February 2021 — Transfusion Medicine Case 2
A 72-year-old man with a past medical history of polymyositis managed with IVIG presents with worsening dyspnea on exertion. He presented to the emergency department and was noted to have oxygen saturations at 83%. A computed tomography scan demonstrates newly developed diffuse, bilateral ground glass opacities. He was admitted and placed on 4L supplemental oxygen, but gradually declined despite standard immunosuppressive care, ultimately requiring mechanical ventilation support. IgG anti-Jo1 levels were noted at >8.0 U.
What is the most likely diagnosis and what is a potential next step in therapeutic intervention?
- Anti-synthetase syndrome with associated interstitial lung disease. Therapeutic plasma exchange should be started.
- Cryptogenic organizing pneumonia. Bronchoalveolar lavage with culture and drug specificities should be done.
- Mucinous lung adenocarcinoma. Wedge biopsy with histological evaluation.
- Usual interstitial pneumonia. Wedge biopsy with histological evaluation and pulmonary function testing.
The correct answer is ...
The diagnosis in this case is: Anti-synthetase syndrome with associated interstitial lung disease. Therapeutic plasma exchange should be started.
This is a case of anti-synthetase syndrome with associated interstitial lung disease. The classic example of this disease is polymyositis with anti-Jo1 antibodies. This general diagnosis encompasses many rheumatologic diseases characterized by inflammatory muscle disease, pulmonary and joint inflammation, interstitial lung disease, and anti-synthetase antibodies such as anti-Jo1, -SSA, -Smith/RNP, -PL7/12, -EJ, -OJ, -SRP, -Ku, -SCL-100, -Fibrillarin, -Mi-2, -P155/140, -TIF-1 gamma, -SAE1, -NXP2, and -MDA5. Current first-line therapy includes corticosteroids or other immunosuppressive agents, which are often used in combination.
Dermatomyositis/polymyositis, two examples of anti-synthetase associated syndromes, are category IV indications for therapeutic plasma exchange (TPE) according to the 2019 American Society for Apheresis guidelines. Category IV indications for apheresis are “disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful.” Category I indications for apheresis are “disorders for which apheresis is accepted as first-line therapy, either as a primary stand-alone treatment or in conjunction with other modes of treatment.” Category II indications are “disorders for which apheresis is accepted as second-line therapy, either as a stand-alone treatment or in conjunction with other modes of treatment.” Current guidelines for dermatomyositis/polymyositis focus on treatment of cell mediated tissue damage without recommendations for antibody mediated disease. As such, TPE for anti-synthetase syndrome with interstitial lung disease is better described as an uncategorized indication for TPE.
A recent body of case reports demonstrates effective intervention with therapeutic plasma exchange or column filtration plasmapheresis in individuals with anti-synthetase syndromes with interstitial lung disease resistant to medical management. At the time of publication, the ASFA guidelines considered inclusion of a fact sheet for anti-synthetase syndrome for which identifiable antibodies are detected in the setting of interstitial lung disease. Of the cases reported in the literature, stabilization of or improvement in respiratory function and chest radiograph findings has been documented in most cases. This is a disease category for which the role of apheresis is evolving, and further recommendations for intervention will hopefully be included in the next iteration of the ASFA guidelines.
- Yamagata, A, Arita, M, Tanaka, A, et al. Therapeutic plasma exchange for clinically amyopathic dermatomyositis (CADM) associated with rapidly progressive interstitial pneumonia. J Clin Apher. 2020; 35: 435– 443.
- Bozkirli, D. E., Kozanoglu, I., Bozkirli, E. & Yucel, E. Antisynthetase syndrome with refractory lung involvement and myositis successfully treated with double filtration plasmapheresis. J Clin Apher 28, 422-425, doi:10.1002/jca.21285 (2013).
- Huang, J. et al. Combined usage of extracorporeal membrane oxygenation and double filtration plasmapheresis in amyopathic dermatomyositis patient with severe interstitial lung disease: A case report. Medicine (Baltimore) 97, e10946, doi:10.1097/MD.0000000000010946 (2018).
- Imbert-Masseau, A., Hamidou, M., Agard, C., Grolleau, J. Y. & Cherin, P. Antisynthetase syndrome. Joint Bone Spine 70, 161-168 (2003).
- Omotoso, B. A., Ogden, M. I. & Balogun, R. A. Therapeutic plasma exchange in antisynthetase syndrome with severe interstitial lung disease. J Clin Apher 30, 375-379, doi:10.1002/jca.21387 (2015).
- Padmanabhan, A, Connelly‐Smith, L, Aqui, N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019; 34: 171–354. https://doi.org/10.1002/jca.21705
Thomas Thompson, M.D.
Fellow, Transfusion Medicine
Jeffrey Winters, M.D.
Consultant, Transfusion Medicine
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science