Chest
Volume 124, Issue 3, September 2003, Pages 969-977
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Clinical Investigations
PLEURA
Persistent Pleural Effusions in Primary Systemic Amyloidosis: Etiology and Prognosis

https://doi.org/10.1378/chest.124.3.969Get rights and content

Background:

Restrictive cardiomyopathy frequently complicates primary systemic amyloidosis (AL), yet only a small number of these patients develop large pleural effusions refractory to diuretic therapy and thoracentesis. We hypothesized that disruption of pleural function by amyloid deposits underlies persistent pleural effusions (PPEs) in patients with AL disease.

Methods:

We performed a retrospective study of AL patients with and without PPEs who had been referred to Boston University between 1994 and 2001. The presence of PPEs was defined by a failure to resolve the condition with thoracentesis and aggressive diuresis. AL cardiomyopathy patients without pleural effusions constituted the control (cardiac) group. Indexes of plasma cell dyscrasia, nephrotic syndrome, thyroid function, and echocardiographic measures of left and right ventricle performance were compared between groups. When available, closed needle biopsies and autopsy specimens of parietal pleura were examined for amyloid deposits.

Results:

Among 636 patients with AL, 35 PPE patients underwent a median of three thoracenteses each. No statistical differences were found between the PPE and cardiac groups in echocardiographic measures of septal thickness, left ventricular systolic function, or diastolic compliance. Right ventricular (RV) hypokinesis occurred more often in PPE patients; however, nearly half of this group had normal RV systolic function. Renal function, plasma protein levels, and thyroid function were the same between groups. Nephrotic range proteinuria (ie, > 3 g/d) was more prevalent in the cardiac group than in the PPE group (44% vs 26%, respectively; p = 0.057). All pleural biopsies in the PPE group (six biopsies) revealed amyloid deposits. Autopsy samples of parietal pleura were negative for disease in two cardiac patients. Eighteen patients had chest tubes placed, and 11 underwent pleurodesis. PPE signaled limited survival among patients who were ineligible for treatment. Untreated PPE patients lived a median 1.8 months vs 6 months for untreated cardiac patients (p = 0.031). Survival after intensive chemotherapy and autologous stem cell transplantation was comparable in the PPE and cardiac groups (21.8 vs 15.6 months, respectively; p = 0.405).

Conclusion:

In AL patients with cardiac amyloid, neither echocardiographic measures of ventricular function nor the degree of nephrosis distinguished those patients with PPEs. We conclude that pleural amyloid infiltration plays a central role in the creation and persistence of pleural effusions among patients with AL.

Section snippets

Patients

We reviewed the records of patients referred to the Amyloid Research and Treatment Program at Boston University Medical Center between 1994 and 2001 for the treatment of AL. A diagnosis of AL required demonstration of amyloid deposits by Congo red staining and detection of monoclonal Ig protein in serum, urine, bone marrow, or tissue biopsy specimen. PPEs were defined as large pleural effusions seen on a chest radiograph (occupying one third or more of the hemithorax) that persisted despite

Results

Between 1994 and 2001, 636 patients with AL were referred to the Amyloid Treatment and Research Program at Boston University Medical Center for evaluation. Thirty-five patients (6%) had large pleural effusions on screening chest radiographs that failed to resolve with direct drainage and aggressive diuresis. Five patients with PPEs had multiple myeloma, and one patient had Waldenstro¨m macroglobulinemia. One hundred twenty patients with cardiac amyloid infiltration in the absence of pleural

Discussion

Our retrospective analysis identified two statistically significant differences between AL patients with PPE and those with AL cardiac disease and no pleural effusions (ie, the cardiac group), as follows: (1) more frequent RV hypokinesis in the PPE group; and (2) greater proteinuria in patients without effusions. Multiple echocardiographic measures of LV function failed to distinguish PPE patients from those with AL cardiomyopathy alone. Taken together, the frequency of exudative pleural fluid

ACKNOWLEDGMENT

We thank Arquimedes J. Areche for expert database management, Sandra A. Cerda, MD, and Niall Swan, MD, for the histologic preparation of pleural specimens.

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:[email protected]).

    This research was supported by grants from the National Institutes of Health (HL 68705), the US Food and Drug Administration (FD-R-001346), the Gerry Foundation, the Young Family Amyloid Research Fund, the Sue Sellors Finley Cardiac Amyloid Research Fund, the Amyloid Research Fund at Boston University, and the McCaleb Foundation. Dr. Seldin is a scholar of the Leukemia and Lymphoma Society of America.

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