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Kılıç ACK, Vasi İ, Kılıç HK, Erden A, Gündoğdu O, Kardaş RC, Küçük H, Alp GT, Bölek EÇ, Kesen S, Kaya M, Erbaş G, Öztürk MA. Is Myopenia or Myosteatosis Clinically Relevant in Systemic Sclerosis? Skeletal Muscle Assessment Using Computed Tomography. Acad Radiol 2025:S1076-6332(25)00134-5. [PMID: 40037937 DOI: 10.1016/j.acra.2025.02.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 02/11/2025] [Accepted: 02/15/2025] [Indexed: 03/06/2025]
Abstract
OBJECTIVES Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis, vascular damage, and immune dysregulation, often leading to muscle abnormalities. This study aimed to evaluate the prevalence of myopenia and myosteatosis in SSc patients using computed tomography (CT) and their associations with clinical features, including lung disease and esophageal dilatation. MATERIALS AND METHODS SSc patients followed at Gazi University Rheumatology Clinic (2000-2024) who had thoracic CT imaging were included. Muscle mass and density were assessed at the L1 vertebral level. Skeletal muscle area (SMA) and skeletal muscle radiation attenuation (SMRA) were measured to identify myopenia and myosteatosis. Lung disease involvement and widest esophageal diameter (WED) were assessed via CT. Statistical analyses explored correlations between muscle metrics and clinical variables, with multiple linear regression identifying predictors. RESULTS Among 95 patients (54.7% diffuse SSc, 45.3% limited SSc; mean age 57.04 ± 13.65 years; female-to-male ratio 8.5:1), myopenia and myosteatosis prevalence were 27.3% and 41.1%, respectively. Myosteatosis was associated with female sex (p = 0.001), older age (p = 0.001), higher BMI (p = 0.043), and inflammation markers (CRP, ESR). Myopenia correlated with BMI (p = 0.001) but not clinical outcomes. Higher WED correlated with lower SMRA (p = 0.001). BMI predicted muscle mass (R² = 0.42), while age, gender, and BMI determined SMRA (R² = 0.67, p < 0.001). CONCLUSIONS Myosteatosis was more prevalent and strongly associated with clinical features, including lung disease and esophageal dilatation, than myopenia, underscoring the importance of muscle quality.
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Affiliation(s)
- Atiye Cenay Karabörk Kılıç
- Department of Radiology, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (A.C.K.K., H.K.K., O.G., S.K., M.K., G.E.).
| | - İbrahim Vasi
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
| | - Hüseyin Koray Kılıç
- Department of Radiology, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (A.C.K.K., H.K.K., O.G., S.K., M.K., G.E.)
| | - Abdulsamet Erden
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
| | - Onur Gündoğdu
- Department of Radiology, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (A.C.K.K., H.K.K., O.G., S.K., M.K., G.E.)
| | - Rıza Can Kardaş
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
| | - Hamit Küçük
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
| | - Gizem Tuğçe Alp
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
| | - Ertuğrul Çağrı Bölek
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
| | - Sevcihan Kesen
- Department of Radiology, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (A.C.K.K., H.K.K., O.G., S.K., M.K., G.E.)
| | - Mustafa Kaya
- Department of Radiology, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (A.C.K.K., H.K.K., O.G., S.K., M.K., G.E.)
| | - Gonca Erbaş
- Department of Radiology, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (A.C.K.K., H.K.K., O.G., S.K., M.K., G.E.)
| | - Mehmet Akif Öztürk
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Emniyet Mahallesi, Mevlana Bulvarı No: 29, Yenimahalle, Ankara 06500, Türkiye (I.V., A.E., R.C.K., H.K., E.C.B., M.A.O.)
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Ho KJ, Muhammad LN, Khanh LN, Li XS, Carns M, Aren K, Kim SJ, Verma P, Hazen SL, Varga J. Elevated Circulating Levels of Gut Microbe-Derived Trimethylamine N-Oxide Are Associated with Systemic Sclerosis. J Clin Med 2024; 13:5984. [PMID: 39408044 PMCID: PMC11477889 DOI: 10.3390/jcm13195984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N-oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. Methods: This is an observational case:control study. Adults with SSc (n = 200) and non-SSc controls (n = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Results: Median TMAO concentration was higher (p = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Conclusions: Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted.
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Affiliation(s)
- Karen J. Ho
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA;
| | - Lutfiyya N. Muhammad
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA;
| | - Linh Ngo Khanh
- Department of Cardiovascular Surgery, Houston Methodist Hospital, Houston, TX 77030, USA;
| | - Xinmin S. Li
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (X.S.L.); (S.L.H.)
| | - Mary Carns
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; (M.C.); (K.A.)
| | - Kathleen Aren
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; (M.C.); (K.A.)
| | - Seok-Jo Kim
- Institute of Basic Science, Sungkyunkwan University, Suwon 16419, Republic of Korea;
- Mondrian AI Co., Ltd., Incheon 21985, Republic of Korea
| | - Priyanka Verma
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA;
| | - Stanley L. Hazen
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (X.S.L.); (S.L.H.)
- Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - John Varga
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA;
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De Angelis R, Cipolletta E, Francioso F, Carotti M, Farah S, Giovagnoni A, Salaffi F. Low-Carbon Monoxide Diffusing Capacity, Patient-Reported Measures and Reduced Nailfold Capillary Density Are Associated with Interstitial Lung Disease in Systemic Sclerosis. J Pers Med 2024; 14:635. [PMID: 38929856 PMCID: PMC11205232 DOI: 10.3390/jpm14060635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 06/08/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
The aim of this paper is to identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association for a personalised application in clinical practice. METHODS A total of 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. RESULTS Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p < 0.001) with a cut-off of ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg Scale showed an AUC of 0.883 (p < 0.001) with a cut-off >2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p < 0.001) with a cut-off >7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p < 0.001) with a cut-off of ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan's nomogram to calculate the post-test probability of this association. CONCLUSIONS Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients' characteristics, significantly increases the ability to find out the presence of SSc-ILD.
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Affiliation(s)
- Rossella De Angelis
- Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, “Carlo Urbani” Hospital, Jesi, 60035 Ancona, Italy; (E.C.); (F.F.); (S.F.); (F.S.)
- IRCCS INRCA, 60121 Ancona, Italy
| | - Edoardo Cipolletta
- Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, “Carlo Urbani” Hospital, Jesi, 60035 Ancona, Italy; (E.C.); (F.F.); (S.F.); (F.S.)
- Academic Rheumatology, University of Nottingham, Nottingham NG7 2RD, UK
| | - Francesca Francioso
- Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, “Carlo Urbani” Hospital, Jesi, 60035 Ancona, Italy; (E.C.); (F.F.); (S.F.); (F.S.)
| | - Marina Carotti
- Department of Radiology, “Ospedali Riuniti”, Polytechnic University of Marche, 60121 Ancona, Italy; (M.C.); (A.G.)
| | - Sonia Farah
- Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, “Carlo Urbani” Hospital, Jesi, 60035 Ancona, Italy; (E.C.); (F.F.); (S.F.); (F.S.)
| | - Andrea Giovagnoni
- Department of Radiology, “Ospedali Riuniti”, Polytechnic University of Marche, 60121 Ancona, Italy; (M.C.); (A.G.)
| | - Fausto Salaffi
- Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, “Carlo Urbani” Hospital, Jesi, 60035 Ancona, Italy; (E.C.); (F.F.); (S.F.); (F.S.)
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Ljilja Posavec A, Hrkač S, Tečer J, Huzjan Korunić R, Karanović B, Ježić I, Škopljanac I, Piskač Živković N, Mitrović J. Ultrasonic Evaluation of Diaphragm in Patients with Systemic Sclerosis. J Pers Med 2023; 13:1441. [PMID: 37888052 PMCID: PMC10608128 DOI: 10.3390/jpm13101441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/16/2023] [Accepted: 09/20/2023] [Indexed: 10/28/2023] Open
Abstract
The diaphragm is the most important muscle in respiration. Nevertheless, its function is rarely evaluated. Patients with systemic sclerosis (SSc) could be at risk of diaphragmatic dysfunction because of multiple factors. These patients often develop interstitial lung disease (SSc-ILD) and earlier studies have indicated that patients with different ILDs have decreased diaphragmatic mobility on ultrasound (US). This study aimed to evaluate diaphragmatic function in SSc patients using US with regard to the ILD, evaluated with the Warrick score on high-resolution computed tomography (HRCT), and to investigate associations between ultrasonic parameters and dyspnea, lung function, and other important clinical parameters. In this cross-sectional study, we analyzed diaphragm mobility, thickness, lung function, HRCT findings, Modified Medical Research Council (mMRC) dyspnea scale, modified Rodnan skin score (mRSS), autoantibodies, and esophageal diameters on HRCT in patients with SSc. Fifty patients were enrolled in the study. Patients with SSc-ILD had lower diaphragmatic mobility in deep breathing than patients without ILD. The results demonstrated negative correlations between diaphragmatic mobility and mMRC, mRSS, anti-Scl-70 antibodies, esophageal diameters on HRCT, and a positive correlation with lung function. Patients with SSc who experience dyspnea should be evaluated for diaphragmatic dysfunction for accurate symptom phenotyping and personalized pulmonary rehabilitation treatment.
