Pulmonary amyloidosis is an uncommon etiology of transudative pleural effusions especially in absence of left ventricular dysfunction. Here we describe a case of transudative pleural effusions, pulmonary hypertension with cor pulmonale and infiltrative cardiomyopathy from Primary Amyloidosis(AL).
A 69-year-old woman, non-smoker with a history of Mitral valve prolapse(MVP) with complaint of exertional dyspnea for a few months was referred to a pulmonologist for work-up of pulmonary hypertension. CT Chest, HIV serology and rheumatological work up was negative. Cardiac catheterization revealed normal coronaries, no MR, LVEF 70%, mPAP-35, PCWP-18, LVEDP-13, mRAP-13, PVR-7.63 woods, CI-2.23 with negative vasoreactivity to nitric oxide. Two weeks later, patient was hospitalized for worsening dyspnea, pedal edema and cough. Physical examination revealed low oximetry 92%RA, JVD, decreased breath sounds bibasally, a mitral-valve-click without murmur and 3+pedal edema. Her labs were significant for an elevated WBC(14,000/mm3), Thrombocytopenia (96,000/mm3), elevated BUN/creatinine-54/1.6mg/dl, BNP-9066 and markedly abnormal LFTs: AST-3270U/L, ALT-4540U/L. Hepatitis serology and RUQ-ultrasound were negative. CXR revealed moderate bilateral pleural effusions. She underwent right thoracentesis. Pleural fluid was transudative: pH-7.67, Total Protein-2.4g/dl, LDH-207U/L, ratios of 0.44 and 0.31 respectively, Glucose-121g/dl, amylase-47 U/L, Triglycerides-41. Echocardiogram now revealed normal LVEF, mild MR, severe right atrial and ventricular enlargement, severe TR, pulmonary hypertension(PASP-86). A speckled appearance of myocardium was noted. CT angiogram of chest ruled out thromboembolic disease and confirmed the effusions. Cardiac MRI revealed biatrial enlargement with delayed hyperenhancement in inferior and inferoseptal regions of LV, in a subepicardial distribution suggesting an infiltrative cardiomyopathy with no wall motion abnormality. SPEP showed hypogammaglobulinemia, UPEP demonstrated Bence Jones proteins (lambda-type light chains). A fat pad biopsy confirmed diagnosis of Amyloidosis. The patient was aggressively diuresed with improvement in her condition. Outpatient bone marrow biopsy was advised to rule out plasma cell dyscrasia.
Amyloidosis is a family of diseases caused by the overexpression of proteins that deposit as insoluble beta-pleated fibrils in tissues disrupting organ function. The most frequent types include AL(primary) and AA(secondary). Pulmonary amyloidosis is seen commonly in AL type. It may manifest as tracheobronchial infiltration, parenchymal nodules(amyloidomas); rarely it may cause pleural effusions and pulmonary hypertension. In 2003, the Amyloid Program at Boston University reported that 6% of 636 AL type patients seen over a 7-year period presented with large, persistent pleural effusions and 10–15% with small effusions. In contrast, none of 223 AA amyloid autopsy cases at Johns Hopkins reported any effusions. The most recent review by Berk included 23 cases of effusion, 21 of which documented pleural amyloid infiltration; 65% had AL-type. CHF accompanied the effusions in 80%, of these 42% were exudative, 42% were transudative, and 18% indeterminate. All three AL cases without CHF were exudative suggesting amyloid deposits disrupting the pleural surface. Amyloid-induced cardiomyopathy often accompanies effusions in the AL-type. However extensive echocardiographic data from the Boston review failed to establish a causal relationship between LV function or diastolic filling and pleural effusions, although diastolic dysfunction from amyloid infiltration, can theoretically raise filling pressures and induce pulmonary edema or effusions. Hence cardiac dysfunction alone is not sufficient to produce pleural effusions. A trend toward higher PASP and RV dilatation was detected in those with pleural effusions. This represents ALamyloid-induced pulmonary vascular disease. Berk also illustrated that nephrotic-range proteinuria, hypoalbuminemia or thyroid dysfunction did not induce effusions. Amyloid infiltration of the parietal pleura is therefore the likely etiology. This is supported by thoracoscopic descriptions of amyloid pleural deposits and evidence of amyloid infiltration on histopathology.
Primary Amyloidosis(AL) is a rare cause of pleural effusions and pulmonary hypertension. Patients with AL-disease often have evidence of infiltrative cardiomyopathy that is contributive but not sufficient for the creation of the effusions.
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