REVIEW
Pleural Effusion, Pneumothorax, and Lung Entrapment in Rheumatoid Arthritis Ashwini Komarla, MD,* Gordon H. Yu, MD,† and Anupama Shahane, MD, MPH* Abstract: Rheumatoid arthritis (RA)–associated pleural effusions are usually small and asymptomatic with no need for intervention, but complex and symptomatic rheumatoid pleural effusions may be seen and are associated with significant morbidity and mortality. Pleural effusions may develop before, concurrently with, or after the joint manifestations of RA. The classic features of RA-associated pleural effusions include high cell counts and protein, lipid, and lactate dehydrogenase levels and very low glucose levels, along with distinctive cytopathologic findings: slender spindle-shaped cells, multinucleated giant cells, eosinophilic granular debris, and the absence of mesothelial cells. Rarely, rheumatoid pleural involvement can include pneumothorax or can be severe enough to progress to lung entrapment, which may cause significant restrictive lung disease and require surgical therapy. Rheumatoid pleural involvement may not always correlate with joint activity but can be a significant cause of shortness of breath for patients with RA. Key Words: lung entrapment, rheumatoid arthritis–associated lung disease, rheumatoid arthritis–associated pneumothorax, rheumatoid pleural effusions (J Clin Rheumatol 2015;21: 211–215)
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heumatoid arthritis (RA) is associated with many pleuropulmonary complications such as interstitial lung disease, rheumatoid nodules, pulmonary vascular disease, and pleural disease, in addition to drug-induced lung disease and infectious complications. Although pleural disease is the most common pulmonary manifestation in RA, it is a rare cause overall of exudative effusions. Rheumatoid pleural disease is usually clinically silent with symptomatic disease occurring in only about 5% of patients with RA.1,2 Differentiating pleural effusions as part of the underlying connective tissue disease versus a complication of immunosuppressive therapy can be challenging, and accurate diagnosis is crucial for appropriate further management. The management of RA has changed tremendously in recent years with many more therapeutic options available. We present a review of the literature on rheumatoid pleural disease and specifically cases involving biologic therapy and describe an illustrative patient with severe rheumatoid pleural disease.
METHODS A literature search was conducted using the PubMed database for articles published between January 1956 and December 2014 using the MEDLINE subheadings and key words “rheumatoid” and “pleuritis” or “pleural effusion” or “pneumothorax” and From the *Division of Rheumatology and †Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA. The authors declare no conflict of interest. Correspondence: Ashwini Komarla, MD, Division of Rheumatology, University of Pennsylvania, 8th Floor, Penn Tower, Suite 800, 3400 Civic Center Blvd, Philadelphia, PA 19104. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-1608 DOI: 10.1097/RHU.0000000000000244
“lung entrapment” and “tumor necrosis factor” or “TNF” and “pleuritis” or “pleural effusion.” Only English-language reports were reviewed. References of the studies obtained were also examined to identify additional reports.
CASE A 55-year-old man with nonerosive RA diagnosed 7 months prior was admitted to the hospital for workup of progressive shortness of breath over 4 months. At the time of diagnosis, he was noted to have synovitis with effusions in his metacarpophalangeal and proximal interphalangeal joints, knees, and metatarsophalangeal joints. Rheumatoid factor (RF) was noted to be more than 600 IU/mL with anti–cyclic citrullinated peptide antibody greater than 200 U/mL. His history was significant for a cleared hepatitis B infection with a positive hepatitis B core antibody and surface antibody and negative hepatitis surface antigen and viral DNA and hepatitis C treated with pegylated interferon α-2a with a currently undetectable hepatitis C viral RNA. The patient was thought to have contracted these through blood transfusions after a major accident 30 years ago. Human immunodeficiency syndrome screening and QuantiFERON-TB Gold (Cellestis; Victoria, Australia) assay were negative. He was administered prednisone 20 mg daily and tumor necrosis factor (TNF) α inhibitor therapy. Etanercept and adalimumab were each tried for 3 months but were stopped because of inefficacy and inability to taper his prednisone. He complained of progressive shortness of breath over the past 4 months without cough or chest pain. He had a smoking history of 60 pack-years and quit when he was diagnosed with RA. At the time of hospitalization, he was taking prednisone 20 mg daily and complained of minimal joint pain and stiffness while on that. On physical examination, vital signs were remarkable for a respiratory rate of 20 breaths/min. Pulse oximetry was 97% on room air at rest, but he desaturated to 90% with ambulation. On auscultation, decreased breath sounds were noted at the left lung base without egophany. He had minimal swelling in bilateral third and fourth metacarpophalangeal joints. No rheumatoid nodules were present. The remainder of his examination was unremarkable. Laboratory workup was unremarkable except for an erythrocyte sedimentation rate of 63 mm/h (reference range, 0–15 mm/h) and a C-reactive protein of 3.7 mg/dL (reference,