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Affiliation(s)
- Anja Ljilja Posavec
- Polyclinic for Respiratory Diseases, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Stela Hrkač
- Division of Clinical Immunology, Allergology and Rheumatology, Department of Internal Medicine, Dubrava University Hospital, 10000 Zagreb, Croatia
| | - Josip Tečer
- Division of Clinical Immunology, Allergology and Rheumatology, Department of Internal Medicine, Dubrava University Hospital, 10000 Zagreb, Croatia
| | - Renata Huzjan Korunić
- Clinical Department of Diagnostic and Interventional Radiology, University Hospital Dubrava, 10000 Zagreb, Croatia
| | - Boris Karanović
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
| | - Ivana Ježić
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
| | - Ivan Škopljanac
- Department of Pulmonology, University Hospital Centre Split, 21000 Split, Croatia;
| | - Nevenka Piskač Živković
- Special Hospital Radiochirurgia Zagreb, 10000 Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
| | - Joško Mitrović
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Division of Clinical Immunology, Allergology and Rheumatology, Department of Internal Medicine, Dubrava University Hospital, 10000 Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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Volkmann ER, Tashkin DP, Leng M, Kim GHJ, Goldin J, Roth MD. Association of Symptoms of Gastroesophageal Reflux, Esophageal Dilation, and Progression of Systemic Sclerosis-Related Interstitial Lung Disease. Arthritis Care Res (Hoboken) 2023; 75:1690-1697. [PMID: 36504432 PMCID: PMC10258217 DOI: 10.1002/acr.25070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 11/15/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To investigate whether symptoms of gastroesophageal reflux disease and radiographic measures of esophageal dilation are associated with radiographic progression of systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS Participants of the Scleroderma Lung Study II, which compared mycophenolate versus cyclophosphamide for SSc-ILD, completed the reflux domain of the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 at baseline. The diameter and area of the esophagus in the region of maximum dilation was measured by quantitative image analysis. Univariate and multivariable linear regression analyses were created to evaluate the relationship between these measures of esophageal involvement and progression of SSc-ILD over 2 years, based on the radiologic quantitative interstitial lung disease (QILD) and quantitative lung fibrosis (QLF) in the lobe of maximum involvement (LM). All multivariable models controlled for the treatment arm, baseline ILD severity, and proton-pump inhibitor use. RESULTS The baseline mean patient-reported reflux score was 0.57, indicating moderate reflux (n = 141). Baseline mean maximal esophageal diameter and area were 22 mm and 242 mm2 , respectively. Baseline reflux scores were significantly associated with the change in QLF-LM and QILD-LM in the univariate and multivariable models. Neither radiographic measure of esophageal dilation was associated with the change in radiographic measures of lung involvement. CONCLUSION Severity of reflux symptoms as measured by an SSc-specific questionnaire was independently associated with the change in the radiographic extent of ILD and fibrosis over 2 years in patients with SSc-ILD. Two objective measures of esophageal dilation were not associated with radiographic progression of ILD, highlighting the need for improved objective measures of esophageal dysfunction in SSc.
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Affiliation(s)
- Elizabeth R. Volkmann
- Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; USA
| | - Donald P. Tashkin
- Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; USA
| | - Mei Leng
- Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; USA
| | - Grace Hyun J. Kim
- Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine; USA
| | - Jonathan Goldin
- Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine; USA
| | - Michael D. Roth
- Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; USA
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Chatterjee S, Perelas A, Yadav R, Kirby DF, Singh A. Viewpoint: a multidisciplinary approach to the assessment of patients with systemic sclerosis-associated interstitial lung disease. Clin Rheumatol 2023; 42:653-661. [PMID: 36271064 PMCID: PMC9935731 DOI: 10.1007/s10067-022-06408-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 10/05/2022] [Accepted: 10/07/2022] [Indexed: 11/03/2022]
Abstract
Systemic sclerosis (SSc) is a rare and heterogeneous disease affecting the skin and internal organs. SSc-associated ILD (SSc-ILD) is a common and often early manifestation of SSc. This article discusses the rationale for a multidisciplinary approach (MDA) to the early identification and assessment of patients with SSc-ILD. Diagnosis of SSc-ILD is often challenging as patients with early disease can be asymptomatic, and SSc-ILD symptoms, such as exertional dyspnea and cough, are non-specific. High-resolution computed tomography (HRCT) of the lungs is the gold standard for diagnosis of SSc-ILD since pulmonary function tests lack sensitivity and specificity, especially in early disease. On HRCT, most patients with SSc-ILD have a non-specific interstitial pneumonia (NSIP) pattern. In addition, findings of pulmonary hypertension and esophageal dysmotility may be present. The multi-organ involvement of SSc and the diverse spectrum of symptoms support an MDA for the diagnosis and assessment of patients with SSc-ILD, with input from rheumatologists, pulmonologists, gastroenterologists, radiologists, and other specialists. Key Points • Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc). • Early diagnosis is key to reducing the morbidity and mortality associated with SSc-ILD and other manifestations of SSc. • The multi-organ involvement of SSc supports a multidisciplinary approach to the diagnosis and assessment of patients with SSc-ILD, with input from rheumatologists, pulmonologists, gastroenterologists, radiologists, and other specialists.
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Affiliation(s)
- Soumya Chatterjee
- Department of Rheumatic and Immunologic Diseases, Orthopedic and Rheumatology Institute, Cleveland Clinic, Cleveland, OH USA
| | - Apostolos Perelas
- Department of Pulmonary and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA USA
| | - Ruchi Yadav
- Department of Diagnostic Radiology, Imaging Institute, Cleveland Clinic, Cleveland, OH USA
| | - Donald F. Kirby
- Department of Gastroenterology, Hepatology, and Nutrition, Center for Human Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH USA
| | - Amandeep Singh
- Department of Gastroenterology, Hepatology, and Nutrition, Center for Human Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH USA
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Pugnet G, Petermann A, Collot S, Otal P, Lansiaux P, Ait Abdallah N, Lorillon G, Resche-Rigon M, Borel C, Marjanovic Z, Farge D. Changes on chest HRCT in systemic sclerosis-related interstitial lung disease after autologous haematopoietic stem cell transplantation. Rheumatology (Oxford) 2023; 62:SI32-SI42. [PMID: 35686921 PMCID: PMC9910571 DOI: 10.1093/rheumatology/keac319] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/20/2022] [Accepted: 04/29/2022] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To evaluate extent of interstitial lung disease (ILD) and oesophageal involvement using high-resolution computed tomography (HRCT) in early diffuse SSc patients after autologous haematopoietic stem cell transplantation (aHSCT). METHODS Overall chest HRCT, lung function and skin score changes were evaluated in 33 consecutive diffuse SSc patients before and after aHSCT during yearly routine follow-up visits between January 2000 and September 2016. Two independent radiologists blindly assessed the ILD extent using semi-quantitative Goh and Wells method, the widest oesophageal diameter (WOD) and the oesophageal volume (OV) on HRCT. Patients were retrospectively classified as radiological responders or non-responders, based on achieved stability or a decrease of 5% or more of HRCT-ILD at 24 months post-aHSCT. RESULTS Using a linear mixed model, the regressions of the extent of ILD and of ground glass opacities were significant at 12 months (ILD P = 0.001; ground glass opacities P = 0.0001) and at 24 months (ILD P = 0.007; ground glass opacities P = 0.0008) after aHSCT, with 18 patients classified as radiological responders (probability of response 0.78 [95% CI 0.58, 0.90]). Meanwhile the WOD and the OV increased significantly at 12 months (WOD P = 0.03; OV P = 0.34) and at 24 months (WOD P = 0.002; OV P = 0.007). Kaplan-Meier analyses showed a trend towards better 5-year survival rates (100% vs 60%; hazard ratio 0.23 [95% CI 0.03, 1.62], P = 0.11) among radiological responders vs non-responders at 24 month follow-up after aHSCT. CONCLUSION Real-world data analysis confirmed significant improvement in extent of HRCT SSc-ILD 24 months after aHSCT, although oesophageal dilatation worsened requiring specific attention.
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Affiliation(s)
- Grégory Pugnet
- Service de Médecine Interne et Immunologie Clinique CHU Toulouse
- Centre d’Investigation Clinique module Biothérapies (CIC BT 1436)
| | | | - Samia Collot
- Service de Radiologie Centrale, CHU Toulouse, Toulouse
| | - Philippe Otal
- Service de Radiologie Centrale, CHU Toulouse, Toulouse
| | - Pauline Lansiaux
- Unité de Médecine Interne (UF 04): CRMR MATHEC, Maladies auto-immunes et thérapie cellulaire; Centre de Référence des Maladies auto-immunes systémiques Rares d’Ile-de-France MATHEC, AP-HP, Hôpital St-Louis
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, EA3518 (Equipe 3 MATHEC-EUROCORD), Paris
| | - Nassim Ait Abdallah
- Unité de Médecine Interne (UF 04): CRMR MATHEC, Maladies auto-immunes et thérapie cellulaire; Centre de Référence des Maladies auto-immunes systémiques Rares d’Ile-de-France MATHEC, AP-HP, Hôpital St-Louis
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, EA3518 (Equipe 3 MATHEC-EUROCORD), Paris
| | | | | | - Cécile Borel
- Service Hématologie clinique CHU Toulouse, Toulouse
| | - Zora Marjanovic
- Hématologie clinique et thérapie cellulaire-hôpital Saint-Antoine, AP-HP, Paris, France
| | - Dominique Farge
- Unité de Médecine Interne (UF 04): CRMR MATHEC, Maladies auto-immunes et thérapie cellulaire; Centre de Référence des Maladies auto-immunes systémiques Rares d’Ile-de-France MATHEC, AP-HP, Hôpital St-Louis
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, EA3518 (Equipe 3 MATHEC-EUROCORD), Paris
- Department of Medicine, McGill University, Montreal, Canada
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Roberson ED, Carns M, Cao L, Aren K, Goldberg IA, Morales-Heil DJ, Korman BD, Atkinson JP, Varga J. Alterations of the Primary Cilia Gene SPAG17 and SOX9 Locus Noncoding RNAs Identified by RNA-Sequencing Analysis in Patients With Systemic Sclerosis. Arthritis Rheumatol 2023; 75:108-119. [PMID: 35762854 PMCID: PMC10445493 DOI: 10.1002/art.42281] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 05/12/2022] [Accepted: 06/23/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Systemic sclerosis (SSc) is characterized by immune activation, vasculopathy, and unresolving fibrosis in the skin, lungs, and other organs. We performed RNA-sequencing analysis on skin biopsy samples and peripheral blood mononuclear cells (PBMCs) from SSc patients and unaffected controls to better understand the pathogenesis of SSc. METHODS We analyzed these data 1) to test for case/control differences and 2) to identify genes whose expression levels correlate with SSc severity as measured by local skin score, modified Rodnan skin thickness score (MRSS), forced vital capacity (FVC), or diffusing capacity for carbon monoxide (DLco). RESULTS We found that PBMCs from SSc patients showed a strong type I interferon signature. This signal was found to be replicated in the skin, with additional signals for increased extracellular matrix (ECM) genes, classical complement pathway activation, and the presence of B cells. Notably, we observed a marked decrease in the expression of SPAG17, a cilia component, in SSc skin. We identified genes that correlated with the MRSS, DLco, and FVC in SSc PBMCs and skin using weighted gene coexpression network analysis. These genes were largely distinct from the case/control differentially expressed genes. In PBMCs, type I interferon signatures negatively correlated with the DLco. In SSc skin, ECM gene expression positively correlated with the MRSS. Network analysis of SSc skin genes that correlated with clinical features identified the noncoding RNAs SOX9-AS1 and ROCR, both near the SOX9 locus, as highly connected, "hub-like" genes in the network. CONCLUSION These results identify noncoding RNAs and SPAG17 as novel factors potentially implicated in the pathogenesis of SSc.
