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Ramien R, Rudi T, Alten R, Krause A, Schneider M, Schaefer M, Strangfeld A, Meissner Y. Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis - a nested case-control study within the German biologics register RABBIT. Arthritis Res Ther 2024; 26:209. [PMID: 39639378 PMCID: PMC11619653 DOI: 10.1186/s13075-024-03449-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 12/01/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). METHODS We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. RESULTS We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97-1.40] and 1.06 [0.86-1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35-2.57]) and log CRP (1.55 [1.21-1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. CONCLUSION Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient's global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.
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Affiliation(s)
- Ronja Ramien
- Epidemiology and Health Services Research, German Rheumatology Research Center, Charitéplatz 1, 10117, Berlin, Germany
- Privataerztliches Zentrum am Roseneck, Berlin, Germany
| | - Tatjana Rudi
- Epidemiology and Health Services Research, German Rheumatology Research Center, Charitéplatz 1, 10117, Berlin, Germany
| | - Rieke Alten
- Schlosspark-Klinik Charlottenburg, Berlin, Germany
| | | | | | - Martin Schaefer
- Epidemiology and Health Services Research, German Rheumatology Research Center, Charitéplatz 1, 10117, Berlin, Germany
| | - Anja Strangfeld
- Epidemiology and Health Services Research, German Rheumatology Research Center, Charitéplatz 1, 10117, Berlin, Germany
- Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany
| | - Yvette Meissner
- Epidemiology and Health Services Research, German Rheumatology Research Center, Charitéplatz 1, 10117, Berlin, Germany.
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Sullivan DI, Ascherman DP. Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): Update on Prevalence, Risk Factors, Pathogenesis, and Therapy. Curr Rheumatol Rep 2024; 26:431-449. [PMID: 39320427 DOI: 10.1007/s11926-024-01155-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2024] [Indexed: 09/26/2024]
Abstract
PURPOSE OF REVIEW Rheumatoid arthritis is frequently complicated by interstitial lung disease (RA-ILD), an underappreciated contributor to excess morbidity and mortality. The true prevalence of RA-ILD is difficult to define given the variability in diagnostic criteria used. The lack of standardized screening methods, an incomplete understanding of disease pathogenesis, and dearth of validated biomarkers have limited the development of controlled clinical trials for this disease. RECENT FINDINGS Numerous studies have focused on clinical, radiographic, genetic, molecular, and/or serologic markers of disease severity as well as risk of disease progression. In addition to defining valuable clinical biomarkers, these studies have provided insights regarding the pathogenesis of RA-ILD and potential therapeutic targets. Additional studies involving immunomodulatory and/or anti-fibrotic agents have assessed new therapeutic options for different stages of RA-ILD. RA-ILD continues to be a major contributor to the increased morbidity and mortality associated with RA. Advancements in our understanding of disease pathogenesis at a molecular level are necessary to drive the development of more targeted therapy.
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Affiliation(s)
- Daniel I Sullivan
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, UPMC Montefiore Hospital, 3459 Fifth Ave, NW 628, Pittsburgh, PA, 15213, USA.
| | - Dana P Ascherman
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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Kim SC, Park HC, Lee KH. Perioperative Considerations for Hip Arthroplasty in Patients with Rheumatoid Arthritis. Hip Pelvis 2024; 36:250-259. [PMID: 39620566 PMCID: PMC11638756 DOI: 10.5371/hp.2024.36.4.250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/11/2024] [Accepted: 01/11/2024] [Indexed: 12/15/2024] Open
Abstract
Due to its distinct features, rheumatoid arthritis (RA), an inflammatory autoimmune disorder, poses challenges in planning for surgical interventions. This review includes available evidence regarding perioperative considerations in management of RA patients, with a focus on hip surgery. RA can affect multiple joints, with development of extra-articular manifestations; therefore, preoperatively, comprehensive medical assessments, including cardiovascular or pulmonary evaluation must be considered in addition to surgical considerations. Modification of medications capable of controlling RA-related disease activity is critical, and requires collaboration with rheumatologists. Surgical considerations include the choice of surgical approach, implant selection, and problems related to weakened soft tissues, fragile bone density, and bony deformity such as protrusio acetabuli. Careful monitoring and more active rehabilitation are recommended for RA patients due to higher risk of postoperative complications. For achievement of optimal outcomes, use of a multidisciplinary perioperative approach is required for patients with RA.
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Affiliation(s)
- Seung-Chan Kim
- Department of Orthopedic Surgery, Eunpyeong St. Mary’s Hospital, School of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyung Chul Park
- Department of Orthopedic Surgery, Seoul St. Mary’s Hospital, School of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyung-Hag Lee
- Department of Orthopedic Surgery, National Medical Center, Seoul, Korea
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4
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David M, Dieude P, Debray MP, Le Guen P, Crestani B, Borie R. [Low-dose methotrexate: Indications and side effects, particularly in cases of diffuse interstitial pneumonia]. Rev Mal Respir 2024; 41:605-619. [PMID: 39025770 DOI: 10.1016/j.rmr.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 06/09/2024] [Indexed: 07/20/2024]
Abstract
INTRODUCTION Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use. STATE OF THE ART In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD). PERSPECTIVES AND CONCLUSIONS Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment.
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Affiliation(s)
- M David
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France.
| | - P Dieude
- Université Paris Cité, Inserm, PHERE, 75018 Paris, France; Service de rhumatologie A, hôpital Bichat, AP-HP, Paris, France
| | - M P Debray
- Service de radiologie, hôpital Bichat, AP-HP, Paris, France
| | - P Le Guen
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France
| | - B Crestani
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France
| | - R Borie
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France
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5
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Ermencheva P, Kotov G, Shumnalieva R, Velikova T, Monov S. Exploring the Role of the Microbiome in Rheumatoid Arthritis-A Critical Review. Microorganisms 2024; 12:1387. [PMID: 39065155 PMCID: PMC11278530 DOI: 10.3390/microorganisms12071387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/27/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
Rheumatoid arthritis (RA) is a chronic, autoimmune rheumatic disease characterized by synovial joint inflammation with subsequent destruction as well as systemic manifestation, leading to impaired mobility and impaired quality of life. The etiopathogenesis of RA is still unknown, with genetic, epigenetic and environmental factors (incl. tobacco smoking) contributing to disease susceptibility. The link between genetic factors like "shared epitope alleles" and the development of RA is well known. However, why only some carriers have a break in self-tolerance and develop autoimmunity still needs to be clarified. The presence of autoantibodies in patients' serum months to years prior to the onset of clinical manifestations of RA has moved the focus to possible epigenetic factors, including environmental triggers that could contribute to the initiation and perpetuation of the inflammatory reaction in RA. Over the past several years, the role of microorganisms at mucosal sites (i.e., microbiome) has emerged as an essential mediator of inflammation in RA. An increasing number of studies have revealed the microbial role in the immunopathogenesis of autoimmune rheumatic diseases. Interaction between the host immune system and microbiota initiates loss of immunological tolerance and autoimmunity. The alteration in microbiome composition, the so-called dysbiosis, is associated with an increasing number of diseases. Immune dysfunction caused by dysbiosis triggers and sustains chronic inflammation. This review aims to provide a critical summary of the literature findings related to the hypothesis of a reciprocal relation between the microbiome and the immune system. Available data from studies reveal the pivotal role of the microbiome in RA pathogenesis.
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Affiliation(s)
- Plamena Ermencheva
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 13 Urvich Str., 1612 Sofia, Bulgaria; (P.E.); (G.K.); (R.S.); (S.M.)
| | - Georgi Kotov
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 13 Urvich Str., 1612 Sofia, Bulgaria; (P.E.); (G.K.); (R.S.); (S.M.)
| | - Russka Shumnalieva
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 13 Urvich Str., 1612 Sofia, Bulgaria; (P.E.); (G.K.); (R.S.); (S.M.)
- Department of Rheumatology, Medical University of Sofia, 13 Urvich Str., 1612 Sofia, Bulgaria
- Medical Faculty, Sofia University St. Kliment Ohridski, Kozyak 1, 1407 Sofia, Bulgaria
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Kozyak 1, 1407 Sofia, Bulgaria
| | - Simeon Monov
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 13 Urvich Str., 1612 Sofia, Bulgaria; (P.E.); (G.K.); (R.S.); (S.M.)
- Department of Rheumatology, Medical University of Sofia, 13 Urvich Str., 1612 Sofia, Bulgaria
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6
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Li Y, Wang W, Zhou D, Li L. The causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional Mendelian randomization study. Front Med (Lausanne) 2024; 11:1403851. [PMID: 38966529 PMCID: PMC11222563 DOI: 10.3389/fmed.2024.1403851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 06/11/2024] [Indexed: 07/06/2024] Open
Abstract
Background Several observational studies suggested an association between rheumatoid arthritis (RA) and bronchiectasis. Nevertheless, the presence of a causal relationship between these conditions is yet to be determined. This study aimed to investigate whether genetically predicted RA is associated with the risk of bronchiectasis and vice versa. Methods We obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings. Results In the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10-1.27; p = 2.34 × 10-6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations. Conclusion This study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.
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Affiliation(s)
- Yuanyuan Li
- Department of Respiratory and Critical Care Medicine, Wuhan Fourth Hospital, Wuhan, Hubei, China
| | - Weina Wang
- Department of Respiratory and Critical Care Medicine, Wuhan Fourth Hospital, Wuhan, Hubei, China
| | - Dengfeng Zhou
- Department of Respiratory and Critical Care Medicine, Wuhan Fourth Hospital, Wuhan, Hubei, China
| | - Lili Li
- Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan, Hubei, China
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7
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Mulcaire-Jones E, Pugashetti JV, Oldham JM, Khanna D. Novel Therapeutic Approaches in Connective Tissue Disease-Associated Interstitial Lung Disease. Semin Respir Crit Care Med 2024; 45:435-448. [PMID: 38740369 PMCID: PMC11875204 DOI: 10.1055/s-0044-1786155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Connective tissue diseases (CTD) comprise a group of autoimmune diseases that can affect multiple organs in the body including the lungs. The most common form of pulmonary involvement is interstitial lung disease (ILD). CTD-associated ILD (CTD-ILD) can take one of several courses including nonprogressive, chronically progressive, or rapidly progressive. Chronically and rapidly progressive patterns are associated with increased mortality. Limited randomized controlled trial data are available for treatment of CTD-ILD, with most data coming from systemic sclerosis-related ILD. The current first-line treatment for all CTD-ILD is immunosuppression with consideration of antifibrotics, stem cell transplant, and lung transplant in progressive disease. In this article, we review data for ILD treatment options in systemic sclerosis, rheumatoid arthritis, myositis, and primary Sjögren's syndrome-related ILDs.
