Rare Disease Causing Constriction

Apr 29, 2019   |  Johnny Chahine, MD; Chandra Kanth Ala, MD; Carmela D. Tan, MD; James L Gentry, MD, FACC; Allan L. Klein, MD, CM, FACC
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A 54-year-old female originally from Arequipa (Southern Peru) with a past medical history of pericarditis, interstitial lung disease, peripheral arterial disease, peripheral neuropathy, hypoalbuminemia and complicated gastrointestinal history (gastric bypass surgery, bowel obstruction due to adhesions, left hemicolectomy and contaminated blind loop syndrome) presented with sudden onset chest pain. This pain is diffuse, non-irradiating, worse on inspiration, relieved on bending forward, associated with dyspnea at rest, orthopnea and leg swelling. She denies palpitations, dizziness, chest trauma, fever, chills, cough or personal history of autoimmune diseases.

The patient was admitted three years previously for similar symptoms and was diagnosed with pneumonitis and acute pleuropericarditis; autoimmune and infectious workup was negative. Pericardiocentesis and thoracentesis then were negative for malignant or inflammatory cells. Pericardial biopsy showed mild to moderate interstitial fibrosis and lung, and pleural biopsy showed fibrosis with evidence of acute on chronic inflammation. A recent computed tomography of the chest and abdomen before admission revealed thickened pulmonary interlobular septa, mild pleural thickening, bilateral thickening of the perirenal soft tissues, bilateral hydronephrosis, dilated intrahepatic and extrahepatic biliary ducts and thick fibrotic tracts in the pleural, retroperitoneum and mesentery.

The patient did not have a recurrence of her chest pain; however, she endorses decreased exercise tolerance since then. On presentation, the patient was hemodynamically stable. On physical exam, the patient had positive a Kussmaul's sign, pericardial rub, hepatomegaly and bilateral lower extremity swelling. She had leukocytosis (white blood cell count of 16.5 k/uL, normal: 3.70 - 11 k/uL), elevated erythrocyte sedimentation rate (48 mm/hour, normal: 10- 20 mm/hour) and C-reactive protein (17.3 mg/dL, normal: <0.9 mg/dL). An echocardiogram was done for suspicion of acute pericarditis/pericardial constriction and showed moderate circumferential pericardial effusion with signs of constrictive physiology (significant/reciprocal respiratory ventricular filling variation, inferior vena cava of 2 cm with inspiratory collapse less than 50%) and thickened pericardium. A pericardial window was then attempted however failed due to thick pericardium and adhesions. However, a pericardial biopsy was still obtained, and pathology revealed non-specific chronic pericarditis with fibrinous exudates. The patient was started on furosemide 20 mg oral daily, colchicine 0.3 mg orally twice daily and prednisone 60 mg orally twice daily.

After discharge, the patient endorsed only mild relief of her symptoms with persistent pleuritic chest pain and continued decreased exercise tolerance. A cardiac magnetic resonance was performed one month after discharge and showed severe circumferential thickening of the pericardium (of 12 mm), circumferential pericardial and pleural delayed gadolinium enhancement, trivial pericardial effusion and no overt signs of pericardial constriction (Figures 1 and 2). A radical pericardiectomy was then performed for chronic recurrent pericarditis. Pathology of the pericardial sample showed diffuse infiltration of histiocytes, positive BRAF V600E mutation, positive immunoreactivity of the histiocytes for CD68, CD163, and factor XIIIa, and negative staining with S100 protein, langerin, and CD1a (Figures 3 and 4). A whole-body technetium bone scan revealed an intense symmetrically increased uptake involving the maxillae, bilateral distal femurs, entire tibiae and fibulae as well as the bilateral radii and ulnae (Figure 5).

After discharge, vemurafenib was started, a recently FDA approved BRAF inhibitor to treat the patient's underlying disease.

Figure 1

Figure 1
Figure 1: Four chamber phase-sensitive inversion recovery cardiac magnetic resonance imaging showing delayed enhancement of the pericardium (orange arrows) and pleura (red arrows).

Figure 2

Figure 2
Figure 2: T2 short-tau inversion recovery weighted cardiac magnetic resonance imaging showing edema of the pericardium (orange arrow).

Figure 3

Figure 3
Figure 3: Pathology of the pericardial sample showing diffuse infiltration of histiocytes (black arrow) on hematoxylin and eosin stain (on the left) and positive BRAF V600E mutation on immunostaining (in brown, on the right).

Figure 4

Figure 4
Figure 4: Positive immunoreactivity of the histiocytes for CD68, CD163, and factor XIIIa (in brown), and negative staining with S100 protein and Langerin.

Figure 5

Figure 5
Figure 5: A whole body technetium bone scan showing intense symmetrically increased uptake involving the maxillae, bilateral distal femurs, entire tibiae and fibulae, as well as the bilateral radii and ulnae (white arrows).

Based on the clinical presentation and the pathology results, which of the following would be the most likely diagnosis?

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