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Affiliation(s)
- Elisha D.O. Roberson
- Department of Medicine, Division of Rheumatology, Washington University, St. Louis, MO, USA
- Department of Genetics, Washington University, St. Louis, MO, USA
| | - Mary Carns
- Feinberg School of Medicine, Scleroderma Program, Northwestern University, Chicago, IL, USA
| | - Li Cao
- Department of Medicine, Division of Rheumatology, Washington University, St. Louis, MO, USA
| | - Kathleen Aren
- Feinberg School of Medicine, Scleroderma Program, Northwestern University, Chicago, IL, USA
| | - Isaac A. Goldberg
- Feinberg School of Medicine, Scleroderma Program, Northwestern University, Chicago, IL, USA
| | - David J. Morales-Heil
- Department of Medicine, Division of Rheumatology, Washington University, St. Louis, MO, USA
| | - Benjamin D. Korman
- Feinberg School of Medicine, Scleroderma Program, Northwestern University, Chicago, IL, USA
| | - John P. Atkinson
- Department of Medicine, Division of Rheumatology, Washington University, St. Louis, MO, USA
| | - John Varga
- Feinberg School of Medicine, Scleroderma Program, Northwestern University, Chicago, IL, USA
- Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA
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9
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Liu P, Chai J, Dai L, Chen B, Zhao J, Lu M, Zeng L, Xia Z, Mu R. Development of a Diagnostic Model Focusing on Esophageal Dysmotility in Patients with Systemic Sclerosis. Diagnostics (Basel) 2022; 12:diagnostics12123142. [PMID: 36553149 PMCID: PMC9776849 DOI: 10.3390/diagnostics12123142] [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: 11/10/2022] [Revised: 12/06/2022] [Accepted: 12/11/2022] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Esophageal dysmotility is a common and neglected complication of systemic sclerosis (SSc) associated with poor prognosis, while the assessment remains a challenge. We aimed to develop a diagnostic model for esophageal dysmotility in SSc patients that provides individualized risk estimates. METHODS Seventy-five SSc patients who underwent high-resolution manometry (HRM) were included in the study. Esophageal widest diameter (WED) was measured on a chest CT scan. Esophageal parameters between patients with and without esophageal dysmotility were compared. Multivariate logistic regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to fit the model. The diagnostic model was evaluated by discrimination and calibration. Internal validation was estimated using the enhanced bootstrap method with 1000 repetitions. RESULTS Sixty-one systemic sclerosis patients (81.3%) were diagnosed with esophageal dysmotility according to the Chicago Classification v 3.0. The diagnostic model for evaluating the probability of esophageal dysmotility integrated clinical and imaging features, including disease duration, ILD, and WED. The model displayed good discrimination with an area under the curve (AUC) of 0.923 (95% CI: 0.837-1.000), a Brier score of 0.083, and good calibration. A high AUC value of 0.911 could still be achieved in the internal validation. CONCLUSION The diagnostic model, which combines the disease duration, ILD, and imaging feature (WED), is an effective and noninvasive method for predicting esophageal dysmotility in SSc patients.
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Affiliation(s)
- Peiling Liu
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Jing Chai
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Liyi Dai
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Beidi Chen
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Jinxia Zhao
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Ming Lu
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
- Department of Infectious Diseases, Peking University Third Hospital, Beijing 100191, China
| | - Lin Zeng
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
| | - Zhiwei Xia
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Rong Mu
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
- Correspondence:
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10
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Aurangabadkar GM, Aurangabadkar MY, Choudhary SS, Ali SN, Khan SM, Jadhav US. Pulmonary Manifestations in Rheumatological Diseases. Cureus 2022; 14:e29628. [PMID: 36321051 PMCID: PMC9612897 DOI: 10.7759/cureus.29628] [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: 08/30/2022] [Accepted: 09/26/2022] [Indexed: 11/06/2022] Open
Abstract
Pulmonary involvement complicates the various aspects of care in patients suffering from autoimmune disorders. The epidemiological data generated over the last 10 to 15 years have improved the overall understanding of the risk factors and pathophysiological mechanisms involved in pulmonary involvement in rheumatological conditions. Recent advances in genetics have provided superior insight into the pathogenesis of autoimmune diseases and the underlying pulmonary involvement. This review article provides a concise overview of the four most common rheumatological conditions associated with pulmonary involvement: systemic lupus erythematosus (SLE), dermatomyositis/polymyositis, rheumatoid arthritis (RA), and systemic sclerosis (SSc). The clinical, epidemiological, and genetic aspects of these diseases are summarized in this article with particular emphasis on the characteristic patterns of pulmonary involvement in radiological imaging and various treatment options for each of these autoimmune diseases and their lung manifestations.
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11
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Carlson DA, Prescott JE, Germond E, Brenner D, Carns M, Correia CS, Tetreault MP, McMahan ZH, Hinchcliff M, Kou W, Kahrilas PJ, Perlman HR, Pandolfino JE. Heterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of "scleroderma esophagus". Neurogastroenterol Motil 2022; 34:e14284. [PMID: 34709690 PMCID: PMC9046463 DOI: 10.1111/nmo.14284] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/27/2021] [Accepted: 10/12/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND Although esophageal dysmotility is common in systemic sclerosis (SSc)/scleroderma, little is known regarding the pathophysiology of motor abnormalities driving reflux severity and dysphagia. This study aimed to assess primary and secondary peristalsis in SSc using a comprehensive esophageal motility assessment applying high-resolution manometry (HRM) and functional luminal imaging probe (FLIP) Panometry. METHODS A total of 32 patients with scleroderma (28 female; ages 38-77; 20 limited SSc, 12 diffuse SSc) completed FLIP Panometry and HRM. Secondary peristalsis, i.e., contractile responses (CR), was classified on FLIP Panometry by pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), or absent (ACR). Primary peristalsis on HRM was assessed according to the Chicago classification. RESULTS The manometric diagnoses were 56% (n = 18) absent contractility, 22% (n = 7) ineffective esophageal motility (IEM), and 22% (n = 7) normal motility. Secondary peristalsis (CRs) included 38% (n = 12) ACR, 38% (n = 12) IDCR, 19% (n = 6) BCR, and 15% (n = 5) NCR. The median (IQR) esophagogastric junction (EGJ) distensibility index (DI) was 5.8 mm2 /mmHg (4.8-10.1) mm2 /mmHg; EGJ-DI was >8.0 mm2 /mmHg in 31%, and >2.0 mm2 /mmHg in 100% of patients. Among 18 patients with absent contractility on HRM, 11 had ACR, 5 had IDCR, and 2 had BCR. Among 7 patients with IEM, 1 had ACR, 5 had IDCR, and 1 NCR. All of the patients with normal peristalsis had NCR or BCR. CONCLUSIONS This was the first study assessing combined HRM and FLIP Panometry in a cohort of SSc patients, which demonstrated heterogeneity in primary and secondary peristalsis. This complementary approach facilitates characterizing esophageal function in SSc, although future study to examine clinical outcomes remains necessary.
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Affiliation(s)
- Dustin A. Carlson
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jacqueline E Prescott
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Emma Germond
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Darren Brenner
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Mary Carns
- Department of Medicine, Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Chase S. Correia
- Department of Medicine, Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Marie-Pier Tetreault
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Zsuzsanna H. McMahan
- Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Monique Hinchcliff
- Department of Internal Medicine, Division of Rheumatology, Allergy, and Immunology, Yale School of Medicine, New Haven, CT, USA
| | - Wenjun Kou
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Peter J Kahrilas
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Harris R. Perlman
- Department of Medicine, Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - John E. Pandolfino
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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12
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Castelino FV, VanBuren JM, Startup E, Assassi S, Bernstein EJ, Chung L, Correia C, Evnin LB, Frech TM, Gordon JK, Hant FN, Hummers LK, Khanna D, Sandorfi N, Shah AA, Shanmugam VK, Steen V. Baseline characteristics of systemic sclerosis patients with restrictive lung disease in a multi-center US-based longitudinal registry. Int J Rheum Dis 2022; 25:163-174. [PMID: 34841681 DOI: 10.1111/1756-185x.14253] [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: 06/30/2021] [Revised: 11/12/2021] [Accepted: 11/12/2021] [Indexed: 11/29/2022]
Abstract
AIM Interstitial lung disease (ILD) is the leading cause of disease-related death in systemic sclerosis (SSc). Here, we assess baseline characteristics of SSc subjects with and without restrictive lung disease (RLD) in a multi-center, US-based registry. METHODS SSc patients within 5 years of disease onset were enrolled in the Collaborative National Quality and Efficacy Registry (CONQUER), a multi-center US-based registry of SSc study participants (age ≥ 18 years) enrolled at 13 expert centers. All subjects met 2013 American College of Rheumatology / European League Against Rheumatism criteria. Subjects with a pulmonary function test (PFT) at baseline before April 1, 2020 were included. High-resolution computed tomography scan of the chest was not available to characterize ILD for all subjects. RLD was defined as forced vital capacity (FVC) <80% or total lung capacity (TLC) <80% predicted. RESULTS There were 160 (45%) SSc subjects characterized as having RLD. There was no significant difference in age, gender or disease duration. RLD subjects had a mean disease duration from date of first non-Raynaud's symptom of 2.6 years and a mean FVC% predicted of 67% at baseline. In multivariable analysis, non-White race, higher physician global health assessment and modified Medical Research Council (mMRC) dyspnea scores, were independently associated with RLD. In the subgroup of RLD subjects with ILD, ILD had a negative correlation with RNA polymerase III antibody. CONCLUSION CONQUER is the largest, multi-center, prospective cohort of early SSc patients in the US. Non-White race was independently associated with RLD. In addition, 45% of CONQUER subjects already had RLD, highlighting the importance of screening for SSc-ILD at initial diagnosis.