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Affiliation(s)
- Erica Mulcaire-Jones
- Division of Rheumatology, Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Janelle Vu Pugashetti
- Division of Pulmonary and Critical Care Medicine, Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Justin M. Oldham
- Division of Pulmonary and Critical Care Medicine, Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Dinesh Khanna
- Division of Rheumatology, Internal Medicine, University of Michigan, Ann Arbor, Michigan
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8
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Vu Pugashetti J, Lee JS. Overview of Rheumatoid Arthritis-Associated Interstitial Lung Disease and Its Treatment. Semin Respir Crit Care Med 2024; 45:329-341. [PMID: 38484788 PMCID: PMC11483238 DOI: 10.1055/s-0044-1782218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2024]
Abstract
Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indicators are largely byproducts of prior ILD progression, including low or decreasing forced vital capacity and extensive or worsening fibrosis on imaging. In the absence of validated tools to predict treatment response, decisions about whether to initiate or augment treatment are instead based on clinical judgment. In general, treatment should be initiated in patients who are symptomatic, progressing, or at high risk of poor outcomes. Retrospective data suggest that mycophenolate mofetil, azathioprine, and rituximab are likely effective therapies for RA-ILD. Abatacept is also emerging as a potential first-line treatment option for patients with RA-ILD. Further, recent data demonstrate that immunosuppression may be beneficial even in patients with a usual interstitial pneumonia (UIP) pattern on imaging, suggesting that immunosuppression should be considered irrespective of imaging pattern. Recent randomized controlled trials have shown that antifibrotic medications, such as nintedanib and likely pirfenidone, slow forced vital capacity decline in RA-ILD. Consideration can be given to antifibrotic initiation in patients progressing despite immunosuppression, particularly in patients with a UIP pattern. Future research directions include developing tools to predict which patients will remain stable from patients who will progress, discriminating patients who will respond to treatment from nonresponders, and developing algorithms for starting immunosuppression, antifibrotics, or both as first-line therapies.
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Affiliation(s)
- Janelle Vu Pugashetti
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan
| | - Joyce S. Lee
- Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Mukhatayev Z, Adilbayeva A, Kunz J. CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis. Cells 2024; 13:946. [PMID: 38891078 PMCID: PMC11171484 DOI: 10.3390/cells13110946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/13/2024] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.
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Affiliation(s)
| | | | - Jeannette Kunz
- Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khans St., 020000 Astana, Kazakhstan; (Z.M.); (A.A.)
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10
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Al-Baldawi S, Zúñiga Salazar G, Zúñiga D, Balasubramanian S, Mehmood KT. Interstitial Lung Disease in Rheumatoid Arthritis: A Review. Cureus 2024; 16:e53632. [PMID: 38449991 PMCID: PMC10917126 DOI: 10.7759/cureus.53632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2024] [Indexed: 03/08/2024] Open
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Although the joints are typically the first area affected in RA, it can also involve extra-articular regions. This article provides an overview on rheumatoid arthritis-associated interstitial lung disease (RA-ILD), a component of the disease manifestations leading to significant morbidity and mortality. Managing these pulmonary symptoms in people with RA poses a number of difficulties for medical professionals. In this review article, we shed light on the prevalence of RA-ILD and the common pulmonary manifestations of RA, while focusing on the evolving pathogenesis concepts that link them to RA's autoimmune cascade. We also address the diagnostic challenges and the available screening modalities that aid in the early recognition and effective management of these pulmonary complications. Furthermore, glucocorticoids, disease-modifying antirheumatic medications, immunosuppressive medications, and biological agents are among the pharmacological approaches that have been explored in this review study.
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Affiliation(s)
- Shahad Al-Baldawi
- Department of Rheumatology, Al-Yarmouk Teaching Hospital, Baghdad, IRQ
| | | | - Diego Zúñiga
- Department of Medicine, Universidad Católica de Santiago de Guayaquil, Guayaquil, ECU
| | | | - Khawar Tariq Mehmood
- Department of Internal Medicine, Aster Hospital Br of Aster Dm Healthcare FZC, Dubai, ARE
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Lee KS, Han J, Wada N, Hata A, Lee HY, Yi C, Hino T, Doyle TJ, Franquet T, Hatabu H. Imaging of Pulmonary Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis. AJR Am J Roentgenol 2024; 222:e2329119. [PMID: 37095673 DOI: 10.2214/ajr.23.29119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
Pulmonary fibrosis is recognized as occurring in association with a wide and increasing array of conditions, and it presents with a spectrum of chest CT appearances. Idiopathic pulmonary fibrosis (IPF), which corresponds histologically with usual interstitial pneumonia and represents the most common idiopathic interstitial pneumonia, is a chronic progressive fibrotic interstitial lung disease (ILD) of unknown cause. Progressive pulmonary fibrosis (PPF) describes the radiologic development of pulmonary fibrosis in patients with ILD of a known or unknown cause other than IPF. The recognition of PPF impacts management of patients with ILD-for example, in guiding initiation of antifibrotic therapy. Interstitial lung abnormalities are an incidental CT finding in patients without suspected ILD and may represent an early intervenable form of pulmonary fibrosis. Traction bronchiectasis and/or bronchiolectasis, when detected in the setting of chronic fibrosis, is generally considered evidence of irreversible disease, and progression predicts worsening mortality risk. Awareness of the association between pulmonary fibrosis and connective tissue diseases, particularly rheumatoid arthritis, is increasing. This review provides an update on the imaging of pulmonary fibrosis, with attention given to recent advances in disease understanding with relevance to radiologic practice. The essential role of a multidisciplinary approach to clinical and radiologic data is highlighted.
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Affiliation(s)
- Kyung Soo Lee
- Department of Radiology, Samsung ChangWon Hospital, Sungkyunkwan University School of Medicine, ChangWon, Republic of Korea
| | - Joungho Han
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Noriaki Wada
- Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115
| | - Akinori Hata
- Department of Radiology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Ho Yun Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - ChinA Yi
- Department of Radiology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Takuya Hino
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tracy J Doyle
- Pulmonary and Critical Care Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Tomas Franquet
- Department of Diagnostic Radiology, Hospital de Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - Hiroto Hatabu
- Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115
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Kim Y, Yang HI, Kim KS. Etiology and Pathogenesis of Rheumatoid Arthritis-Interstitial Lung Disease. Int J Mol Sci 2023; 24:14509. [PMID: 37833957 PMCID: PMC10572849 DOI: 10.3390/ijms241914509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 09/19/2023] [Accepted: 09/23/2023] [Indexed: 10/15/2023] Open
Abstract
Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast-myofibroblast transition, epithelial-mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.
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Affiliation(s)
- Yerin Kim
- Department of Medicine, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea;
| | - Hyung-In Yang
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea;
| | - Kyoung-Soo Kim
- East-West Bone & Joint Disease Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea
- Department of Clinical Pharmacology and Therapeutics, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea
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Cheng WC, Chang SH, Chen WC, Wu BR, Chen CH, Lin CC, Hsu WH, Lan JL, Chen DY. Application of impulse oscillometry to detect interstitial lung disease and airway disease in adults with rheumatoid arthritis. BMC Pulm Med 2023; 23:331. [PMID: 37684581 PMCID: PMC10485984 DOI: 10.1186/s12890-023-02615-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 08/27/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.
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Affiliation(s)
- Wen-Chien Cheng
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Shih-Hsin Chang
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan.
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.
| | - Wei-Chun Chen
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Bing-Ru Wu
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Chia-Hung Chen
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chi-Chien Lin
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan
- and Animal Biotechnology Center, Institute of Biomedical Science, the iEGG , National Chung-Hsing University, Taichung, Taiwan
| | - Wu-Huei Hsu
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Joung-Liang Lan
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan
| | - Der-Yuan Chen
- Department of Life Science, National Chung Hsing University, Taichung, Taiwan.
- College of Medicine, China Medical University, Taichung, Taiwan.
- College of Medicine, National Chung Hsing University, Taichung, Taiwan.
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Triggianese P, Conigliaro P, De Martino E, Monosi B, Chimenti MS. Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease. Open Access Rheumatol 2023; 15:65-79. [PMID: 37214353 PMCID: PMC10198272 DOI: 10.2147/oarrr.s318826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 05/05/2023] [Indexed: 05/24/2023] Open
Abstract
Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of self-tolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases.
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Affiliation(s)
- Paola Triggianese
- Department of Systems Medicine, Rheumatology, Allergology and Clinical Immunology, University of Rome Tor Vergata, Rome, Italy
| | - Paola Conigliaro
- Department of Systems Medicine, Rheumatology, Allergology and Clinical Immunology, University of Rome Tor Vergata, Rome, Italy
| | - Erica De Martino
- Department of Systems Medicine, Rheumatology, Allergology and Clinical Immunology, University of Rome Tor Vergata, Rome, Italy
| | - Benedetta Monosi
- Department of Systems Medicine, Rheumatology, Allergology and Clinical Immunology, University of Rome Tor Vergata, Rome, Italy
| | - Maria Sole Chimenti
- Department of Systems Medicine, Rheumatology, Allergology and Clinical Immunology, University of Rome Tor Vergata, Rome, Italy
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15
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Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study. THE LANCET. RESPIRATORY MEDICINE 2023; 11:87-96. [PMID: 36075242 DOI: 10.1016/s2213-2600(22)00260-0] [Citation(s) in RCA: 92] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/21/2022] [Accepted: 06/22/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18-85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871. FINDINGS From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group; OR 0·67 [95% CI 0·22 to 2·03]; p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (-66 vs -146; p=0·0082) and FVC% (-1·02 vs -3·21; p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group; OR 0·52 [95% CI 0·14-1·90]; p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group; OR 0·68 [0·30-1·54]; p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths. INTERPRETATION Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. FUNDING Genentech.
