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Bilateral Pleural Effusions as the Initial Manifestation of Rheumatoid Arthritis

Published:November 06, 2022DOI:https://doi.org/10.1016/j.amjmed.2022.10.005
      To the Editor:
      Rheumatoid arthritis has a well-established association with pulmonary manifestations, including pleural effusions. However, only 3%-5% of pleural effusions are known to be symptomatic and are frequently unilateral.
      • Shaw M
      • Collins BF
      • Ho LA
      • Raghu G
      Rheumatoid arthritis-associated lung disease.
      Herein, we present an atypical case of a patient with respiratory failure found to have bilateral pleural effusions as the initial presenting manifestation of rheumatoid arthritis.

      Case Report

      A 66-year-old Caucasian man with a past medical history of emphysema and a 50-pack-year smoking history presented with progressive shortness of breath for 4 months. A physical examination was unremarkable aside from mild/moderate respiratory distress and decreased breath sounds in lungs bilaterally. No rashes or joint swelling were present. Labs showed a normal complete blood count and basic metabolic panel. A computed tomography scan of the thorax was notable for bilateral pulmonary effusions that were greater on the right with underlying emphysema and pulmonary nodules (Figure). A thoracentesis with fluid studies showed an elevated pleural-fluid-to-serum-fluid ratio of 5:6.6 g/dL, a low glucose of <20 mg/dL, and a high pleural-to-serum lactate dehydrogenase ratio of 6,450:441 U/L, which were all consistent with an exudative process. Multiple cytology studies and lymph node biopsies were negative for any malignancy. An autoimmune work-up showed positive serologies for antinuclear antibody (1:320 titer, homogenous pattern), a rheumatoid factor of 291 (N <20), and a cyclic citrullinated peptide (CCP) antibody of 171 (N <20). Hepatitis C virus, anti-SSA, anti-SSB, anti-DNA, and anti-Smith antibodies were all negative. The high-titer positive serologies for rheumatoid arthritis and characteristic exudative pleural effusion pointed to a final diagnosis of a rheumatoid arthritis-associated effusion. The patient was started on hydroxychloroquine 400 mg daily; however, at a follow-up 1 week later, he had evidence of synovitis at numerous metacarpophalangeal joints. Therefore, an oral prednisone taper plus oral sulfasalazine was added, with subsequent improvement.
      Figure
      Figure(A, B) Bilateral pleural effusion seen on computed tomography of the lung, with right side greater than left. (C) Photo of bilateral hands showing multiple, left-sided metacarpophalangeal joint synovitis and dorsal hand swelling, which manifested after pleural effusion had developed.

      Discussion

      Most cases of rheumatoid arthritis present with arthralgias in symmetric non-weight-bearing joints, involving joint swelling and prolonged morning stiffness. Extra-articular manifestations typically arise a few years after the initial presentation, with pulmonary manifestations arising within the first 5 years of disease onset and interstitial lung disease being the most common pulmonary sequela.
      • Shaw M
      • Collins BF
      • Ho LA
      • Raghu G
      Rheumatoid arthritis-associated lung disease.
      ,
      • Azam AT
      • Odeyinka O
      • Alhashimi R
      • et al.
      Rheumatoid arthritis and associated lung diseases: a comprehensive review.
      Although rheumatoid arthritis is more common in women, rheumatoid arthritis-related lung disease has a predilection for males, with twice as many male patients as females presenting with pulmonary symptoms. High-titer rheumatoid factor, high-titer anti-CCP, and HLA-B8 and DW3 are highly associated with rheumatoid arthritis pleural effusions. They have an annual incidence of 0.34% in women and 1.54% in men, and are usually asymptomatic, small, and unilateral.
      • Kadura S
      • Raghu G
      Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management.
      ,
      • Balbir-Gurman A
      • Yigla M
      • Nahir AM
      • Braun-Moscovici Y
      Rheumatoid pleural effusion.
      Fluid studies are usually consistent with an exudative effusion consisting of a high protein count, elevated lactate dehydrogenase, low glucose, and low pH.
      • Sølling Avnon L
      • Abu-Shakra M
      • Flusser D
      • Heimer D
      • Sion-Vardy N
      Pleural effusion associated with rheumatoid arthritis: what cell predominance to anticipate?.
      Rheumatoid nodules that occur from persistent inflammation are thought to be responsible for the increased permeability in pleural cavities that leads to fluid accumulation in the setting of rheumatoid arthritis.
      • Yunt ZX
      • Solomon JJ
      Lung disease in rheumatoid arthritis.
      Treatment consists of long-term immunotherapy, with some consideration toward antifibrotic agents.
      • Kadura S
      • Raghu G
      Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management.

      Conclusion

      It is important to consider all causes of exudative pleural effusions by completing a thorough infectious and malignant workup. Although rare, pleural manifestations preceding articular symptoms of rheumatoid arthritis have been observed, but frequently self-resolve.
      • Yunt ZX
      • Solomon JJ
      Lung disease in rheumatoid arthritis.
      Mainstay of treatment remains smoking cessation, oxygen supplementation, and treatment of underlying comorbidities.

      Acknowledgment

      We thank Ty Bohrnstedt for his expertise and assistance with technical editing, proofreading, and image editing for this manuscript.

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