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Affiliation(s)
- Flavia V Castelino
- Division of Rheumatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - John M VanBuren
- Department or Pediatrics, University of Utah, Salt Lake City, Utah, USA
| | - Emily Startup
- Department or Pediatrics, University of Utah, Salt Lake City, Utah, USA
| | - Shervin Assassi
- The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Elana J Bernstein
- Division of Rheumatology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA
| | - Lorinda Chung
- Division of Rheumatology, Department of Medicine and Dermatology, Stanford University and Palo Alto Veterans Affairs Health Care System, Stanford, California, USA
| | - Chase Correia
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Luke B Evnin
- Scleroderma Research Foundation, San Francisco, California, USA
| | - Tracy M Frech
- Division of Rheumatology, Department of Internal Medicine, University of Utah and Salt Lake Veterans Affair Medical Center, Salt Lake City, Utah, USA
| | | | - Faye N Hant
- Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Laura K Hummers
- Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Dinesh Khanna
- University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA
| | - Nora Sandorfi
- Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ami A Shah
- Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Victoria K Shanmugam
- Division of Rheumatology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
| | - Virginia Steen
- Georgetown University School of Medicine, Washington, District of Columbia, USA
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13
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Renaud A, Pautre R, Morla O, Achille A, Durant C, Espitia O, Frampas E, Agard C. Thoracic lymphadenopathies in diffuse systemic sclerosis: an observational study on 48 patients using computed tomography. BMC Pulm Med 2022; 22:44. [PMID: 35078448 PMCID: PMC8788097 DOI: 10.1186/s12890-022-01837-y] [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: 03/20/2021] [Accepted: 01/05/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Thoracic multidetector computed tomography (MDCT) is essential for the detection of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Thoracic MDCT assessment can reveal the presence of thoracic lymphadenopathies (LAP) whose signification remains uncertain. The purpose of the study was to describe the characteristics and to assess the significance of thoracic LAP in patients with diffuse SSc.
Methods
We conducted a monocentric observational study on adult patients with diffuse SSc, and collected general patient and first thoracic MDCT characteristics, PET-CT and outcome data. Comparisons were made between patients with and without thoracic LAP.
Results
Forty-eight patients were included. There were 30 patients (62.5%) with an ILD and 23 (48%) with at least one thoracic LAP on the first MDCT assessment. Median number per patient of thoracic LAP was 3 [1–8], with a mean size of 11.7 ± 1.7 mm, mainly located in right para-tracheal area (22.8% of the total number of LAP), right hilar area (20.3%), left hilar area (6.5%), and sub-carinal area (15.2%). PET-CT showed lymph node hypermetabolism in 11/15 patients (73.3%) with mean SUVmax at 4 ± 1.3. There were significantly more males (p = 0.002) and more patients exposed to silica (p = 0.001) in patients with thoracic LAP. ILD was significantly more extended according to Goh score (p = 0.03), and using semi-quantitative score for mixed ground-glass reticulation (p = 0.01) and global abnormalities (p = 0.03) in patients with thoracic LAP and ILD. Thirteen patients (27.1%) died during follow-up without significant difference according to the presence or not of thoracic LAP (p = 0.15). There was also no significant difference concerning immunosuppressive treatment initiation (p = 0.17).
Conclusions
Thoracic LAP are common in diffuse SSc and are generally multiple, not bulky, moderately hypermetabolic, and located at the base of the mediastinum lymph node chains. Their presence correlates with the extent of ILD. In absence of ILD, thoracic LAP presence seems to be often explained by silica exposure.
Trial Registration: NA.
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14
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Showalter K, Hoffmann A, Richardson C, Aaby D, Lee J, Dematte J, Agrawal R, Savas H, Wu X, Chang RW, Hinchcliff M. Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis. J Rheumatol 2021; 48:1830-1838. [PMID: 34266985 PMCID: PMC8985598 DOI: 10.3899/jrheum.210533] [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: 07/08/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To identify clinical factors, including esophageal dilation on chest high-resolution computed tomography (HRCT), that are associated with pulmonary function decline in patients with systemic sclerosis (SSc). METHODS Patients fulfilled 2013 SSc criteria and had ≥ 1 HRCT and ≥ 2 pulmonary function tests (PFTs). According to published methods, widest esophageal diameter (WED) and radiographic interstitial lung disease (ILD) were assessed, and WED was dichotomized as dilated (≥ 19 mm) vs not dilated (< 19 mm). Clinically meaningful PFT decline was defined as % predicted change in forced vital capacity (FVC) ≥ 5 and/or diffusion capacity for carbon monoxide (DLCO) ≥ 15. Linear mixed effects models were used to model PFT change over time. RESULTS One hundred thirty-eight patients with SSc met the study criteria: 100 (72%) had radiographic ILD; 49 (35%) demonstrated FVC decline (median follow-up 2.9 yrs). Patients with antitopoisomerase I (Scl-70) autoantibodies had 5-year FVC% predicted decline (-6.33, 95% CI -9.87 to -2.79), whereas patients without Scl-70 demonstrated 5-year FVC stability (+1.78, 95% CI -0.59 to 4.15). Esophageal diameter did not distinguish between those with vs without FVC decline. Patients with esophageal dilation had statistically significant 5-year DLCO% predicted decline (-5.58, 95% CI -10.00 to -1.15), but this decline was unlikely clinically significant. Similar results were observed in the subanalysis of patients with radiographic ILD. CONCLUSION In patients with SSc, Scl-70 positivity is a risk factor for FVC% predicted decline at 5 years. Esophageal dilation on HRCT was associated with a minimal, nonclinically significant decline in DLCO and no change in FVC during the 5-year follow-up. These results have prognostic implications for SSc-ILD patients with esophageal dilation.
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Affiliation(s)
- Kimberly Showalter
- K. Showalter, MD, Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, Illinois, and Hospital for Special Surgery, Department of Medicine, Division of Rheumatology, New York, New York
| | - Aileen Hoffmann
- A. Hoffmann, MS, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, Illinois
| | - Carrie Richardson
- C. Richardson, MD, Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, Illinois
| | - David Aaby
- D. Aaby, MS, Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, Chicago, Illinois
| | - Jungwha Lee
- J. Lee, PhD, MPH, Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, and Institute for Public Health and Medicine, Chicago, Illinois
| | - Jane Dematte
- J. Dematte, MD, MBA, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Chicago, Illinois
| | - Rishi Agrawal
- R. Agrawal, MD, H. Savas, MD, Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, Illinois
| | - Hatice Savas
- R. Agrawal, MD, H. Savas, MD, Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, Illinois
| | - Xiaoping Wu
- X. Wu, MD, MS, New York Presbyterian/Weill Cornell, Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York, New York
| | - Rowland W Chang
- R.W. Chang, MD, MPH, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Department of Preventive Medicine, and Institute for Public Health and Medicine, Chicago, Illinois
| | - Monique Hinchcliff
- M. Hinchcliff, MD, MS, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, Illinois, and Yale School of Medicine, Department of Medicine, Section of Rheumatology, Allergy & Immunology, New Haven, Connecticut, USA.
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15
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Copeland CR, Lancaster LH. Management of Progressive Fibrosing Interstitial Lung Diseases (PF-ILD). Front Med (Lausanne) 2021; 8:743977. [PMID: 34722582 PMCID: PMC8548364 DOI: 10.3389/fmed.2021.743977] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 09/09/2021] [Indexed: 11/13/2022] Open
Abstract
Progressive fibrosing interstitial lung diseases (PF-ILD) consist of a diverse group of interstitial lung diseases (ILD) characterized by a similar clinical phenotype of accelerated respiratory failure, frequent disease exacerbation and earlier mortality. Regardless of underlying disease process, PF-ILD progresses through similar mechanisms of self-sustained dysregulated cell repair, fibroblast proliferation and alveolar dysfunction that can be therapeutically targeted. Antifibrotic therapy with nintedanib or pirfenidone slow lung function decline and are the backbone of treatment for IPF with an expanded indication of PF-ILD for nintedanib. Immunosuppression is utilized for some subtypes of PF-ILD, including connective tissue disease ILD and hypersensitivity pneumonitis. Inhaled treprostinil is a novel therapy that improves exercise tolerance in individuals with PF-ILD and concomitant World Health Organization (WHO) group 3 pulmonary hypertension. Lung transplantation is the only curative therapy and can be considered in an appropriate and interested patient. Supportive care, oxygen therapy when appropriate, and treatment of comorbid conditions are important aspects of PF-ILD management. This review summarizes the current data and recommendations for management of PF-ILD.
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Affiliation(s)
- Carla R Copeland
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Lisa H Lancaster
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
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16
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Thoreau B, Chaigne B, Renaud A, Mouthon L. Treatment of systemic sclerosis. Presse Med 2021; 50:104088. [PMID: 34718109 DOI: 10.1016/j.lpm.2021.104088] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 10/20/2021] [Indexed: 12/29/2022] Open
Abstract
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.
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Affiliation(s)
- Benjamin Thoreau
- Institut Cochin, INSERM U1016, CNRS UMR 8104, Université de Paris; Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares d'Ile de France, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Benjamin Chaigne
- Institut Cochin, INSERM U1016, CNRS UMR 8104, Université de Paris; Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares d'Ile de France, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Arthur Renaud
- Institut Cochin, INSERM U1016, CNRS UMR 8104, Université de Paris; Service de Médecine Interne, Centre de Compétence Maladies Systémiques Autoimmunes Rares, CHU de Nantes, Nantes, France
| | - Luc Mouthon
- Institut Cochin, INSERM U1016, CNRS UMR 8104, Université de Paris; Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares d'Ile de France, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
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Kadakuntla A, Juneja A, Sattler S, Agarwal A, Panse D, Zakhary N, Pasumarthi A, Shapiro L, Tadros M. Dysphagia, reflux and related sequelae due to altered physiology in scleroderma. World J Gastroenterol 2021; 27:5201-5218. [PMID: 34497445 PMCID: PMC8384755 DOI: 10.3748/wjg.v27.i31.5201] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/13/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia. The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition, as well as by xerostomia. In the pharyngeal phase of swallowing, pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance. The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility. However, it can also be affected by obstruction from chronic reflux changes, pill-induced esophagitis, or Candida esophagitis. Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis. Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.
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Affiliation(s)
| | - Ankit Juneja
- Albany Medical College, Albany, NY 12208, United States
| | | | | | - Drishti Panse
- Albany Medical College, Albany, NY 12208, United States
| | - Nardin Zakhary
- Department of Dentistry, Ministry of Health, Alexandria 21500, Egypt
| | | | - Lee Shapiro
- Division of Rheumatology, Albany Medical Center, Albany, NY 12208, United States
| | - Micheal Tadros
- Division of Gastroenterology, Albany Medical Center, Albany, NY 12208, United States
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18
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Kadakuntla A, Juneja A, Sattler S, Agarwal A, Panse D, Zakhary N, Pasumarthi A, Shapiro L, Tadros M. Dysphagia, reflux and related sequelae due to altered physiology in scleroderma. World J Gastroenterol 2021; 27:5201-5218. [PMID: 34497445 DOI: 10.3748/wjg.v27.i31.5201.pmid:] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/13/2021] [Accepted: 07/30/2021] [Indexed: 01/30/2025] Open
Abstract
Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia. The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition, as well as by xerostomia. In the pharyngeal phase of swallowing, pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance. The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility. However, it can also be affected by obstruction from chronic reflux changes, pill-induced esophagitis, or Candida esophagitis. Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis. Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.