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16
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Predictors of long-term prognosis in rheumatoid arthritis-related interstitial lung disease. Sci Rep 2022; 12:9469. [PMID: 35676424 PMCID: PMC9177673 DOI: 10.1038/s41598-022-13474-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 05/09/2022] [Indexed: 11/08/2022] Open
Abstract
The aim of the study was to identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease (RA-ILD). 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on changes in Quantitative Modified HRCT scores and PFTs over time. Specific serum protein biomarkers were assessed in serum samples at baseline and Year 5 by Multiplex enzyme-linked immunosorbent assays (ELISAs). At Year 5, 32% of patients demonstrated progressive RA-ILD, 35% were stable, and 33% improved. Baseline age and rheumatoid factor (RF) were significantly different between RA-ILD outcomes of progression vs. no-progression (p < 0.05). Changes in levels of CXCL11/I-TAC and MMP13 over 5 years also distinguished pulmonary outcomes (p < 0.05). A final binary logistic regression model revealed that baseline age and changes in serum MMP13 as well as CXCL11/I-TAC were associated with RA-ILD progression at Year 5 (p < 0.01), with an AUC of 0.7772. Collectively, these analyses demonstrated that baseline clinical variables (age, RF) and shifts in levels of selected serum proteins (CXCL11/I-TAC, MMP13) were strongly linked to RA-ILD outcome over time.
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17
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Laria A, Lurati AM, Zizzo G, Zaccara E, Mazzocchi D, Re KA, Marrazza M, Faggioli P, Mazzone A. Interstitial Lung Disease in Rheumatoid Arthritis: A Practical Review. Front Med (Lausanne) 2022; 9:837133. [PMID: 35646974 PMCID: PMC9136053 DOI: 10.3389/fmed.2022.837133] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/07/2022] [Indexed: 11/25/2022] Open
Abstract
Rheumatoid arthritis (RA) is a systemic inflammatory disease, which primarily causes symmetric polyarthritis. An extrarticolar involvement is common, and the commonly involved organ is lungs. Although cardiac disease is responsible for most RA-related deaths, pulmonary disease is also a major contributor, accounting for ~10-20% of all mortality. Pulmonary disease is a common (60-80% of patients with RA) extra-articular complication of RA. Optimal screening, diagnostic, and treatment strategies of pulmonary disease remain uncertain, which have been the focus of an ongoing investigation. Clinicians should regularly assess patients with RA for the signs and symptoms of pulmonary disease and, reciprocally, consider RA and other connective tissue diseases when evaluating a patient with pulmonary disease of an unknown etiology. RA directly affects all anatomic compartments of the thorax, including the lung parenchyma, large and small airways, pleura, and less commonly vessels. In addition, pulmonary infection and drug-induced lung disease associated with immunosuppressive agents used for the treatment of RA may occur.
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Affiliation(s)
- Antonella Laria
- Asst Ovest Milanese–Rheumatology Unit, Magenta Hospital, Milan, Italy
| | | | - Gaetano Zizzo
- Asst Ovest Milanese–Internal Medicine Department, Cuggiono Hospital, Milan, Italy
| | - Eleonora Zaccara
- Asst Ovest Milanese–Internal Medicine Unit, Legnano Hospital, Milan, Italy
| | - Daniela Mazzocchi
- Asst Ovest Milanese–Rheumatology Unit, Magenta Hospital, Milan, Italy
| | - Katia Angela Re
- Asst Ovest Milanese–Rheumatology Unit, Magenta Hospital, Milan, Italy
| | | | - Paola Faggioli
- Asst Ovest Milanese–Internal Medicine Unit, Legnano Hospital, Milan, Italy
| | - Antonino Mazzone
- Asst Ovest Milanese–Internal Medicine Unit, Legnano Hospital, Milan, Italy
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18
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Matson SM, Deane KD, Peljto AL, Bang TJ, Sachs PB, Walts AD, Collora C, Ye S, Demoruelle MK, Humphries SM, Schwartz DA, Lee JS. Prospective Identification of Subclinical Interstitial Lung Disease in a Rheumatoid Arthritis Cohort Is Associated with the MUC5B Promoter Variant. Am J Respir Crit Care Med 2022; 205:473-476. [PMID: 34874815 PMCID: PMC8886943 DOI: 10.1164/rccm.202109-2087le] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Affiliation(s)
| | - Kevin D. Deane
- University of Colorado School of MedicineAurora, Colorado
| | - Anna L. Peljto
- University of Colorado School of MedicineAurora, Colorado
| | - Tami J. Bang
- University of Colorado School of MedicineAurora, Colorado
| | - Peter B. Sachs
- University of Colorado School of MedicineAurora, Colorado
| | - Avram D. Walts
- University of Colorado School of MedicineAurora, Colorado
| | | | - Shuyu Ye
- University of Colorado School of MedicineAurora, Colorado
| | | | | | | | - Joyce S. Lee
- University of Colorado School of MedicineAurora, Colorado
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19
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El Ouali I, Habib Chorfa S, El Hamzaoui H, Alilou M, Jroundi L, Laamrani FZ. Pulmonary air leak syndrome in rheumatoid arthritis patient. SAGE Open Med Case Rep 2022; 10:2050313X221125361. [PMID: 36147592 PMCID: PMC9486260 DOI: 10.1177/2050313x221125361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 08/24/2022] [Indexed: 11/18/2022] Open
Abstract
Pulmonary air leak syndromes involve dissection of air out of the normal pulmonary
airspaces and include pulmonary interstitial emphysema, pneumothorax, pneumomediastinum,
pneumopericardium, pneumoperitoneum, subcutaneous emphysema and systemic air embolism. It
presents as a spontaneous extension of dissecting air without a history of a procedure or
penetrating injury. Pulmonary air leak syndromes are extremely rare complications of
systemic autoimmune connective tissue diseases. Few cases were reported in the literature
regarding rheumatoid arthritis patients. The purpose of this article is to emphasize on
this rare pulmonary complication and discuss the physiopathology of the disease and the
different risk factors for a better management of these patients. We report the case of a
45-year-old female, with a history of proven rheumatoid arthritis under methotrexate and
steroids, who presented with a spontaneous dissecting subcutaneous emphysema,
pneumothorax, pneumomediastinum and pneumoperitoneum. The patient’s condition improved
after chest drainage and adjustment of her medical treatment.
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Affiliation(s)
- Ibtissam El Ouali
- Emergency Radiology Department, IBN SINA Hospital Center, Rabat, Morocco
| | - Sara Habib Chorfa
- Emergency Radiology Department, IBN SINA Hospital Center, Rabat, Morocco
| | | | - Mustapha Alilou
- Emergency Department, IBN SINA Hospital Center, Rabat, Morocco
| | - Laila Jroundi
- Emergency Radiology Department, IBN SINA Hospital Center, Rabat, Morocco
| | - FZ Laamrani
- Emergency Radiology Department, IBN SINA Hospital Center, Rabat, Morocco
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20
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Franquet T, Franks TJ, Galvin JR, Marchiori E, Giménez A, Mazzini S, Johkoh T, Lee KS. Non-Infectious Granulomatous Lung Disease: Imaging Findings with Pathologic Correlation. Korean J Radiol 2021; 22:1416-1435. [PMID: 34132073 PMCID: PMC8316771 DOI: 10.3348/kjr.2020.1082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/26/2020] [Accepted: 11/01/2020] [Indexed: 12/14/2022] Open
Abstract
Non-infectious granulomatous lung disease represents a diverse group of disorders characterized by pulmonary opacities associated with granulomatous inflammation, a relatively nonspecific finding commonly encountered by pathologists. Some lesions may present a diagnostic challenge because of nonspecific imaging features; however, recognition of the various imaging manifestations of these disorders in conjunction with patients' clinical history, such as age, symptom onset and duration, immune status, and presence of asthma or cutaneous lesions, is imperative for narrowing the differential diagnosis and determining appropriate management of this rare group of disorders. In this pictorial review, we describe the pathologic findings of various non-infectious granulomatous lung diseases as well as the radiologic features and high-resolution computed tomography imaging features.
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Affiliation(s)
- Tomás Franquet
- Department of Diagnostic Radiology, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain.
| | - Teri J Franks
- Department of Defense, Pulmonary & Mediastinal Pathology, The Joint Pathology Center, Silver Spring, MD, USA
| | - Jeffrey R Galvin
- Department of Diagnostic Radiology, Chest Imaging, & Pulmonary Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Edson Marchiori
- Department of Radiology, Hospital Universitário Clementino Fraga Filho-Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Ana Giménez
- Department of Diagnostic Radiology, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Sandra Mazzini
- Department of Diagnostic Radiology, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Takeshi Johkoh
- Department of Radiology, Kansai Rosai Hospital, Hyogo, Japan
| | - Kyung Soo Lee
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, Korea
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21
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McDermott GC, Doyle TJ, Sparks JA. Interstitial lung disease throughout the rheumatoid arthritis disease course. Curr Opin Rheumatol 2021; 33:284-291. [PMID: 33625044 PMCID: PMC8268047 DOI: 10.1097/bor.0000000000000787] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW To summarize the current understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) throughout the rheumatoid arthritis (RA) disease course from preclinical to established disease. RECENT FINDINGS ILD is a serious extra-articular manifestation of RA. Multiple studies have demonstrated a high prevalence of both subclinical and clinical ILD throughout the RA disease course. Investigations of patients without RA have demonstrated an association between RA-related autoantibodies like anticitrullinated protein antibodies (ACPA) and interstitial abnormalities on lung imaging. A significant proportion of RA-ILD patients develop ILD prior to articular manifestations, suggesting that the lung plays a central role in RA development, perhaps through ACPA production. RA-ILD also occurs in early RA, when exuberant autoantibody production and systemic inflammation may propagate pulmonary disease activity. In patients with established RA, a high burden of subclinical and clinical ILD results in significant morbidity, mortality, and healthcare expenditure. Multiple epidemiologic and genetic risk factors, as well as serum biomarkers, have been associated with RA-ILD. SUMMARY Subclinical and clinical ILD occur frequently in preclinical, early, and established RA and may play a key role in RA-related autoantibody production and disease progression. Further studies are needed to better understand the risk factors, prognosis, and potential therapies for RA-ILD.
