Abstract
The aim of this study is to investigate the clinical features and outcome of interstitial lung disease (ILD)-onset rheumatoid arthritis (RA) and anti-citrullinated protein antibody (ACPA)-positive ILD-only patients. Arthritis-onset and ILD-onset RA-ILD and ACPA-positive ILD-only patients consecutively admitted to Peking Union Medical College Hospital from January 2008 to December 2017 were enrolled and followed-up. Their demographic, clinical, and laboratory features as well as outcome were collected and analyzed. Compared with arthritis-onset RA-ILD (n = 166, median arthritis-to-ILD interval: 60 months), the ILD-onset RA-ILD (n = 75, median ILD-to-arthritis interval: 2 months) had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD (median estimated progression-free survival: 120 vs. 100 months, p = 0.019). Elder age (≥ 65 years) at ILD diagnosis and UIP pattern were associated with ILD progression by both univariate and Cox hazards modeling analysis (p < 0.05). In ACPA-positive ILD-only patients (n = 41), arthritis developed in 7 (17.1%) female patients after a median interval of 24 months. ACPA-positive ILD who subsequently developed arthritis exhibited higher frequency of rheumatoid factor (RF), higher titer of ACPA, and higher levels of ESR and CRP (p < 0.05). Multivariate regression analysis showed that positive RF (OR 12.55, 95% CI 1.31 to 120.48) was the independent risk factor for arthritis development in ACPA-positive ILD-only patients. ILD-onset RA-ILD had more stable ILD compared with arthritis-onset RA-ILD. ACPA-positive ILD patients with positive RF are at increased risk of developing RA.
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References
Wallace B, Vummidi D, Khanna D (2016) Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol 28:236–245
Shaw M, Collins BF, Ho LA et al (2015) Rheumatoid arthritis-associated lung disease. Eur Respirat Rev 24:1–16
Young A, Koduri G, Batley M et al (2007) Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology 46:350–357
Sparks JA, Chang SC, Liao KP et al (2016) Rheumatoid arthritis and mortality among women during 36 years of prospective follow-up: Results from the Nurses’ Health Study. Arthritis Care Res (Hoboken) 68:753–762
Zhang Y, Li H, Wu N et al (2017) Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol 36:817–823
Fischer A, Antoniou KM, Brown KK et al (2015) An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respirat J 46:976–987
Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588
Felson DT, Smolen JS, Wells G et al (2011) American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 70:404–413
Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry Eur Respirat J 26:319–338
Raghu G, Remy-Jardin M, Myers JL et al (2018) Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respirat Crit Care Med 198:e44–e68
Dawson JK, Fewins HE, Desmond J et al (2002) Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis. Ann Rheum Dis 61:517–521
MdYusof MY, Kabia A, Darby M et al (2017) Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centre. Rheumatology 56:1348–1357
Johnson C (2017) Recent advances in the pathogenesis, prediction, and management of rheumatoid arthritis-associated interstitial lung disease. Curr Opin Rheumatol 29:254–259
Nielen MM, van Schaardenburg D, Reesink HW et al (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50:380–386
Holers VM, Demoruelle MK, Kuhn KA et al (2018) Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. Nat Rev Rheumatol 14:542–557
Makrygiannakis D, Hermansson M, Ulfgren AK et al (2008) Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis 67:1488–1492
Paulin F, Doyle TJ, Fletcher EA et al (2015) Rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis: shared mechanistic and phenotypic traits suggest overlapping disease mechanisms. Rev Invest Clin 67:280–286
Nyhall-Wahlin BM, Turesson C, Jacobsson LT et al (2011) The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of extra-articular disease and predicts radiographic progression of joint destruction over 5 years. Scand J Rheumatol 40:81–87
Smolen JS, Aletaha D, Barton A et al (2018) Rheumatoid arthritis Nat Rev Dis Primers 4:18001
Zhu JN, Nie LY, Lu XY et al (2019) Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria? Clin Chem Lab Med 57:1668–1679
Hensvold AH, Frisell T, Magnusson PK et al (2017) How well do ACPA discriminate and predict RA in the general population: a study based on 12 590 population-representative Swedish twins. Ann Rheum Dis 76:119–125
Infantino M, Manfredi M, Meacci F et al (2014) Anti-citrullinated peptide antibodies and rheumatoid factor isotypes in the diagnosis of rheumatoid arthritis: an assessment of combined tests. Clin Chim Acta 436:237–242
Hyldgaard C, Hilberg O, Pedersen AB et al (2017) A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis 76:1700–1706
Solomon JJ, Chung JH, Cosgrove GP et al (2016) Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J 47:588–596
Adegunsoye A, Strek ME (2016) Therapeutic approach to adult fibrotic lung diseases. Chest 150:1371–1386
Burgers LE, Allaart CF, Huizinga TWJ et al (2017) Brief report: Clinical trials aiming to prevent rheumatoid arthritis cannot detect prevention without adequate risk stratification: a trial of methotrexate versus placebo in undifferentiated arthritis as an example. Arthritis Rheumatol 69:926–931
Burgers LE, Raza K, van der Helm-van Mil AH (2019) Window of opportunity in rheumatoid arthritis - definitions and supporting evidence: from old to new perspectives. RMD Open 5:e000870
Acknowledgments
We thank Yang-Zhong Zhou and Yan-Ping Wei for their advice and help.
Funding
This study was supported by grants from the National Natural Science Foundation of China (81788101, 81630044), Chinese Academy of Medical Science Innovation Fund for Medical Sciences (CIFMS2016-12M-1-003, 2017-12M-1-008, 2017-I2M-3-011, 2016-12M-1-008), Beijing Capital Health Development Fund (2020-2-4019), and the Construction Project of National Traditional Chinese Medicine Clinical Research Base of SATCM, and Clinical Cooperative Project of Chinese and Western Medicine for Major and Knotty Diseases of SATCM.
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The study was approved by the institutional ethical review board of Peking Union Medical College Hospital (approval number: JS-2034).
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Chen, RX., Zhao, LD., Xiao, XY. et al. Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases. Clinic Rev Allerg Immunol 60, 46–54 (2021). https://doi.org/10.1007/s12016-020-08819-0
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DOI: https://doi.org/10.1007/s12016-020-08819-0