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Affiliation(s)
| | - Ankit Juneja
- Albany Medical College, Albany, NY 12208, United States
| | | | | | - Drishti Panse
- Albany Medical College, Albany, NY 12208, United States
| | - Nardin Zakhary
- Department of Dentistry, Ministry of Health, Alexandria 21500, Egypt
| | | | - Lee Shapiro
- Division of Rheumatology, Albany Medical Center, Albany, NY 12208, United States
| | - Micheal Tadros
- Division of Gastroenterology, Albany Medical Center, Albany, NY 12208, United States.
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19
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Luquez-Mindiola A, Atuesta AJ, Gómez-Aldana AJ. Gastrointestinal manifestations of systemic sclerosis: An updated review. World J Clin Cases 2021; 9:6201-6217. [PMID: 34434988 PMCID: PMC8362561 DOI: 10.12998/wjcc.v9.i22.6201] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/30/2021] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
Systemic sclerosis is an autoimmune disease characterized by vascular disease, fibrosis of the skin, and internal organ dysfunction. Gastrointestinal involvement is the most frequent complication of internal organs, impacting up to 90% of patients. Gastrointestinal involvement can affect any region of the gastrointestinal tract from the mouth to the anus, with a predominance of disorders being observed at the level of the upper digestive tract. The gastrointestinal involvement primarily involves the esophagus, small bowel, and rectum. The severity of gastrointestinal involvement affects quality of life and is a marker of worse prognosis and mortality in these patients. In this review, we describe the current findings regarding gastrointestinal involvement by this entity.
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Affiliation(s)
| | - Alexis Javier Atuesta
- Department of Internal Medicine, Universidad Nacional de Colombia, Bogota 11711, Colombia
| | - Andres Jose Gómez-Aldana
- Department of Endoscopy, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 11711, Colombia
- Faculty of Medicine, Universidad de los Andes, Bogota 11711, Colombia
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20
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Kapnadak SG, Raghu G. Lung transplantation for interstitial lung disease. Eur Respir Rev 2021; 30:30/161/210017. [PMID: 34348979 DOI: 10.1183/16000617.0017-2021] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 04/02/2021] [Indexed: 01/18/2023] Open
Abstract
Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide. Several unique features in patients with ILD can impact optimal timing of referral or listing for LTx, pre- or post-transplant risks, candidacy and post-transplant management. As the epidemiology of LTx and community practices have evolved, recent literature describes outcomes and approaches in higher-risk candidates. In this review, we discuss the unique and important clinical findings, course, monitoring and management of patients with IPF and other progressive fibrotic ILDs during pre-LTx evaluation and up to the day of transplantation; the need for co-management with clinical experts in ILD and LTx is emphasised. Some post-LTx complications are unique in these patient cohorts, which require prompt detection and appropriate management by experts in multiple disciplines familiar with telomere biology disorders and infectious, haematological, oncological and cardiac complications to enhance the likelihood of improved outcomes and survival of LTx recipients with IPF and other ILDs.
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Affiliation(s)
- Siddhartha G Kapnadak
- Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Washington, Seattle, WA, USA
| | - Ganesh Raghu
- Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Washington, Seattle, WA, USA .,Dept of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
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21
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Voulgaris TA, Karamanolis GP. Esophageal manifestation in patients with scleroderma. World J Clin Cases 2021; 9:5408-5419. [PMID: 34307594 PMCID: PMC8281422 DOI: 10.12998/wjcc.v9.i20.5408] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/22/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis (SSc). Esophageal involvement may lead to a significant reduction in patient quality of life. The exact pathophysiology is complex and not yet fully elucidated. Ultimately, esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus. Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility. Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease. No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc, though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc. Further exploration can be made by high resolution manometry and pH-impedance study. Proton pump inhibitors remain the mainstay of treatment, while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances. Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage, and new therapeutic modalities are emerging. The role of surgical treatment is restricted and should only be preserved for resistant cases.
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Affiliation(s)
- Theodoros A Voulgaris
- Department of Gastroenterology and Hepatology, Laiko General Hospital, National and Kapodistian University of Athens, Athens 11527, Greece
| | - Georgios P Karamanolis
- Department of Gastroenterology and Hepatology, Laiko General Hospital, National and Kapodistian University of Athens, Athens 11527, Greece
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22
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Delaney FT, Fenlon HM, Buckley B, Welaratne I, Cronin CG. Multimodality imaging of the gastrointestinal manifestations of scleroderma. Clin Radiol 2021; 76:640-649. [PMID: 34108098 DOI: 10.1016/j.crad.2021.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 04/21/2021] [Indexed: 11/29/2022]
Abstract
Scleroderma is a complex multisystem connective tissue disorder. Early visceral disease, such as gastrointestinal (GI) involvement, is associated with significant morbidity and a poorer prognosis. Prompt diagnosis is crucial to allow disease modifying therapies be initiated early in the course of the disease. The primary underlying pathophysiology in the GI tract is dysmotility, muscular atrophy, and fibrosis, and this is reflected in the imaging features. In this paper, we demonstrate the imaging appearances of involvement of the GI tract and describe the use of advanced imaging with magnetic resonance enterography (MRE). A multimodal imaging approach is required to identify both characteristic features of scleroderma and potential complications. Traditional fluoroscopic contrast (barium) studies are still commonly performed for assessment of the oesophagus. More recent advances in cross-sectional imaging allow for thorough three-dimensional assessment of the entire GI tract. MRE is particularly useful for small bowel evaluation while also allowing "pseudodynamic" functional imaging and concomitant assessment of the other abdominal viscera and structures.
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Affiliation(s)
- F T Delaney
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland.
| | - H M Fenlon
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| | - B Buckley
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| | - I Welaratne
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| | - C G Cronin
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
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23
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Hurtubise R, Hudson M, Gyger G, Wang M, Steele RJ, Baron M, Hoa S. Association between gastroprotective agents and risk of incident interstitial lung disease in systemic sclerosis. Respir Med 2021; 185:106482. [PMID: 34089970 DOI: 10.1016/j.rmed.2021.106482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/14/2021] [Accepted: 05/20/2021] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Although interstitial lung disease (ILD) occurs in over half of systemic sclerosis (SSc) patients and represents a leading cause of mortality, there are currently no preventative strategies. We evaluated if gastroprotective agents were associated with a lower incident risk of SSc-ILD. METHODS An SSc cohort without clinically apparent ILD at baseline was constructed from the Canadian Scleroderma Research Group registry. The primary exposure was any use of gastroprotective agents. Treatment with promotility agents was assessed as a secondary exposure. Time to development of clinically apparent ILD was compared between exposed and unexposed person-time, using a multivariable marginal structural Cox model incorporating inverse probability of treatment weights to address time-varying confounding. RESULTS In total, 798 subjects met inclusion criteria. At cohort entry, median disease duration was 7.6 (IQR 3.9-15.6) years. During a median 4.4 (IQR 2.6-7.2) years of follow-up, 158 new ILD cases were diagnosed, for a crude incidence of 4.4 (95% CI 3.8-5.1) events per 100 person-years. Most (2085, 73.4%) person-visits were exposed to gastroprotective agents, 579 (20.4%) were exposed to promotility agents, and 554 (19.5%) were exposed to both agents. The marginal structural weighted hazard ratio (HR) for incident ILD related to gastroprotective agents was 0.86 (95% CI 0.52-1.41). When exposure was defined as treatment with promotility agents, the weighted adjusted HR was 0.79 (95% CI: 0.35-1.77). CONCLUSION In this large retrospective cohort study, we were unable to demonstrate a protective role for gastroprotective and promotility agents in preventing clinically apparent SSc-ILD.
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Affiliation(s)
- Raphaël Hurtubise
- Department of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Marie Hudson
- Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada; Lady Davis Institute of Medical Research, Montreal, Quebec, Canada
| | - Geneviève Gyger
- Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada
| | - Mianbo Wang
- Lady Davis Institute of Medical Research, Montreal, Quebec, Canada
| | - Russell J Steele
- Department of Mathematics and Statistics, McGill University, Montreal, Quebec, Canada
| | - Murray Baron
- Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada; Lady Davis Institute of Medical Research, Montreal, Quebec, Canada
| | - Sabrina Hoa
- Department of Medicine, Université de Montréal, Montreal, Quebec, Canada; Division of Rheumatology, Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
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Ma L, Zhu Q, Zhang Y, Li J, Jiang Y, Xu D, Zeng X, Hou Y, Liu H. Esophagus involvement in systemic sclerosis: ultrasound parameters and association with clinical manifestations. Arthritis Res Ther 2021; 23:122. [PMID: 33882993 PMCID: PMC8059267 DOI: 10.1186/s13075-021-02505-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 04/06/2021] [Indexed: 11/16/2022] Open
Abstract
Background The esophagus involvement in systemic sclerosis (SSc) is very common yet underestimated due to the lack of suitable screening tools. This study aims to explore the usefulness of ultrasound (US) in the assessment of esophagus involvement and to identify its relationship with clinical and CT manifestations. Methods We performed transabdominal esophageal US in 38 SSc patients and 38 controls. US parameters including the abdominal esophagus length, esophagus wall thickness, shear-wave elastography, gastro-esophageal (His) angle, and reflux were compared. Relationships between distinguishable US parameters and clinical/CT parameters, such as gastro-esophageal reflux disease questionnaire (GERDQ), modified Rodnan skin score (mRSS), interstitial lung disease (ILD) score, the largest esophagus diameter (Dmax), and esophagus dilation percentage (%Eop), were evaluated. Results Abdominal esophagus length was shorter in the SSc group than the control group (2.69 cm vs 3.06 cm, P = 0.018), whereas His angle and the angle change before and after drinking water were larger in the SSc group than the control group (121° vs 108°, P < 0.001; 7.97° vs 2.92°, P = 0.025). Reflux was more frequently seen in the SSc group than the control group (7/38 vs 0/38; P = 0.017). As for correlation with clinical and CT parameters, His angle was higher in patients with GERDQ ≥ 8 than GERDQ < 8 (116.5° vs 125.6°, P = 0.035). Patients with reflux showed higher ILD score than patients without (15.8 vs 9.6, P = 0.043). Furthermore, abdominal esophagus length was negatively correlated with %Eop and Dmax (r = − 0.573, P < 0.001; r = − 0.476, P = 0.003). Conclusion US parameters of the esophagus can distinguish SSc patients from controls, as well as have correlations with clinical and CT characteristics. Our pilot study first shows that US can be used as a noninvasive and convenient method to evaluate the esophagus involvement in SSc.