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Affiliation(s)
- Gregory C. McDermott
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Tracy J. Doyle
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Jeffrey A. Sparks
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Boston, MA
- Harvard Medical School, Boston, MA
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22
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Kim H, Sung YK. Epidemiology of Rheumatoid Arthritis in Korea. JOURNAL OF RHEUMATIC DISEASES 2021; 28:60-67. [PMID: 37476013 PMCID: PMC10324889 DOI: 10.4078/jrd.2021.28.2.60] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 03/18/2021] [Indexed: 07/22/2023]
Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterised by symmetrical involvement of the joints, associated extra-articular manifestations and functional disability. In Korea, several epidemiologic studies reporting prevalence and incidence rates of RA have been conducted using large databases such as claims databases, national surveys, prospective cohort databases or electronic health records; according to these data sources, the estimated prevalence ranged from 0.27% to 1.85%. The prevalence of extra-articular manifestations such as interstitial lung disease (ILD) and Sjögren's syndrome (SS) were also reported, but an issue of external validity of the study results persisted. In this review, we detail the epidemiology of Korean RA patients, focusing on the prevalence of RA and the frequency of systemic extra-articular manifestations including ILD and SS reported in previous studies. In addition, we discuss the current methodological issues which are inherent in Korean epidemiologic studies for patients with RA with understanding of the characteristics of each database.
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Affiliation(s)
- Hyoungyoung Kim
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Yoon-Kyoung Sung
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
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23
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Hussein MS, El-Barbary AM, Nada DW, Gaber RA, Elkolaly RM, Aboelhawa MA. Identification of serum interleukin-13 and interleukin-13 receptor subunit expressions: Rheumatoid arthritis-associated interstitial lung disease. Int J Rheum Dis 2021; 24:591-598. [PMID: 33638296 DOI: 10.1111/1756-185x.14084] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/28/2020] [Accepted: 01/27/2021] [Indexed: 01/08/2023]
Abstract
AIM OF THE WORK To identify the role of serum IL-13, and its receptor subunit expressions as a serologic marker of rheumatoid arthritis (RA)-associated ILD (RA-ILD). PATIENTS AND METHODS Fifty RA patients with ILD and 50 RA patients without ILD were examined, in addition to 50 controls. Disease Activity Score in 28 joints (DAS-28), the Health Assessment Questionnaire (HAQ), and medication history were evaluated. ESR, CRP, RF, Anti-CCP, Serum Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D) levels, Interleukin 13 and its receptors (IL-13 Rα1 and L-13 Rα2), and mRNA relative expression levels in peripheral blood mononuclear cells (PBMCs) were measured. High-resolution computed tomography (HRCT) scores were used with all RA patients with interstitial lung disease. RESULTS Mean age, percent of male affection, duration of the disease, DAS28 and MHAQ were significantly higher in the RA-ILD group than in the RA-no ILD group. ESR, CRP, RF, anti-CCP, serum KL-6, SP-D, IL-13 levels, IL-13 Rα1and IL-13 Rα2 mRNA expressions were significantly increased in RA patients compared to controls; in addition, their levels were significantly higher in the RA-ILD group than in the RA-no ILD group. Serum IL-13 levels and IL-13 Rα1and IL-13 Rα2 were positively correlated with RF, Anti-CCP, KL-6, SP-D, and the HRCT score (P < .001). CONCLUSIONS Serum IL-13 and its receptor subunit expressions are useful biomarkers which can be used in detecting severity of the interstitial lung disease in RA patients.
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Kawano-Dourado L, Doyle TJ, Bonfiglioli K, Sawamura MVY, Nakagawa RH, Arimura FE, Lee HJ, Rangel DADS, Bueno C, Carvalho CRR, Sabbag ML, Molina C, Rosas IO, Kairalla RA. Baseline Characteristics and Progression of a Spectrum of Interstitial Lung Abnormalities and Disease in Rheumatoid Arthritis. Chest 2020; 158:1546-1554. [PMID: 32428513 DOI: 10.1016/j.chest.2020.04.061] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 02/08/2020] [Accepted: 04/23/2020] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Interstitial lung abnormalities (ILA) and interstitial lung disease (ILD) are seen in up to 60% of individuals with rheumatoid arthritis (RA), some of which will progress to have a significant impact on morbidity and mortality rates. Better characterization of progressive interstitial changes and identification of risk factors that are associated with progression may enable earlier intervention and improved outcomes. RESEARCH QUESTION What are baseline characteristics associated with RA-ILD progression? STUDY DESIGN AND METHODS We performed a retrospective study in which all clinically indicated CT chest scans in adult individuals with RA from 2014 to 2016 were evaluated for interstitial changes, and the data were further subdivided into ILA and ILD based on clinical record review. Progression was determined visually and subsequently semiquantified. RESULTS Those individuals with a spectrum of interstitial changes (64 of 293) were older male smokers and less likely to be receiving biologics/small molecule disease-modifying antirheumatic drugs. Of 44% of the individuals with ILA, 46% had had chest CT scans performed for nonpulmonary indications. Of the 56 individuals with ILA/ILD with sequential CT scans, 38% had evidence of radiologic progression over 4.4 years; 29% of of individuals with ILA progressed. Risk factors for progressive ILA/ILD included a subpleural distribution and higher baseline involvement. INTERPRETATION Of 293 individuals with RA with clinically indicated CT scans, interstitial changes were observed in 22%, one-half of whom had had a respiratory complaint at the time of imaging; radiologic progression was seen in 38%. Of individuals with progressive ILA, one-half had had baseline CT scans performed for nonpulmonary indications. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with progression. Prospective longitudinal studies of RA-ILA are necessary.
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Affiliation(s)
- Leticia Kawano-Dourado
- Pulmonary Division, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil; Research Institute, Hospital do Coração (HCor), São Paulo, Brazil.
| | - Tracy J Doyle
- Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Karina Bonfiglioli
- Heart Institute (InCor), the Division of Rheumatology, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
| | - Márcio V Y Sawamura
- Division of Radiology, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
| | | | - Fábio E Arimura
- Pulmonary Division, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
| | - Hye J Lee
- Division of Radiology, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
| | | | - Cleonice Bueno
- Division of Radiology, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
| | - Carlos R R Carvalho
- Pulmonary Division, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
| | | | - Camila Molina
- Centro Universitário São Camilo-São Paulo, São Paulo, Brazil
| | - Ivan O Rosas
- Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Ronaldo A Kairalla
- Pulmonary Division, Hospital das Clinicas HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
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25
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Duarte AC, Porter JC, Leandro MJ. The lung in a cohort of rheumatoid arthritis patients-an overview of different types of involvement and treatment. Rheumatology (Oxford) 2020; 58:2031-2038. [PMID: 31089697 DOI: 10.1093/rheumatology/kez177] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 04/04/2019] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES Lung involvement in RA has several manifestations and is a major cause of morbidity and mortality. The aim of this study was to characterize the different types of lung disease and response to treatment in a UK cohort of RA patients. METHODS RA patients who had undergone high resolution CT scans of the lung were identified and scans reviewed. Demographic data, RA features, complementary exams and treatments were recorded for those with radiological evidence of lung involvement. Descriptive analysis was performed, and Mann-Whitney U and χ2 tests were used for comparison between different radiological subtypes. RESULTS Lung disease was reported in 87 (7.7%) of 1129 RA patients, usually (97.7%) post-dating articular symptoms. Most patients had positive RF (74/84; 88.1%) and ACPA (72/82; 87.7%). Interstitial lung disease (ILD) was the most common pattern, reported in 45 (51.7%) patients. Drug-induced lung disease was reported in 2 of 64 (3.1%) patients treated with MTX. Rituximab was used in 26 (57.8%) patients with ILD, with evidence of disease improvement or stabilization in patients with non-specific interstitial pneumonia and organizing pneumonia. During lung disease follow-up (6.7 ± 4.1 years), 22 (25.3%) patients were admitted to hospital with respiratory infections, with 14 (63.6%) of them having underlying bronchiectasis. Lung disease-related mortality was estimated at 8%. CONCLUSION ILD was the most prevalent manifestation of lung involvement in RA and was associated with higher mortality. Immunosuppressive drugs used in RA were rarely associated with lung toxicity, and rituximab demonstrated promising results for the treatment of RA-ILD.
