of 110 beats per minute, normal respiratory rate, oxygen saturation of 97% on room air, and blood pressure of 136/79 mmHg. Follow-up electrocardiograms revealed atrial flutter with predominant 2:1 AV block, ST-segment elevation in the lateral leads, and prolonged QTc in 519. Chest computed tomography revealed a large pericardial effusion (measuring 1.5 cm anterior , 2.21 cm in the back and 2.5 cm). cm laterally) (Figure 1). A transthoracic echocardiogram was performed, which showed a normal-sized left ventricle, left ventricular systolic dysfunction with ejection fraction of 40-45%, mildly dilated left atrium, mild aortic regurgitation, moderate aortic stenosis, and significant pericardial effusion (Figures 2A, 2B). Vagal maneuvers broke the arrhythmia and the patient returned to normal sinus rhythm.

The patient was admitted to the cardiology service and a diagnostic pericardiocentesis was performed, which revealed a hemorrhagic pericardial effusion. Pericardial fluid analysis showed an elevated white blood cell count of 1400 CUMM, glucose 133 mg/dL, protein 5 g/dL, albumin 2.6 g/dL, LDH 930 U/L, pH 7 ,34 and red blood cell count of 401,000 CUMM. An in situ drain was left, which drained more than 500 mL on the first day, and was later removed on the third day when the volume threshold for extraction was reached. A repeat transthoracic echocardiogram was performed, which showed a significant reduction in pericardial effusion and an improved ejection fraction of 50-55%. Bacterial cultures, Gram stains, fungal cultures, and acid-fast cultures of pericardial fluid were negative. Cytology was negative for malignancy, as was CEA, CA19-9, and CA125. Anti-CREST, anti-Scl70, anti-SSA, anti-SSB, anti-dsDNA, anti-Smith, anti-HCV, anti-Jo1, anti-Ku, anti-Mi-2, ANA, HLA-B27, complement 3 , complement 4, RP, p155/140, pANCA, PL-7, PL-12, anti-Scl100, anti-SRP, anti-RNP, anti-SAE 1, anti-NXP, anti-MDA, TIF 1-gamma, and myositis panels were within normal limits. Rheumatoid factor and anticyclic citrullinated peptide were positive at 1128 IU/mL and 220 U, respectively. In addition, antiproteinase 3 (cANCA) was positive at 20 AU/mL, as was IgA at 469 mg/dL and IgG4 at 155 mg/dL.

Hemorrhagic pericardial effusion secondary to RA was diagnosed and treatment was started with disease-modifying antirheumatic drugs (DMARDs) in the form of weekly methotrexate and folic acid. Her symptoms resolved shortly thereafter and the patient underwent sclerotherapy for prevention of recurrence of the inclusion cysts.

The most common cardiac manifestation of RA is pericarditis, which can occasionally cause exudative pericardial effusions. However, these are rarely the presenting signs of undiagnosed RA. Since pericarditis and pericardial effusions are associated with higher mortality rates in RA patients, it is important to include immunological etiologies in the differentials. [7]. Even more rare is RA-associated hemorrhagic pericardial effusion with normal glucose and normal complement 3/4 levels as a presenting sign of undiagnosed RA.

The most common causes of hemorrhagic pericardial effusions are malignancies, infections, trauma, and immunology/autoimmunity. In cases where there is no known cause based on history and no obvious infectious etiology, RA should be included in the differentials and workup. The absence of clear joint disease should also not rule out RA, nor does the degree of joint disease appear to influence the likelihood of pericarditis and pericardial effusion. [8,9]. It should also be noted that the administration of TNF-alpha inhibitors for pre-existing RA does not appear to reduce the risk of pericardial effusions. [8]. A thorough workup should be performed for each of the above etiologies, as pericardial effusions are likely to recur and may cause tamponade. Pericardial fluid should be collected and analyzed, especially if there is a significant accumulation of fluid. However, as emphasized in this case, fluid analysis is not always the most reliable method for differentiating between etiologies; for example, traditional pericardial fluid analysis for most cases of RA-induced pericardial effusion shows minimal red blood cells, low glucose, low complement C3 and C4, elevated LDH, elevated gamma globulin, and elevated leukocytes [3]. In our case, there was a marked elevation of red blood cells and glucose was unusually normal, as was complement C3, C4 and gamma globulin.

RA-induced pericardial effusion can often present with tamponade, as the initial fluid collection is usually asymptomatic. The research literature indicates that indolent fluid collection typically takes more volume to cause tamponade than acute fluid collection. This makes new acute flares of RA with large pericardial effusions particularly dangerous, as fluid accumulation is more rapid and more likely to lead to pericardial tamponade. [10]. Paradoxically, once the diagnosis is made, RA-induced pericardial effusions respond well to treatment with pericardiocentesis followed by NSAIDs or colchicine as needed.

Early diagnosis and initiation of medical treatment for RA are essential to reduce the risk of irreversible damage to multiple organ systems in these patients. In the absence of the typical clinical manifestations of RA, our case serves as a reminder to maintain a high clinical suspicion of RA in the presence of more unusual cardiac findings, including hemorrhagic pericardial effusions. This case specifically demonstrates the importance of considering hemorrhagic pericardial effusion as a marker of undiagnosed RA, especially if malignant or traumatic causes have been ruled out.

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