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Affiliation(s)
- Li Ma
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Qingli Zhu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yan Zhang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Jianchu Li
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yong Hou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.
| | - He Liu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.
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25
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Jee AS, Sheehy R, Hopkins P, Corte TJ, Grainge C, Troy LK, Symons K, Spencer LM, Reynolds PN, Chapman S, de Boer S, Reddy T, Holland AE, Chambers DC, Glaspole IN, Jo HE, Bleasel JF, Wrobel JP, Dowman L, Parker MJS, Wilsher ML, Goh NSL, Moodley Y, Keir GJ. Diagnosis and management of connective tissue disease-associated interstitial lung disease in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand. Respirology 2020; 26:23-51. [PMID: 33233015 PMCID: PMC7894187 DOI: 10.1111/resp.13977] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 09/26/2020] [Accepted: 10/22/2020] [Indexed: 12/12/2022]
Abstract
Pulmonary complications in CTD are common and can involve the interstitium, airways, pleura and pulmonary vasculature. ILD can occur in all CTD (CTD-ILD), and may vary from limited, non-progressive lung involvement, to fulminant, life-threatening disease. Given the potential for major adverse outcomes in CTD-ILD, accurate diagnosis, assessment and careful consideration of therapeutic intervention are a priority. Limited data are available to guide management decisions in CTD-ILD. Autoimmune-mediated pulmonary inflammation is considered a key pathobiological pathway in these disorders, and immunosuppressive therapy is generally regarded the cornerstone of treatment for severe and/or progressive CTD-ILD. However, the natural history of CTD-ILD in individual patients can be difficult to predict, and deciding who to treat, when and with what agent can be challenging. Establishing realistic therapeutic goals from both the patient and clinician perspective requires considerable expertise. The document aims to provide a framework for clinicians to aid in the assessment and management of ILD in the major CTD. A suggested approach to diagnosis and monitoring of CTD-ILD and, where available, evidence-based, disease-specific approaches to treatment have been provided.
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Affiliation(s)
- Adelle S Jee
- Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, University of Sydney, Sydney, NSW, Australia.,NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia
| | - Robert Sheehy
- Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane, QLD, Australia.,School of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Peter Hopkins
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,School of Medicine, University of Queensland, Brisbane, QLD, Australia.,Queensland Lung Transplant service, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Tamera J Corte
- Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, University of Sydney, Sydney, NSW, Australia.,NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia
| | - Christopher Grainge
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Department of Respiratory Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Lauren K Troy
- Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, University of Sydney, Sydney, NSW, Australia
| | - Karen Symons
- Department of Respiratory Medicine, Alfred Hospital, Melbourne, VIC, Australia
| | - Lissa M Spencer
- Department of Physiotherapy, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Paul N Reynolds
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia.,Lung Research Laboratory, University of Adelaide, Adelaide, SA, Australia
| | - Sally Chapman
- Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Sally de Boer
- Respiratory Services, Auckland District Health Board, Auckland, New Zealand
| | - Taryn Reddy
- Department of Medical Imaging, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Anne E Holland
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Department of Allergy, Immunology and Respiratory Medicine, Monash University, Melbourne, VIC, Australia.,Department of Physiotherapy, Alfred Health, Melbourne, VIC, Australia.,Institute for Breathing and Sleep, Melbourne, VIC, Australia
| | - Daniel C Chambers
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,School of Medicine, University of Queensland, Brisbane, QLD, Australia.,Queensland Lung Transplant service, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Ian N Glaspole
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Department of Respiratory Medicine, Alfred Hospital, Melbourne, VIC, Australia.,Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Helen E Jo
- Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, University of Sydney, Sydney, NSW, Australia.,NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia
| | - Jane F Bleasel
- Central Clinical School, University of Sydney, Sydney, NSW, Australia.,Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Jeremy P Wrobel
- Advanced Lung Disease Unit, Fiona Stanley Hospital, Perth, WA, Australia.,Department of Medicine, University of Notre Dame Australia, Fremantle, WA, Australia
| | - Leona Dowman
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Department of Allergy, Immunology and Respiratory Medicine, Monash University, Melbourne, VIC, Australia.,Physiotherapy Department, Austin Health, Melbourne, VIC, Australia
| | - Matthew J S Parker
- Central Clinical School, University of Sydney, Sydney, NSW, Australia.,NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Margaret L Wilsher
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,Respiratory Services, Auckland District Health Board, Auckland, New Zealand.,Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Nicole S L Goh
- Department of Respiratory Medicine, Alfred Hospital, Melbourne, VIC, Australia.,Institute for Breathing and Sleep, Melbourne, VIC, Australia.,Department of Respiratory Medicine, Austin Hospital, Melbourne, VIC, Australia.,Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia
| | - Yuben Moodley
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Sydney, NSW, Australia.,University of Western Australia, Institute for Respiratory Health, Perth, WA, Australia.,Department of Respiratory Medicine, Fiona Stanley Hospital, Perth, WA, Australia
| | - Gregory J Keir
- Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane, QLD, Australia.,School of Medicine, University of Queensland, Brisbane, QLD, Australia
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26
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Worsening of esophageal dilatation is associated with increase in a high-resolution computed tomography (HRCT) score in early systemic sclerosis-associated interstitial lung disease (SSc-ILD). Clin Rheumatol 2020; 40:955-963. [PMID: 32803568 DOI: 10.1007/s10067-020-05346-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 08/05/2020] [Accepted: 08/11/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Data regarding longitudinal association between changes (Δ: time2-time1) in the widest esophageal diameter (WED) and Δ HRCT score in early SSc-ILD patients is limited. We therefore investigated the association of ΔWED with Δ HRCT score and predictors of a worse Δ HRCT score in those patients. METHODS We used an inception cohort of early SSc-ILD patients with availability for two HRCT records at enrollment and 1-year follow-up.The extent of ground glass, reticulation, bronchiectasis, and honeycombing was scored and then aggregated to produce a total HRCT score. The WED was measured at four levels and the maximum value was used. The Δ maximum WED, Δ mean WED, and Δ tHRCT score were analyzed. RESULTS We recruited 75 early SSc-ILD patients and found a significant correlation of Δ tHRCT score with a Δ maximum WED (rho = 0.34, p < 0.01) and Δ mean WED (rho = 0.26, p < 0.05). There were 34 patients with a worsening Δ tHRCT (Δ > 0), 17 with stability (Δ = 0), and 24 with improvement (Δ < 0). Patients with a worsening ILD had a significantly shorter disease duration, lower prevalence of tendon friction rub, higher cumulative prednisolone dose, and larger ΔWED than those with stable and improved Δ tHRCT scores. Multivariate ordinal logistic regression identified a larger Δ mean WED (OR 1.21, 95% CI 1.03-1.42, p = 0.02) as a predictor of worsening HRCT score, while presence of tendon friction rub was associated with a lower risk (OR 0.18, 95% CI 0.04-0.77, p = 0.021). CONCLUSION Our study cohort found that a worsening esophageal diameter was a predictor of progression of lung fibrosis determined by HRCT score in early SSc-ILD. A further study regarding esophageal dilation progression different in early versus longstanding SSc-ILD is needed. Key Points •In early SSc-ILD patients, we demonstrated that a worsening esophageal diameter was a predictor of progression of HRCT score at 1-year follow-up. •Further study regarding the association of worsening of the esophageal dilatation with the progression of ILD comparing between early versus late SSc-ILD is needed.
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27
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Connective Tissue Disease-Related Interstitial Lung Disease: Prevalence, Patterns, Predictors, Prognosis, and Treatment. Lung 2020; 198:735-759. [DOI: 10.1007/s00408-020-00383-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/26/2020] [Indexed: 12/13/2022]
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Nihtyanova SI, Denton CP. Pathogenesis of systemic sclerosis associated interstitial lung disease. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2020; 5:6-16. [PMID: 35382227 PMCID: PMC8922569 DOI: 10.1177/2397198320903867] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 12/24/2019] [Indexed: 12/12/2022]
Abstract
Systemic sclerosis is an autoimmune disease leading to vasculopathy and fibrosis
of skin and internal organs. Despite likely shared pathogenic mechanisms, the
patterns of skin and lung fibrosis differ. Pathogenesis of interstitial lung
disease, a major cause of death in systemic sclerosis, reflects the intrinsic
disease pathobiology and is associated with distinct clinical phenotypes and
laboratory characteristics. The commonest histological pattern of systemic
sclerosis–interstitial lung disease is non-specific interstitial pneumonia.
Systemic sclerosis–interstitial lung disease pathogenesis involves multiple
components, including susceptibility and triggering factors, which could be
genetic or environmental. The process is amplified likely through ongoing
inflammation and the link between inflammatory activity and fibrosis with IL6
emerging as a key mediator. The disease is driven by epithelial injury,
reflected by markers in the serum, such as surfactant proteins and KL-6. In
addition, mediators that are produced by epithelial cells and that regulate
inflammatory cell trafficking may be important, especially CCL2. Other factors,
such as CXCL4 and CCL18, point towards immune-mediated damage or injury
response. Monocytes and alternatively activated macrophages appear to be
important. Transforming growth factor beta appears central to pathogenesis and
regulates epithelial repair and fibroblast activation. Understanding
pathogenesis may help to unravel the stages of systemic sclerosis–interstitial
lung disease, risks of progression and determinants of outcome. With this
article, we set out to review the multiple factors, including genetic,
environmental, cellular and molecular, that may be involved in the pathogenesis
of systemic sclerosis–interstitial lung disease and the mechanisms leading to
sustained fibrosis. We propose a model for the pathogenesis of systemic
sclerosis–interstitial lung disease, based on the available literature.