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Affiliation(s)
- Ana C Duarte
- Rheumatology Department, Hospital Garcia de Orta, Almada, Portugal
| | - Joanna C Porter
- UCL Respiratory, London, UK.,Center for Interstitial Lung Disease, London, UK
| | - Maria J Leandro
- Center for Rheumatology, University College London Hospitals NHS Foundation Trust, London, UK
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26
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Kass DJ, Nouraie M, Glassberg MK, Ramreddy N, Fernandez K, Harlow L, Zhang Y, Chen J, Kerr GS, Reimold AM, England BR, Mikuls TR, Gibson KF, Dellaripa PF, Rosas IO, Oddis CV, Ascherman DP. Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis. Arthritis Rheumatol 2020; 72:409-419. [PMID: 31532072 DOI: 10.1002/art.41123] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 09/12/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA), occurring in up to 40% of patients during the course of their disease. Early diagnosis is critical, particularly given the shared clinicoepidemiologic features between advanced rheumatoid arthritis-associated ILD (RA-ILD) and idiopathic pulmonary fibrosis (IPF). This study was undertaken to define the molecular basis of this overlap through comparative profiling of serum proteins in RA-ILD and IPF. METHODS Multiplex enzyme-linked immunosorbent assays (ELISAs) were used to profile 45 protein biomarkers encompassing cytokines/chemokines, growth factors, and matrix metalloproteinases (MMPs) in sera obtained from RA patients with ILD and those without, individuals with IPF, and healthy controls. Levels of selected serum proteins were compared between patient subgroups using adjusted linear regression, principal component analysis (PCA), and least absolute shrinkage and selection operator (LASSO) modeling. RESULTS Multiplex ELISA-based assessment of sera from 2 independent cohorts (Veterans Affairs [VA] and Non-VA) revealed a number of non-overlapping biomarkers distinguishing RA-ILD from RA without ILD (RA-no ILD) in adjusted regression models. Parallel analysis of sera from IPF patients also yielded a discriminatory panel of protein markers in models adjusted for age/sex/smoking, which showed differential overlap with profiles linked to RA-ILD in the VA cohort versus the Non-VA cohort. PCA revealed several distinct functional groups of RA-ILD-associated markers that, in the VA cohort, encompassed proinflammatory cytokines/chemokines as well as 2 different subsets of MMPs. Finally, LASSO regression modeling in the Non-VA and VA cohorts revealed distinct biomarker combinations capable of discriminating RA-ILD from RA-no ILD. CONCLUSION Comparative serum protein biomarker profiling represents a viable method for distinguishing RA-ILD from RA-no ILD and identifying population-specific mediators shared with IPF.
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Affiliation(s)
- Daniel J Kass
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Mehdi Nouraie
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Nitya Ramreddy
- University of Miami Miller School of Medicine, Miami, Florida
| | - Karen Fernandez
- University of Miami Miller School of Medicine, Miami, Florida
| | - Lisa Harlow
- University of Miami Miller School of Medicine, Miami, Florida
| | - Yingze Zhang
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Jean Chen
- First Xiamen University, Xiamen, China
| | | | | | - Bryant R England
- VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha
| | - Ted R Mikuls
- VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha
| | - Kevin F Gibson
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Ivan O Rosas
- Brigham and Women's Hospital, Boston, Massachusetts
| | - Chester V Oddis
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Dana P Ascherman
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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27
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Duarte AC, Porter J, Leandro MJ. Bronchiectasis in rheumatoid arthritis. A clinical appraisial. Joint Bone Spine 2020; 87:419-424. [PMID: 32007647 DOI: 10.1016/j.jbspin.2019.12.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/20/2019] [Indexed: 10/25/2022]
Abstract
Bronchiectasis is defined as irreversibly damaged and dilated bronchi and is one of the most common pulmonary manifestations in patients with rheumatoid arthritis (RA). The model of RA-associated autoimmunity induced in some individuals by chronic bacterial infection in bronchiectasis is becoming increasingly acceptable, although a genetic predisposition to RA-associated bronchiectasis has also been demonstrated. Bronchiectasis should be suspected in RA patients with chronic cough and sputum production or frequent respiratory infections and the diagnosis must be confirmed by thoracic high-resolution computed tomography. Management of patients with RA-associated bronchiectasis includes a multimodal treatment approach. Similar to all patients with non-cystic fibrosis bronchiectasis, patients with RA-associated bronchiectasis benefit from a pulmonary rehabilitation program, including an exercise/muscle strengthening program and an education program with a specific session on airway clearance techniques. Prophylactic antibiotics are recommended for patients with frequent (3 or more infective exacerbations per year) or severe infections requiring hospitalization/intravenous antibiotics and inhaled corticosteroids and long-acting β2-agonists should be used in patients with non-cystic fibrosis bronchiectasis and associated airway hyper-responsiveness. In patients with RA-associated bronchiectasis the use of immunomodulatory drugs has to be carefully considered, as they are essential to control disease activity, despite being associated with an increased infectious risk. Pneumococcal and influenza vaccines are advised to all patients with RA-associated bronchiectasis in order to reduce the risk of infection. Patients with RA-associated bronchiectasis have a poorer prognosis than those with either RA or bronchiectasis alone and require regular follow-up, under the joint care of a rheumatologist and a pulmonologist.
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Affiliation(s)
- Ana Catarina Duarte
- Rheumatology department, Hospital Garcia de Orta EPE, Avenida Torrado da Silva, 2805-267 Almada, Portugal.
| | - Joanna Porter
- UCL Respiratory, University College London Hospitals NHS Foundation Trust, 235, Euston Road, Bloomsbury, NW1 2BU London, United Kingdom; Center for Interstitial Lung Disease, University College London Hospitals NHS Foundation Trust, 235, Euston Road, Bloomsbury, NW1 2BU London, United Kingdom
| | - Maria José Leandro
- Center for Rheumatology, University College London Hospitals NHS Foundation Trust, 235, Euston Road, Bloomsbury, NW1 2BU London, United Kingdom
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Solomon JJ, Danoff SK, Goldberg HJ, Woodhead F, Kolb M, Chambers DC, DiFranco D, Spino C, Haynes-Harp S, Hurwitz S, Peters EB, Dellaripa PF, Rosas IO. The Design and Rationale of the Trail1 Trial: A Randomized Double-Blind Phase 2 Clinical Trial of Pirfenidone in Rheumatoid Arthritis-Associated Interstitial Lung Disease. Adv Ther 2019; 36:3279-3287. [PMID: 31515704 DOI: 10.1007/s12325-019-01086-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is the most common of the connective tissue diseases (CTD), affecting up to 0.75% of the United States (U.S.) population with an increasing prevalence. Interstitial lung disease is prevalent and morbid condition in RA (RA-ILD), affecting up to 60% of patients with RA, leading to premature death in 10% and accruing an average of US$170,000 in healthcare costs per patient over a 5-year period. Although there have been significant advances in the management of this joint disease, there are no ongoing randomized clinical trials looking at pharmacologic treatments for RA-ILD, and there currently are no U.S. Food and Drug Administration-approved drugs for RA-ILD. METHODS/DESIGN We describe the Treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) trial, a multicenter randomized, double-blind, placebo-controlled, phase 2 study of the safety, tolerability and efficacy of pirfenidone in patients with RA-ILD. The study will enroll approximately 270 subjects across a network of sites who have RA and ILD as defined by a fibrotic abnormality involving greater than 10% of the lung parenchyma. The primary endpoint of the study is the incidence of the composite endpoint of decline in percent predicted forced vital capacity of 10 or greater or death during the 52-week study period. A number of secondary and exploratory endpoints have been chosen to evaluate the safety and efficacy in different domains. DISCUSSION The TRAIL1 trial is designed to evaluate the safety and efficacy of pirfenidone in RA-ILD, a disease with significant impact on patients' quality of life and outcome. In addition to investigating the safety and efficacy of pirfenidone, this trial looks at a number of exploratory endpoints in an effort to better understand the impact of therapy on areas such as changes in quantitative high-resolution computed tomography scores and a patient's quality of life. Biospecimens will be collected in order to investigate biomarkers that could potentially predict the subtype of disease, its behavior over time, and its response to therapy. Finally, by creating a network of institutions and clinician investigators with an interest in RA-ILD, this trial will pave the way for future studies of investigational agents in an effort to reduce or eliminate the burden of disease for those suffering from RA-ILD. TRIAL FUNDING Genentech, a member of the Roche Group. TRIAL REGISTRATION Clinicaltrials.gov, identifier NCT02808871.
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Affiliation(s)
| | | | | | | | | | | | - Donna DiFranco
- School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Cathy Spino
- School of Public Health, University of Michigan, Ann Arbor, MI, USA
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29
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Fragoulis GE, Nikiphorou E, Larsen J, Korsten P, Conway R. Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment. Front Med (Lausanne) 2019; 6:238. [PMID: 31709258 PMCID: PMC6819370 DOI: 10.3389/fmed.2019.00238] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 10/10/2019] [Indexed: 12/20/2022] Open
Abstract
Rheumatoid arthritis (RA) is a type of inflammatory arthritis that affects ~1% of the general population. Although arthritis is the cardinal symptom, many extra-articular manifestations can occur. Lung involvement and particularly interstitial lung disease (ILD) is among the most common. Although ILD can occur as part of the natural history of RA (RA-ILD), pulmonary fibrosis has been also linked with methotrexate (MTX); a condition also known as MTX-pneumonitis (M-pneu). This review aims to discuss epidemiological, diagnostic, imaging and histopathological features, risk factors, and treatment options in RA-ILD and M-pneu. M-pneu, usually has an acute/subacute course characterized by cough, dyspnea and fever. Several risk factors, including genetic and environmental factors have been suggested, but none have been validated. The diagnosis is based on clinical and radiologic findings which are mostly consistent with non-specific interstitial pneumonia (NSIP), more so than bronchiolitis obliterans organizing pneumonia (BOOP). Histological findings include interstitial infiltrates by lymphocytes, histiocytes, and eosinophils with or without non-caseating granulomas. Treatment requires immediate cessation of MTX and commencement of glucocorticoids. RA-ILD shares the same symptomatology with M-pneu. However, it usually has a more chronic course. RA-ILD occurs in about 3-5% of RA patients, although this percentage is significantly increased when radiologic criteria are used. Usual interstitial pneumonia (UIP) and NSIP are the most common radiologic patterns. Several risk factors have been identified for RA-ILD including smoking, male gender, and positivity for anti-citrullinated peptide antibodies and rheumatoid factor. Diagnosis is based on clinical and radiologic findings while pulmonary function tests may demonstrate a restrictive pattern. Although no clear guidelines exist for RA-ILD treatment, glucocorticoids and conventional disease modifying antirheumatic drugs (DMARDs) like MTX or leflunomide, as well as treatment with biologic DMARDs can be effective. There is limited evidence that rituximab, abatacept, and tocilizumab are better options compared to TNF-inhibitors.