Pleural Effusion, Pneumothorax, and Lung Entrapment in Rheumatoid Arthritis Ashwini Komarla, MD,* Gordon H. Yu, MD,† and Anupama Shahane, MD, MPH* Abstract: Rheumatoid arthritis (RA)–associated pleural effusions are usually small and asymptomatic with no need for intervention, but complex and symptomatic rheumatoid pleural effusions may be seen and are associated with significant morbidity and mortality. Pleural effusions may develop before, concurrently with, or after the joint manifestations of RA. The classic features of RA-associated pleural effusions include high cell counts and protein, lipid, and lactate dehydrogenase levels and very low glucose levels, along with distinctive cytopathologic findings: slender spindle-shaped cells, multinucleated giant cells, eosinophilic granular debris, and the absence of mesothelial cells. Rarely, rheumatoid pleural involvement can include pneumothorax or can be severe enough to progress to lung entrapment, which may cause significant restrictive lung disease and require surgical therapy. Rheumatoid pleural involvement may not always correlate with joint activity but can be a significant cause of shortness of breath for patients with RA. Key Words: lung entrapment, rheumatoid arthritis–associated lung disease, rheumatoid arthritis–associated pneumothorax, rheumatoid pleural effusions (J Clin Rheumatol 2015;21: 211–215)
R
heumatoid arthritis (RA) is associated with many pleuropulmonary complications such as interstitial lung disease, rheumatoid nodules, pulmonary vascular disease, and pleural disease, in addition to drug-induced lung disease and infectious complications. Although pleural disease is the most common pulmonary manifestation in RA, it is a rare cause overall of exudative effusions. Rheumatoid pleural disease is usually clinically silent with symptomatic disease occurring in only about 5% of patients with RA.1,2 Differentiating pleural effusions as part of the underlying connective tissue disease versus a complication of immunosuppressive therapy can be challenging, and accurate diagnosis is crucial for appropriate further management. The management of RA has changed tremendously in recent years with many more therapeutic options available. We present a review of the literature on rheumatoid pleural disease and specifically cases involving biologic therapy and describe an illustrative patient with severe rheumatoid pleural disease.
METHODS A literature search was conducted using the PubMed database for articles published between January 1956 and December 2014 using the MEDLINE subheadings and key words “rheumatoid” and “pleuritis” or “pleural effusion” or “pneumothorax” and From the *Division of Rheumatology and †Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA. The authors declare no conflict of interest. Correspondence: Ashwini Komarla, MD, Division of Rheumatology, University of Pennsylvania, 8th Floor, Penn Tower, Suite 800, 3400 Civic Center Blvd, Philadelphia, PA 19104. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-1608 DOI: 10.1097/RHU.0000000000000244
“lung entrapment” and “tumor necrosis factor” or “TNF” and “pleuritis” or “pleural effusion.” Only English-language reports were reviewed. References of the studies obtained were also examined to identify additional reports.
CASE A 55-year-old man with nonerosive RA diagnosed 7 months prior was admitted to the hospital for workup of progressive shortness of breath over 4 months. At the time of diagnosis, he was noted to have synovitis with effusions in his metacarpophalangeal and proximal interphalangeal joints, knees, and metatarsophalangeal joints. Rheumatoid factor (RF) was noted to be more than 600 IU/mL with anti–cyclic citrullinated peptide antibody greater than 200 U/mL. His history was significant for a cleared hepatitis B infection with a positive hepatitis B core antibody and surface antibody and negative hepatitis surface antigen and viral DNA and hepatitis C treated with pegylated interferon α-2a with a currently undetectable hepatitis C viral RNA. The patient was thought to have contracted these through blood transfusions after a major accident 30 years ago. Human immunodeficiency syndrome screening and QuantiFERON-TB Gold (Cellestis; Victoria, Australia) assay were negative. He was administered prednisone 20 mg daily and tumor necrosis factor (TNF) α inhibitor therapy. Etanercept and adalimumab were each tried for 3 months but were stopped because of inefficacy and inability to taper his prednisone. He complained of progressive shortness of breath over the past 4 months without cough or chest pain. He had a smoking history of 60 pack-years and quit when he was diagnosed with RA. At the time of hospitalization, he was taking prednisone 20 mg daily and complained of minimal joint pain and stiffness while on that. On physical examination, vital signs were remarkable for a respiratory rate of 20 breaths/min. Pulse oximetry was 97% on room air at rest, but he desaturated to 90% with ambulation. On auscultation, decreased breath sounds were noted at the left lung base without egophany. He had minimal swelling in bilateral third and fourth metacarpophalangeal joints. No rheumatoid nodules were present. The remainder of his examination was unremarkable. Laboratory workup was unremarkable except for an erythrocyte sedimentation rate of 63 mm/h (reference range, 0–15 mm/h) and a C-reactive protein of 3.7 mg/dL (reference,