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Affiliation(s)
- Svetlana I Nihtyanova
- Centre for Rheumatology and Connective Tissue Diseases, University College London, London, UK
| | - Christopher P Denton
- Centre for Rheumatology and Connective Tissue Diseases, University College London, London, UK
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Response to the letter by Dr. Costa-Moreira, Dr. Peixoto, Dr. Ramalho, and Dr. Macedo regarding our manuscript: "Relationship between esophageal motility abnormalities and skin or lung involvements in patients with systemic sclerosis". J Gastroenterol 2020; 55:246-247. [PMID: 31549241 DOI: 10.1007/s00535-019-01630-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 09/11/2019] [Indexed: 02/04/2023]
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Hoffmann-Vold AM, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, Bruni C, Carducci P, Carreira PE, Castellví I, Del Galdo F, Distler JHW, Foeldvari I, Fraticelli P, George PM, Griffiths B, Guillén-Del-Castillo A, Hamid AM, Horváth R, Hughes M, Kreuter M, Moazedi-Fuerst F, Olas J, Paul S, Rotondo C, Rubio-Rivas M, Seferian A, Tomčík M, Uzunhan Y, Walker UA, Więsik-Szewczyk E, Distler O. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. THE LANCET. RHEUMATOLOGY 2020; 2:e71-e83. [PMID: 38263663 DOI: 10.1016/s2665-9913(19)30144-4] [Citation(s) in RCA: 171] [Impact Index Per Article: 34.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 12/05/2019] [Accepted: 12/06/2019] [Indexed: 11/18/2022]
Abstract
BACKGROUND Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. METHODS Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. FINDINGS Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. INTERPRETATION Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. FUNDING An unrestricted grant from Boehringer Ingelheim International.
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Affiliation(s)
| | - Toby M Maher
- National Heart and Lung Institute, Imperial College London, London, UK; Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
| | | | - Ali Ashrafzadeh
- Rheumatology Center of Excellence, IQVIA, San Diego, CA, USA
| | - Rafic Barake
- Department of Pulmonary Diseases, Centre Hospitalier de Rambouillet, Rambouillet, France
| | | | - Cosimo Bruni
- Department of Rheumatology/Scleroderma Unit, University of Florence, Florence, Italy
| | - Paolo Carducci
- Pulmonology Unit, San Salvatore Hospital, L'Aquila, Italy
| | | | - Ivan Castellví
- Department of Rheumatology, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Francesco Del Galdo
- NIHR Biomedical Research Centre and Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Jörg H W Distler
- Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Ivan Foeldvari
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Hamburg, Germany
| | - Paolo Fraticelli
- Department of Internal Medicine, Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Peter M George
- National Heart and Lung Institute, Imperial College London, London, UK; Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
| | - Bridget Griffiths
- Department of Rheumatology, Freeman Hospital, Newcastle-upon-Tyne, UK
| | | | - Abdul Monem Hamid
- Department of Pneumology and Lung Transplantation, Foch Hospital, Paris, France; Collège de Médecine des Hôpitaux de Paris, Paris, France
| | - Rudolf Horváth
- Department of Paediatric and Adult Rheumatology, Faculty Hospital Motol, Prague, Czech Republic
| | - Michael Hughes
- Department of Rheumatology, Royal Hallamshire Hospital, Sheffield, UK
| | - Michael Kreuter
- Center for Interstitial and Rare Lung Diseases, Pneumology Thoraxklinik Heidelberg University Hospital, Heidelberg and German Center for Lung Research, Germany
| | - Florentine Moazedi-Fuerst
- Department of Internal Medicine, Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria
| | - Jacek Olas
- Scleroderma Outpatient Clinic, Małopolska Center of Rheumatology, Immunology and Rehabilitation, Krakow, Poland
| | - Suman Paul
- Respiratory Medicine Department, Royal Preston Hospital, Preston, UK
| | - Cinzia Rotondo
- Scleroderma Outpatient Clinic, Rheumatology Unit, University Hospital Ospedali Riuniti di Foggia, Foggia, Italy
| | - Manuel Rubio-Rivas
- Department of Internal Medicine, Bellvitge University Hospital, Barcelona, Spain
| | - Andrei Seferian
- University Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | | | - Yurdagül Uzunhan
- Assistance Publique-Hôpitaux de Paris, Avicenne Hospital, Pneumology Department, INSERM UMR 1272, Paris 13 University, Bobigny, France
| | - Ulrich A Walker
- Department of Rheumatology, University Hospital Basel, Basel, Switzerland
| | - Ewa Więsik-Szewczyk
- Department of Internal Medicine, Pneumonology, Allergology and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, Warsaw, Poland
| | - Oliver Distler
- Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
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Tezcan D, Turan Ç, Yılmaz S, Sivrikaya A, Gülcemal S, Limon M, Ecer B. What do simple hematological parameters tell us in patients with systemic sclerosis? ACTA DERMATOVENEROLOGICA ALPINA PANNONICA ET ADRIATICA 2020. [DOI: 10.15570/actaapa.2020.23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Fischer A, Patel NM, Volkmann ER. Interstitial Lung Disease in Systemic Sclerosis: Focus on Early Detection and Intervention. Open Access Rheumatol 2019; 11:283-307. [PMID: 31849543 PMCID: PMC6910104 DOI: 10.2147/oarrr.s226695] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 11/09/2019] [Indexed: 12/11/2022] Open
Abstract
Systemic sclerosis (SSc) is a progressive and often devastating disease characterized by autoimmune dysfunction, vasculopathy, and fibrosis. Interstitial lung disease (ILD) is identified in the majority of patients with SSc and is the leading cause of SSc-related mortality. Although clinical manifestations and ILD severity vary among patients, lung function typically declines to the greatest extent during the first 3-4 years after disease onset. We aim to provide an overview of SSc-associated ILD (SSc-ILD) with a focus on current and emerging tools for early diagnosis of ILD and current and novel treatments under investigation. Early detection of ILD provides the opportunity for early therapeutic intervention, which could improve patient outcomes. Thoracic high-resolution computed tomography is the most effective method of identifying ILD in patients with SSc; it enables detection of mild lung abnormalities and plays an important role in monitoring disease progression. Cyclophosphamide and mycophenolate mofetil are the most commonly prescribed treatments for SSc-ILD. Recently, nintedanib (an antifibrotic) was approved by the Food and Drug Administration for patients with SSc-ILD; it is indicated for slowing the rate of decline in pulmonary function. However, there is a need for additional effective and well-tolerated disease-modifying therapy. Ongoing studies are evaluating other antifibrotics and novel agents. We envision that early detection of lung involvement, combined with the emergence and integration of novel therapies, will lead to improved outcomes in patients with SSc-ILD.
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Affiliation(s)
- Aryeh Fischer
- Division of Rheumatology, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, CO, USA
| | - Nina M Patel
- Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Elizabeth R Volkmann
- Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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Ambartsumyan L, Zheng HB, Iyer RS, Soares J, Henstorf G, Stevens AM. Relationship Between Esophageal Abnormalities on Fluoroscopic Esophagram and Pulmonary Function Testing in Juvenile Systemic Sclerosis. Arthritis Care Res (Hoboken) 2019; 71:1444-1449. [DOI: 10.1002/acr.23778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 09/25/2018] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Ramesh S. Iyer
- Seattle Children's HospitalUniversity of Washington Seattle
| | | | | | - Anne M. Stevens
- Seattle Children's HospitalUniversity of Washington, and Seattle Children's Research Institute Seattle Washington
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Lakota K, Hanumanthu VS, Agrawal R, Carns M, Armanios M, Varga J. Short lymphocyte, but not granulocyte, telomere length in a subset of patients with systemic sclerosis. Ann Rheum Dis 2019; 78:1142-1144. [PMID: 30679155 DOI: 10.1136/annrheumdis-2018-214499] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 12/03/2018] [Accepted: 12/29/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Katja Lakota
- Division of Rheumatology, Northwestern Scleroderma Program, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
- Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of Biodiversity, Faculty of Mathematics, Natural Science and Information Technology, University of Primorska, Koper, Slovenia
| | - Vidya Sagar Hanumanthu
- Department of Oncology and Telomere Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Rishi Agrawal
- Department of Radiology, Northwestern University, Chicago, Illinois, USA
| | - Mary Carns
- Division of Rheumatology, Northwestern Scleroderma Program, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Mary Armanios
- Department of Oncology and Telomere Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - John Varga
- Division of Rheumatology, Northwestern Scleroderma Program, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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Tétreault MP, Kahrilas P. GI Manifestations With a Focus on the Esophagus: Recent Progress in Understanding Pathogenesis. Curr Rheumatol Rep 2019; 21:42. [PMID: 31270707 DOI: 10.1007/s11926-019-0841-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE OF REVIEW Esophageal dysfunction is common in systemic sclerosis (SSc) patients. Limited treatment options are available for scleroderma esophageal disease. Here, we discuss recent updates on the diagnosis, treatment, and characterization that have been made in patients with scleroderma esophageal disease. RECENT FINDINGS In the past few years, novel diagnostic tools have provided insight into esophageal dysmotility in SSc patients. New drugs are being tested and might improve symptoms and quality of life in SSc patients with esophageal dysfunction. Molecular stratification methods have facilitated the identification of molecular signatures in the esophagus of SSc patients. The Friend leukemia integration 1 (Fli1) conditional knockout mouse is the first animal model to report an esophageal phenotype with SSc features. The clinical presentation in SSc patients with esophageal dysfunction is heterogeneous, complicating diagnosis and management. The improvement of diagnostic tools for esophageal symptoms and dysfunction and the use of molecular approaches in SSc mouse models and patient biopsies offer an opportunity to improve the characterization of SSc esophageal disease, which should help improve management and treatment decisions.
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Affiliation(s)
- Marie-Pier Tétreault
- Department of Medicine, Gastroenterology and Hepatology Division, Northwestern University Feinberg School of Medicine, 15-753 Tarry Building, 300 East Superior Street, Chicago, IL, 60611-3010, USA.
| | - Peter Kahrilas
- Department of Medicine, Gastroenterology and Hepatology Division, Northwestern University Feinberg School of Medicine, 15-753 Tarry Building, 300 East Superior Street, Chicago, IL, 60611-3010, 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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Chwiesko A, Kowal-Bielecka O, Sierakowski S. Perspectives on the interlinked nature of systemic sclerosis and reflux disease. Expert Rev Gastroenterol Hepatol 2019; 13:213-227. [PMID: 30791766 DOI: 10.1080/17474124.2019.1561274] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Systemic sclerosis (SSc) is a multisystem connective tissue disease, characterized by chronic inflammation and vascular changes that result in esophageal smooth muscle atrophy and fibrosis. Subsequent progressive loss of peristalsis in the distal esophagus and loss of lower esophageal sphincter function lead to problems with the protective barrier and exposure of sensitive tissues to the gastroduodenal contents, a disorder called reflux disease. Areas covered: Depending on the range, nature and symptoms of the disease, the term 'reflux disease' may refer to gastroesophageal reflux, laryngopharyngeal reflux, microaspiration into the airways and silent reflux. Despite the links between these visceral complications, this connection remains controversial. This is due to a lack of complete understanding, the asymptomatic nature of the disease and the limited diagnostic accuracy of tests, which can delay diagnosis. Such delays are problematic, given that the early detection of GERD in SSc patients, the timing of assessment, the treatment of the organs involved are critical aspects of patient prognosis and disease outcome. Expert commentary: This review summarizes the most recent knowledge about the pathophysiology, diagnosis and prospective treatment of GERD in SSc patients and highlights how innovative technologies applied through an integrative, interdisciplinary approach may soon lead to effective treatment strategies.