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Affiliation(s)
- George E Fragoulis
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.,Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
| | - Elena Nikiphorou
- Department of Inflammation Biology, Faculty of Life Sciences & Medicine, Centre for Rheumatic Diseases, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Jörg Larsen
- Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, Germany
| | - Peter Korsten
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Richard Conway
- Department of Rheumatology, Blackrock Clinic, Dublin, Ireland
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30
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Armstrong D, Dregan A, Ashworth M, White P, McGee C, de Lusignan S. Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in general practice. Rheumatology (Oxford) 2019; 59:1281-1287. [DOI: 10.1093/rheumatology/kez452] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 08/26/2019] [Indexed: 01/07/2023] Open
Abstract
Abstract
Objectives
To test the hypothesis that prior antibiotics influences the risk of developing RA.
Methods
A case–control study was conducted over 15 years using the UK’s Royal College of General Practitioners Research and Surveillance Centre database. The frequency and type of antibiotic prescription for patients who subsequently developed RA were compared with antibiotic prescriptions in a control group of patients who remained free of RA. Cases, defined as patients with a new diagnosis of RA made between 2006 and 2018, were matched with up to four RA-free controls on practice, age, gender and date of diagnosis. Exposure was measured by the number and type of prescriptions for antibiotics prior to the RA diagnosis or to the index date in controls.
Results
A total of 8482 patients with a new diagnosis of RA between 2006 and 2018 were compared with 22 661 controls. There was a higher likelihood of an RA diagnosis after antibiotic prescriptions within 1 year, 5 years and ever with a strong dose–response. Patients receiving >10 antibiotics in a 5 year period were more than twice as likely to receive an RA diagnosis as controls [adjusted odds ratio 2.65 (CI 2.40, 2.93)].
Conclusion
Exposure to antibiotics prior to the diagnosis was a significant risk factor for RA. This could reflect an immunological response to a compromised microbiome. Alternatively, patients with pre-symptomatic or early undiagnosed RA may have been more likely to present to their general practitioner with infections due to an unrecognized effect of RA.
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Affiliation(s)
- David Armstrong
- Department of Population Health Sciences, King’s College London
| | - Alex Dregan
- Department of Psychological Medicine, Institute of Psychiatry, Psychological, and Neurosciences, King’s College London, London
| | - Mark Ashworth
- Department of Population Health Sciences, King’s College London
| | - Patrick White
- Department of Population Health Sciences, King’s College London
| | - Chris McGee
- Department of Clinical and Experimental Medicine, Surrey University, Guildford
- Royal College of General Practitioners Research and Surveillance Centre, London, UK
| | - Simon de Lusignan
- Department of Clinical and Experimental Medicine, Surrey University, Guildford
- Royal College of General Practitioners Research and Surveillance Centre, London, UK
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31
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Elkolaly RM, Ganna SA, Nada DW, Elnaggar MH. Impulse oscillometry, an aid or a substitute? THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2019. [DOI: 10.4103/ejb.ejb_98_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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32
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Salaffi F, Carotti M, Di Carlo M, Tardella M, Giovagnoni A. High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities. Medicine (Baltimore) 2019; 98:e17088. [PMID: 31567944 PMCID: PMC6756733 DOI: 10.1097/md.0000000000017088] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
An international consensus for rheumatoid arthritis (RA) patients at risk of developing interstitial lung disease (ILD) is still lacking. The aims of study were to evaluate: the prevalence of ILD involvement in RA over high-resolution computed tomography (HRCT); the relationships between pulmonary function tests (PFTs), patient-centered measurements, and ILD; and the potential risk factors contributing to RA-ILD patients.Data regarding the clinical characteristics (age, sex, age at onset of RA), laboratory findings (rheumatoid factor [RF] and anti-citrullinated protein antibodies [ACPA]), respiratory functional assessment (forced vital capacity [FVC] and carbon monoxide diffusion capacity [DLCO]), patient-centred measures of dyspnea (PCMD), Health Assessment Questionnaire-Disability Index (HAQ-DI), and HRCT have collected retrospectively. HRCT abnormalities were evaluated using a conventional visual reader-based score (CoVR) and a computer-aided method (CaM). The relationships between the 2 HRCT scores-PFTs and PCMD-were calculated using Pearson correlation. The area under the receiving-operating characteristic (AUC-ROC) curve was calculated to determine the discriminatory performance of measurements between patients with and without ILD. The multivariate regression model was used to evaluate the association force between ILD and RA characteristics.In all, 151 patients (45 males and 106 females, mean age 53.4 ± 7.6 years) were included. ILD had been detected in 29 patients out of 151 (19.2%). Usual interstitial pneumonia was the most common HRCT. RA-ILD patients were older, and older at RA onset (both P < .01), with a higher HAQ-DI (P < .05) than patients without ILD. ACPA positivity and titer were higher in the RA-ILD group (P = .02). Extent and severity of ILD, and total CoVR and CaM score closely related to DLCO and PCMD (both P < .0001). A reduced DLCO was the most sensitive test for predicting the presence of ILD on HRCT (AUC-ROC 0.811 ± 0.037). Advanced age (P < .0001), age at RA onset (P = .025), ACPA titer (P = .004), and smoking (P = .008) were independent explanatory variables of HRCT damage in multivariate analysis.The RA-ILD is associated with age and older age of RA onset, smoking, and ACPA titer. DLCO seems to be the most sensitive parameter to predict ILD on HRCT, followed by PCMD.
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Affiliation(s)
- Fausto Salaffi
- Rheumatological Clinic, Università Politecnica delle Marche, Jesi
| | - Marina Carotti
- Radiology Department, Università Politecnica delle Marche, Ancona, Italy
| | - Marco Di Carlo
- Rheumatological Clinic, Università Politecnica delle Marche, Jesi
| | - Marika Tardella
- Rheumatological Clinic, Università Politecnica delle Marche, Jesi
| | - Andrea Giovagnoni
- Radiology Department, Università Politecnica delle Marche, Ancona, Italy
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Huang S, He X, Doyle TJ, Zaccardelli A, Marshall AA, Friedlander HM, Blaustein RB, Smith EA, Cui J, Iannaccone CK, Mahmoud TG, Weinblatt ME, Dellaripa PF, Shadick NA, Sparks JA. Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry. Clin Rheumatol 2019; 38:3401-3412. [PMID: 31410660 DOI: 10.1007/s10067-019-04733-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 07/11/2019] [Accepted: 07/31/2019] [Indexed: 11/26/2022]
Abstract
INTRODUCTION We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs). METHODS We studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95% CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics. RESULTS Among 1272 analyzed subjects, mean age was 56.3 years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared with seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95% CI 1.30-4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95% CI 1.26-4.87), 3.12 (95% CI 1.28-7.61), and 2.30 (95% CI 1.09-4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality OR 1.99, 95% CI 1.21-3.27 for RF+ vs. RF-; OR 1.67, 95% CI 1.03-2.69 for CCP+ vs. CCP-) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend < 0.05). CONCLUSIONS Seropositive RA patients had two-fold increased risk for abnormalities on PFTs performed for clinical indications compared with seronegative RA. Patients with seropositive RA, particularly those with high-titer RF positivity, may be more likely to have obstructive and restrictive abnormalities, independent of smoking.Key points• Due to the known excess pulmonary morbidity/mortality in RA, we studied the relationship of rheumatoid arthritis (RA)-related autoantibodies with pulmonary function test (PFT) abnormalities using a large RA registry.• We evaluated whether presence and levels of cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were associated with restriction, obstruction, and diffusion abnormalities on PFTs among 1272 subjects with RA.• Seropositivity was associated with two-fold increased risk for any PFT abnormality, independent of confounders including smoking. Higher titers of RF conferred greatest risk for all PFT outcomes: obstruction, restriction, and diffusion abnormality.• These results provide evidence that patients with RA should be closely monitored for pulmonary involvement, particularly those with high-titer RF seropositivity.
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Affiliation(s)
- Sicong Huang
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA.
- Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
| | - Xintong He
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Tracy J Doyle
- Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
| | - Alessandra Zaccardelli
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Allison A Marshall
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
- Tufts School of Medicine, 145 Harrison Avenue, Boston, MA, 02111, USA
| | - H Maura Friedlander
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Rachel B Blaustein
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Elisabeth A Smith
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Jing Cui
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Christine K Iannaccone
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Taysir G Mahmoud
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
| | - Michael E Weinblatt
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
- Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA
| | - Paul F Dellaripa
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
- Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA
| | - Nancy A Shadick
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA
- Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA
| | - Jeffrey A Sparks
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA.
- Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
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34
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Esposito AJ, Chu SG, Madan R, Doyle TJ, Dellaripa PF. Thoracic Manifestations of Rheumatoid Arthritis. Clin Chest Med 2019; 40:545-560. [PMID: 31376890 DOI: 10.1016/j.ccm.2019.05.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Rheumatoid arthritis (RA) is commonly associated with pulmonary disease that can affect any anatomic compartment of the thorax. The most common intrathoracic manifestations of RA include interstitial lung disease, airway disease, pleural disease, rheumatoid nodules, and drug-induced toxicity. Patients with RA with thoracic involvement often present with nonspecific respiratory symptoms, although many are asymptomatic. Therefore, clinicians should routinely consider pulmonary disease when evaluating any patient with RA, particularly one with known risk factors. The optimal screening, diagnostic, and treatment strategies for RA-associated pulmonary disease remain uncertain and are the focus of ongoing investigation.
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Affiliation(s)
- Anthony J Esposito
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Sarah G Chu
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Rachna Madan
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Tracy J Doyle
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Paul F Dellaripa
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA.
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Kusmirek JE, Kanne JP. Thoracic Manifestations of Connective Tissue Diseases. Semin Ultrasound CT MR 2019; 40:239-254. [DOI: 10.1053/j.sult.2018.12.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Lee JS, Lee EY, Ha YJ, Kang EH, Lee YJ, Song YW. Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease. Arthritis Res Ther 2019; 21:58. [PMID: 30764869 PMCID: PMC6376648 DOI: 10.1186/s13075-019-1835-9] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 01/23/2019] [Indexed: 01/05/2023] Open
Abstract
Background Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters. Methods This retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%). Results CTD-ILD patients (n = 165) had elevated serum KL-6 levels compared to CTD patients without ILD (n = 384) (p < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) (p < 0.001) and forced vital capacity (FVC) (p < 0.001) parameters had a moderate, negative correlation with the KL-6 level. Conclusion Serum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity. Electronic supplementary material The online version of this article (10.1186/s13075-019-1835-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jeong Seok Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
| | - Eun Young Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
| | - You-Jung Ha
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea
| | - Eun Ha Kang
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea
| | - Yun Jong Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea
| | - Yeong Wook Song
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
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Olson AL, Gifford AH, Inase N, Fernández Pérez ER, Suda T. The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype. Eur Respir Rev 2018; 27:27/150/180077. [DOI: 10.1183/16000617.0077-2018] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 11/21/2018] [Indexed: 12/21/2022] Open
Abstract
The availability of epidemiological data relating to interstitial lung diseases (ILDs) has increased over recent years, but information on the prevalence and incidence of ILDs of different aetiologies remains limited. Despite global distribution, the proportion of patients who develop a progressive phenotype across different ILDs is not well known. Disease behaviour is well documented in idiopathic pulmonary fibrosis but idiosyncratic in other ILDs that may present a progressive fibrosing phenotype. Possible reasons may include the heterogeneous nature of the aetiology, the complexity of diagnosis (and subsequent documentation of cases) and the methods employed to retrospectively analyse patient databases. This review presents a broad overview of the epidemiological data available for ILDs that may present a progressive-fibrosing phenotype, collectively and stratified according to clinical classification. We also note where further data are needed in comparison to the well-studied IPF indication.
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Partington R, Helliwell T, Muller S, Abdul Sultan A, Mallen C. Comorbidities in polymyalgia rheumatica: a systematic review. Arthritis Res Ther 2018; 20:258. [PMID: 30458857 PMCID: PMC6247740 DOI: 10.1186/s13075-018-1757-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 10/31/2018] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND AND AIM Comorbidities are known to exist in many rheumatological conditions. Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition affecting older people which, prior to effective treatment, causes severe disability. Our understanding of associated comorbidities in PMR is based only on case reports or series and small cohort studies. The objective of this study is to review systematically the existing literature on the comorbidities associated with PMR. METHODS MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched for original observational research from inception to November 2016. Papers containing the words 'Polymyalgia Rheumatica' OR 'Giant Cell Arteritis' OR the terms 'PMR' OR 'GCA' were included. Article titles were reviewed based on pre-defined criteria by two reviewers. Following selection for inclusion, studies were quality assessed using the Newcastle-Ottawa tool and data were extracted. RESULTS A total of 17,329 papers were reviewed and 41 were incorporated in this review, including three published after the search took place. Wide variations were found in study design, comorbidities reported and populations studied. Positive associations were found between PMR diagnosis and stroke, cardiovascular disease, peripheral arterial disease, diverticular disease and hypothyroidism. Two studies reported a positive association between PMR and overall malignancy rate. Seven studies reported an association between PMR and specific types of cancer, such as leukaemia, lymphoma, myeloproliferative disease and specified solid tumours, although nine studies found either no or negative association between cancer and PMR. CONCLUSION Quantification of the prevalence of comorbidities in PMR is important to accurately plan service provision and enable identification of cases of PMR which may be more difficult to treat. This review highlights that research into comorbidities in PMR is, overall, methodologically inadequate and does not comprehensively cover all comorbidities. Future studies should consider a range of comorbidities in patients with a validated diagnosis of PMR in representative populations.
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Affiliation(s)
- Richard Partington
- Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, ST5 5BG UK
| | - Toby Helliwell
- Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, ST5 5BG UK
| | - Sara Muller
- Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, ST5 5BG UK
| | - Alyshah Abdul Sultan
- Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, ST5 5BG UK
| | - Christian Mallen
- Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, ST5 5BG UK
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Wakabayashi A, Ishiguro T, Takaku Y, Miyahara Y, Kagiyama N, Takayanagi N. Clinical characteristics and prognostic factors of pneumonia in patients with and without rheumatoid arthritis. PLoS One 2018; 13:e0201799. [PMID: 30075013 PMCID: PMC6075779 DOI: 10.1371/journal.pone.0201799] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Accepted: 07/23/2018] [Indexed: 12/20/2022] Open
Abstract
Background To elucidate the characteristics of pneumonia in rheumatoid arthritis (RA) patients and to assess whether pneumonia in RA patients differs from that in non-RA patients. Methods We retrospectively divided pneumonia patients into two groups, those with RA and those without RA, and compared the two groups. We evaluated the risk factors for mortality with univariate and multivariate logistic regression analysis. Results Among 1549 patients, 71 had RA. The RA patients with pneumonia were 71.0±8.9 years old, 54.9% were female, 40.9% had a smoking history, and 71.8% had underlying respiratory disease. Female sex, non-smoker, and respiratory comorbidities were statistically more frequent in the RA patients than non-RA patients. The most frequent causative microbial agents of pneumonia in the RA patients were Streptococcus pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Mycoplasma pneumoniae, and influenza virus, whereas those of pneumonia in non-RA patients were S. pneumoniae, influenza virus, M. pneumoniae, Legionella spp., P. aeruginosa, H. influenzae, and Moraxella catarrhalis. Polymicrobial infection were identified as etiologies more frequently in the RA patients than non-RA patients. Although the severity of pneumonia did not differ between the two groups, mortality was statistically higher in the RA patients than non-RA patients. Multivariate analysis showed RA to be an independent risk factor for mortality. Conclusions P. aeruginosa, H. influenzae, M. catarrhalis, and polymicrobial infection were statistically more frequent etiologies of pneumonia in the RA patients than non-RA patients. RA itself was found to be an independent risk factor for mortality from pneumonia.
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Affiliation(s)
- Aya Wakabayashi
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama, Japan
- * E-mail:
| | - Takashi Ishiguro
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama, Japan
| | - Yotaro Takaku
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama, Japan
| | - Yosuke Miyahara
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama, Japan
| | - Naho Kagiyama
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama, Japan
| | - Noboru Takayanagi
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama, Japan
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Lin E, Limper AH, Moua T. Obliterative bronchiolitis associated with rheumatoid arthritis: analysis of a single-center case series. BMC Pulm Med 2018; 18:105. [PMID: 29929518 PMCID: PMC6013859 DOI: 10.1186/s12890-018-0673-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Accepted: 06/13/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a systemic autoimmune condition characterized by erosive inflammation of the joints. One rare pulmonary manifestation is obliterative bronchiolitis (OB), a small airways disease characterized by the destruction of bronchiolar epithelium and airflow obstruction. METHODS We retrospectively reviewed the clinical data of patients with rheumatoid arthritis-associated obliterative bronchiolitis (RA-OB) from 01/01/2000 to 12/31/2015. Presenting clinical features, longitudinal pulmonary function testing, radiologic findings, and independent predictors of all-cause mortality were assessed. RESULTS Forty one patients fulfilled criteria for diagnosis of RA-OB. There was notable female predominance (92.7%) with a mean age of 57 ± 15 years. Dyspnea was the most common presenting clinical symptom. Median FEV1 was 40% (IQR 31-52.5) at presentation, with a mean decline of - 1.5% over a follow-up period of thirty-three months. Associated radiologic findings included mosaic attenuation and pulmonary nodules. A majority of patients (78%) received directed therapy including long-acting inhalers, systemic corticosteroids or other immunosuppressive agents, and macrolide antibiotics. All-cause mortality was 27% over a median follow-up of sixty-two months (IQR 32-113). No distinguishable predictors of survival at presentation were found. CONCLUSIONS RA-OB appears to have a stable clinical course in the majority of patients despite persistent symptoms and severe obstruction based on presenting FEV1.
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Affiliation(s)
- Erica Lin
- Department of Internal Medicine, 200 First St. SW, Rochester, MN, 55905, USA
| | - Andrew H Limper
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Teng Moua
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
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Burmester GR, McInnes IB, Kremer JM, Miranda P, Vencovský J, Godwood A, Albulescu M, Michaels MA, Guo X, Close D, Weinblatt M. Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor α Monoclonal Antibody: Long-Term Safety and Efficacy in Patients With Rheumatoid Arthritis. Arthritis Rheumatol 2018; 70:679-689. [PMID: 29361199 PMCID: PMC5947536 DOI: 10.1002/art.40420] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 01/11/2018] [Indexed: 12/15/2022]
Abstract
Objective Mavrilimumab, a human monoclonal antibody, targets granulocyte–macrophage colony‐stimulating factor receptor α. We undertook to determine the long‐term safety and efficacy of mavrilimumab in rheumatoid arthritis patients in 2 phase IIb studies (1071 and 1107) and in 1 open‐label extension study (ClinicalTrials.gov identifier: NCT01712399). Methods In study 1071, patients with an inadequate response to disease‐modifying antirheumatic drugs (DMARDs) received mavrilimumab (30, 100, or 150 mg) or placebo every other week plus methotrexate. In study 1107, patients with an inadequate response to anti–tumor necrosis factor agents and/or DMARDs received 100 mg mavrilimumab every other week or 50 mg golimumab every 4 weeks plus methotrexate. Patients entering the open‐label extension study received 100 mg mavrilimumab every other week plus methotrexate. Long‐term safety and efficacy of mavrilimumab were assessed. Results A total of 442 patients received mavrilimumab (14 of 245 patients from study 1071, 9 of 70 patients from study 1107, and 52 of 397 patients from the open‐label extension study discontinued mavrilimumab treatment throughout the studies). The cumulative safety exposure was 899 patient‐years; the median duration of mavrilimumab treatment was 2.5 years (range 0.1–3.3 years). The most common treatment‐emergent adverse events (AEs) were nasopharyngitis (n = 69; 7.68 per 100 patient‐years) and bronchitis (n = 51; 5.68 per 100 patient‐years). At weeks 74 and 104, 3.5% and 6.2% of patients, respectively, demonstrated reduction in forced expiratory volume in 1 second, while 2.9% and 3.4% of patients, respectively, demonstrated reduction in forced vital capacity (>20% reduction from baseline to <80% predicted). Most pulmonary changes were transient and only infrequently associated with AEs. Mavrilimumab at 100 mg every other week demonstrated sustained efficacy; at week 122, 65.0% of patients achieved a Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) of <3.2, and 40.6% of patients achieved a DAS28‐CRP of <2.6. Conclusion Long‐term treatment with mavrilimumab maintained response and was well‐tolerated with no increased incidence of treatment‐emergent AEs. Safety data were comparable with those from both phase IIb qualifying studies.
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Kanıtez NA, Çelik S, Öner SY, Ürer HN, Bes C, Çetinkaya E. Cavitary pulmonary nodules in rheumatoid arthritis; case reports and review of the literature. Eur J Rheumatol 2018; 5:65-68. [PMID: 30501854 DOI: 10.5152/eurjrheum.2017.16106] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 02/17/2017] [Indexed: 11/22/2022] Open
Abstract
Rheumatoid nodules are the most common pulmonary manifestations of rheumatoid arthritis (RA) and are usually asymptomatic. In rare cases, they progress cavitary formation and cause severe clinical symptoms because of disease activity, infectious diseases, and other etiologies. The determination of clinical and histopathological features may be helpful for differential diagnosis in patients with RA with cavitary pulmonary nodules. Herein, we report two female patients with RA with cavitary pulmonary nodules and aim to obtain more detail data by means of reviewing previously reported cases.
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Affiliation(s)
- Nilüfer Alpay Kanıtez
- Department of Rheumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Selda Çelik
- Department of Rheumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Sibel Yılmaz Öner
- Department of Rheumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Halide Nur Ürer
- Department of Pathology, Yedikule Chest Diseases Training and Research Hospital, İstanbul, Turkey
| | - Cemal Bes
- Department of Rheumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Erdoğan Çetinkaya
- Department of Chest Disease, Yedikule Chest Diseases Training and Research Hospital, İstanbul, Turkey
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Kristen Demoruelle M, Olson AL, Solomon JJ. The Epidemiology of Rheumatoid Arthritis-Associated Lung Disease. LUNG DISEASE IN RHEUMATOID ARTHRITIS 2018. [DOI: 10.1007/978-3-319-68888-6_4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Doyle TJ, Dellaripa PF, Rosas IO. Risk Factors and Biomarkers of RA-ILD. LUNG DISEASE IN RHEUMATOID ARTHRITIS 2018. [DOI: 10.1007/978-3-319-68888-6_5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Brito Y, Glassberg MK, Ascherman DP. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Current Concepts. Curr Rheumatol Rep 2017; 19:79. [PMID: 29119259 DOI: 10.1007/s11926-017-0701-5] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW Among the many extra-articular complications of rheumatoid arthritis (RA), interstitial lung disease (ILD) contributes significantly to morbidity and mortality. Prevalence estimates for RA-ILD vary widely depending on the specific clinical, radiographic, and functional criteria used to establish the diagnosis. A key unresolved issue is whether early, subclinical forms of RA-ILD represent a precursor to end stage, fibrotic lung disease. Based on uncertainties surrounding the natural history of RA-ILD, incomplete understanding of underlying disease pathogenesis, and lack of controlled clinical trials, evidence-based therapeutic strategies remain largely undefined. RECENT FINDINGS Correlative clinico-epidemiological studies have identified key risk factors for disease progression. Complementing these findings, the identification of specific molecular and serological markers of RA-ILD has improved our understanding of disease pathogenesis and established the foundation for predictive biomarker profiling. Experience from case series and cohort studies suggests that newer biological agents such as rituximab may be viable treatment options. RA-ILD continues to have a major impact on "disease intrinsic" morbidity and mortality. Increased understanding of disease pathogenesis and the natural history of subclinical RA-ILD will promote the development of more refined therapeutic strategies.
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Affiliation(s)
- Yoel Brito
- Division of Pulmonary and Critical Care Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Marilyn K Glassberg
- Division of Pulmonary and Critical Care Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Dana P Ascherman
- Division of Rheumatology, University of Miami Miller School of Medicine, Rosenstiel Medical Science Building, 7152, 1600 NW 10th Avenue, Miami, FL, 33136-1050, USA.
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Vogel MNA, Kreuter M, Kauczor HU, Heußel CP. [Pulmonary manifestations in collagen vascular diseases]. Radiologe 2017; 56:910-916. [PMID: 27659711 DOI: 10.1007/s00117-016-0157-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
CLINICAL/METHODICAL ISSUE Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. STANDARD RADIOLOGICAL METHODS The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. PERFORMANCE The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. ACHIEVEMENTS Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. PRACTICAL RECOMMENDATIONS At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management.
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Affiliation(s)
- M N A Vogel
- Abteilung für Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Thoraxklinik, Universitätsklinikum Heidelberg, Röntgenstr. 1, 69126, Heidelberg, Deutschland. .,Translational Lung Research Center (TLRC), Universitätsklinikum Heidelberg, Heidelberg, Deutschland.
| | - M Kreuter
- Zentrum für interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland.,Translational Lung Research Center (TLRC), Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - H-U Kauczor
- Abteilung für Diagnostische und Interventionelle Radiologie, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland.,Translational Lung Research Center (TLRC), Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C-P Heußel
- Abteilung für Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Thoraxklinik, Universitätsklinikum Heidelberg, Röntgenstr. 1, 69126, Heidelberg, Deutschland.,Abteilung für Diagnostische und Interventionelle Radiologie, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland.,Translational Lung Research Center (TLRC), Universitätsklinikum Heidelberg, Heidelberg, Deutschland
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Relationship between matrix metalloproteinase-3 serum level and pulmonary artery systolic pressure in patients with rheumatoid arthritis. Heart Vessels 2017; 33:191-197. [DOI: 10.1007/s00380-017-1045-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 08/18/2017] [Indexed: 10/19/2022]
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Recent advances in the pathogenesis, prediction, and management of rheumatoid arthritis-associated interstitial lung disease. Curr Opin Rheumatol 2017; 29:254-259. [PMID: 28207496 DOI: 10.1097/bor.0000000000000380] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW To provide an overview of recently published articles covering interstitial lung disease associated with rheumatoid arthritis (RA-ILD). RECENT FINDINGS Over the past year, many studies replicated previous findings in more diverse and occasionally larger populations internationally. Specifically, the association among cigarette smoking, high rheumatoid factor titer, elevated anticitrullinated protein antibody (ACPA) levels, and RA-ILD was strengthened. Clinical characteristics, autoantibodies, and biomarkers to aid in RA-ILD development, progression, and mortality prediction were explored. Finally, direct and indirect treatment effects were highlighted. SUMMARY The ability to identify risk factors for preclinical RA-ILD has been enhanced, but the proper management strategy for these patients is yet to be defined. ACPAs and cigarette smoking are highly associated with RA-ILD, but the mechanistic relationship between lung injury and autoantibody generation remains unknown. There is conflicting evidence regarding the significance of a usual interstitial pneumonia (UIP) versus non-UIP pattern on high-resolution computed tomography. The use of biologic agents in patients with rheumatoid arthritis does not appear to increase the risk of incident ILD or RA-ILD exacerbation. Randomized prospective studies of specific therapy for RA-ILD are still lacking.
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Chaudhry AA, Gul M, Chaudhry AA, Moore W. Case 238: Spontaneous Pneumothorax Secondary to Intrapulmonary Necrobiotic Rheumatoid Nodule. Radiology 2017; 282:602-608. [PMID: 28099107 DOI: 10.1148/radiol.2016150224] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
History A 54-year-old white woman with a history of rheumatoid arthritis who was taking glucocorticoids and methotrexate presented to the emergency department in December with worsening shortness of breath and chest heaviness for 1 week. She reported additional symptoms of weakness, headache, and arthralgia primarily involving her bilateral hands, wrist, ankles, and feet. She denied experiencing fevers, syncope or presyncope, focal neurologic deficits, chest pain, nausea, vomiting, unintentional weight loss, or recent trauma. Additional medical history included hypertension, asthma, degenerative disk disease, and migraine, all of which were reportedly controlled with medications. This patient had a smoking history of 80 pack-years, but she had quit smoking 2 months prior to presentation. She denied abuse of alcohol or recreational drugs and reported she was up-to-date on her immunizations, including those for pneumonia and flu. Family history was pertinent for breast cancer in her mother, sister, and maternal aunt. The patient reported normal findings at screening mammography and colonoscopy. A physical examination was remarkable for slightly asymmetric breath sounds, which appeared to be diminished on the right side. This patient had multiple joint deformities, most notably in the bilateral metacarpophalangeal joints. Initial electrocardiography findings and cardiac biomarkers were negative. Her complete blood count and basic metabolic profile were unremarkable. Posteroanterior and lateral chest radiographs were obtained in the emergency department. Subsequently, computed tomography (CT) of the chest was performed.
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Affiliation(s)
- Ammar A Chaudhry
- From the Department of Radiology, Stony Brook University Medical Center, HSC Level 4, Room 120, East Loop Road, Stony Brook, NY 11794 (Ammar A. Chaudhry, Abbas A. Chaudhry, W.M.); and Department of Internal Medicine, Winthrop University Hospital, Mineola, NY (M.G.)
| | - Maryam Gul
- From the Department of Radiology, Stony Brook University Medical Center, HSC Level 4, Room 120, East Loop Road, Stony Brook, NY 11794 (Ammar A. Chaudhry, Abbas A. Chaudhry, W.M.); and Department of Internal Medicine, Winthrop University Hospital, Mineola, NY (M.G.)
| | - Abbas A Chaudhry
- From the Department of Radiology, Stony Brook University Medical Center, HSC Level 4, Room 120, East Loop Road, Stony Brook, NY 11794 (Ammar A. Chaudhry, Abbas A. Chaudhry, W.M.); and Department of Internal Medicine, Winthrop University Hospital, Mineola, NY (M.G.)
| | - William Moore
- From the Department of Radiology, Stony Brook University Medical Center, HSC Level 4, Room 120, East Loop Road, Stony Brook, NY 11794 (Ammar A. Chaudhry, Abbas A. Chaudhry, W.M.); and Department of Internal Medicine, Winthrop University Hospital, Mineola, NY (M.G.)
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