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Affiliation(s)
- Adam Chwiesko
- a Department of Gastroenterology and Internal Medicine , Medical University of Bialystok , Bialystok , Poland
| | - Otylia Kowal-Bielecka
- b Department of Rheumatology and Internal Medicine , Medical University of Bialystok , Bialystok , Poland
| | - Stanislaw Sierakowski
- b Department of Rheumatology and Internal Medicine , Medical University of Bialystok , Bialystok , Poland
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Denton CP, Wells AU, Coghlan JG. Major lung complications of systemic sclerosis. Nat Rev Rheumatol 2018; 14:511-527. [DOI: 10.1038/s41584-018-0062-0] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Silva BRA, Rodrigues RS, Rufino R, Costa CH, Vilela VS, Levy RA, Guimarães ARM, Carvalho ARS, Lopes AJ. Computed tomography trachea volumetry in patients with scleroderma: Association with clinical and functional findings. PLoS One 2018; 13:e0200754. [PMID: 30067820 PMCID: PMC6070209 DOI: 10.1371/journal.pone.0200754] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 07/01/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND In scleroderma, excessive collagen production can alter tracheal geometry, and computed tomography (CT) volumetry of this structure may aid in detecting possible abnormalities. The objectives of this study were to quantify the morphological abnormalities in the tracheas of patients with scleroderma and to correlate these findings with data on clinical and pulmonary function. METHODS This was a cross-sectional study in which 28 adults with scleroderma and 27 controls matched by age, gender and body mass index underwent chest CT with posterior segmentation and skeletonization of the images. In addition, all participants underwent pulmonary function tests and clinical evaluation, including the modified Rodnan skin score (mRSS). RESULTS Most patients (71.4%) had interstitial lung disease on CT. Compared to controls, patients with scleroderma showed higher values in the parameters measured by CT trachea volumetry, including area, eccentricity, major diameter, minor diameter, and tortuosity. The tracheal area and equivalent diameter were negatively correlated with the ratio between forced expiratory flow and forced inspiratory flow at 50% of forced vital capacity (FEF50%/FIF50%) (r = -0.44, p = 0.03 and r = -0.46, p = 0.02, respectively). The tracheal tortuosity was negatively correlated with peak expiratory flow (r = -0.51, p = 0.008). The mRSS showed a positive correlation with eccentricity (r = 0.62, p < 0.001) and tracheal tortuosity (r = 0.51, p = 0.007), while the presence of anti-topoisomerase I antibody (ATA) showed a positive correlation with tracheal tortuosity (r = 0.45, p = 0.03). CONCLUSIONS In a sample composed predominantly of scleroderma patients with associated interstitial lung disease, there were abnormalities in tracheal geometry, including greater eccentricity, diameter and tortuosity. In these patients, abnormalities in the geometry of the trachea were associated with functional markers of obstruction. In addition, tracheal tortuosity was correlated with cutaneous involvement and the presence of ATA.
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Affiliation(s)
- Bruno Rangel Antunes Silva
- Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Rogério Rufino
- Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Cláudia Henrique Costa
- Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Veronica Silva Vilela
- Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Roger Abramino Levy
- Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Alan Ranieri Medeiros Guimarães
- Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Alysson Roncally Silva Carvalho
- Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Laboratory of Pulmonary Engineering, Biomedical Engineering Programme, Alberto Luiz Coimbra Institute of Post-Graduation and Research in Engineering, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Agnaldo José Lopes
- Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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Panopoulos S, Bournia VK, Konstantonis G, Fragiadaki K, Sfikakis PP, Tektonidou MG. Predictors of morbidity and mortality in early systemic sclerosis: Long-term follow-up data from a single-centre inception cohort. Autoimmun Rev 2018; 17:816-820. [DOI: 10.1016/j.autrev.2018.02.008] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 02/22/2018] [Indexed: 11/26/2022]
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Abstract
Although classification criteria for systemic sclerosis (SSc) do not incorporate gastrointestinal tract (GIT) manifestations often present in this disease, the GIT is the most common internal organ involved. Pathophysiology of GIT involvement is thought to be similar to other organs in SSc with fibroproliferative vascular lesions of small arteries and arterioles, increased production of profibrotic growth factors, and alterations of innate, humoral, and cellular immunity. These processes result in neuropathy progressing to myopathy with eventual fibrosis. Proper diagnostics and therapeutics for SSc-GIT involvement require the treating physician to have an understanding of an integrated approach and potential medication adverse effects.
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Affiliation(s)
- Tracy M Frech
- Department of Internal Medicine, Division of Rheumatology, University of Utah, Salt Lake Veterans Affair Medical Center, Salt Lake City, UT, USA.
| | - Diane Mar
- Department of Internal Medicine, University of Colorado, Denver, 12631 East 17th Avenue, Aurora, CO 80045, USA
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Strek ME. Systemic sclerosis-associated interstitial lung disease: Role of the oesophagus in outcomes. Respirology 2018; 23:885-886. [PMID: 29890565 DOI: 10.1111/resp.13335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Accepted: 05/24/2018] [Indexed: 12/22/2022]
Affiliation(s)
- Mary E Strek
- Section of Pulmonary and Critical Care Medicine, University of Chicago Medical Center, Chicago, IL, USA
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Akiyama J, Kuribayashi S, Baeg MK, Bortoli N, Valitova E, Savarino EV, Kusano M, Triadafilopoulos G. Current and future perspectives in the management of gastroesophageal reflux disease. Ann N Y Acad Sci 2018; 1434:70-83. [PMID: 29766521 DOI: 10.1111/nyas.13850] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 03/28/2018] [Accepted: 04/06/2018] [Indexed: 12/12/2022]
Affiliation(s)
- Junichi Akiyama
- Division of Gastroenterology and HepatologyNational Center for Global Health and Medicine Tokyo Japan
| | - Shiko Kuribayashi
- Division of Gastroenterology and Hepatology, Integrative Center of Internal MedicineGunma University Hospital Maebashi Japan
| | - Myong Ki Baeg
- Division of Gastroenterology, Department of Internal MedicineCatholic Kwandong University College of Medicine, International St. Mary's Hospital Incheon South Korea
| | - Nicola Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of Pisa Pisa Italy
| | - Elen Valitova
- Department of Upper Gastrointestinal Tract DisordersClinical Scientific Centre Moscow Russia
| | - Edoardo V. Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and GastroenterologyUniversity of Padua Padua Italy
| | - Motoyasu Kusano
- Division of Gastroenterology and Hepatology, Integrative Center of Internal MedicineGunma University Hospital Maebashi Japan
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Lung Involvements in Rheumatic Diseases: Update on the Epidemiology, Pathogenesis, Clinical Features, and Treatment. BIOMED RESEARCH INTERNATIONAL 2018; 2018:6930297. [PMID: 29854780 PMCID: PMC5964428 DOI: 10.1155/2018/6930297] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 03/27/2018] [Indexed: 01/25/2023]
Abstract
Lung illness encountered in patients with rheumatic diseases bears clinical significance in terms of increased morbidity and mortality as well as potential challenges placed on patient care. Although our understanding of natural history of this important illness is still limited, epidemiologic knowledge has been accumulated during the past decade to provide useful information on the risk factors and prognosis of lung involvements in rheumatic diseases. Moreover, the pathogenesis particularly in the context of genetics has been greatly updated for both the underlying rheumatic disease and associated lung involvement. This review will focus on the current update on the epidemiologic and genetics features and treatment options of the lung involvements associated with four major rheumatic diseases (rheumatoid arthritis, systemic sclerosis, myositis, and systemic lupus erythematosus), with more attention to a specific form of involvement or interstitial lung disease.
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Relationship between interstitial lung disease and oesophageal dilatation on chest high-resolution computed tomography in patients with systemic sclerosis: a cross-sectional study. Radiol Med 2018; 123:655-663. [PMID: 29687210 DOI: 10.1007/s11547-018-0894-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 04/11/2018] [Indexed: 01/04/2023]
Abstract
OBJECTIVES Oesophageal dilatation (OD) has been implicated in the pathogenesis of interstitial lung disease (ILD) in systemic sclerosis (SSc). The aims of this study were to explore the association of the OD and SSc-ILD on chest high-resolution computed tomography (HRCT), and to establish a cutoff point for the OD suggestive for the presence of a significant lung involvement. METHODS The widest oesophageal diameter (WOD) was obtained on axial HRCT images. The parenchymal abnormalities on HRCT were coded and scored according to Warrick method. Patient-centred measures, pulmonary function tests and the single breath carbon monoxide diffusing capacity of the lung (DLco) were also obtained. Multivariate regression analysis was performed to identify factors associated with oesophageal diameter. RESULTS 126 subjects with SSc were included. The mean (± SD) WOD was 13.5 (± 4.2) mm, and in 76 (60.3%) participants WOD was ≥ 11 mm. SSc patients with ILD had larger oesophageal diameters than those without lung disease (19.4 vs. 14.1 mm, p < 0.001). We observed a high correlation between WOD and gastro-oesophageal reflux disease questionnaire (GerdQ) (r = 0.886, p < 0.001), Borg score (r = 0.705, p < 0.001), and Warrick score (r = 0.614, p < 0.001). WOD negatively correlated with DLco (r = - 0.508, p < 0.001). Multivariate analysis demonstrated positive associations between WOD and GerdQ (p < 0.0001), Borg score (p < 0.0005), and total Warrick score (p = 0.019). CONCLUSION An increased oesophageal diameter (> 11 mm) on chest HRCT is associated with pulmonary and oesophageal symptoms, more severe ILD, and lower DLco.
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Winstone TA, Hague CJ, Soon J, Sulaiman N, Murphy D, Leipsic J, Dunne JV, Wilcox PG, Ryerson CJ. Oesophageal diameter is associated with severity but not progression of systemic sclerosis-associated interstitial lung disease. Respirology 2018; 23:921-926. [DOI: 10.1111/resp.13309] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 01/15/2018] [Accepted: 03/13/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Tiffany A. Winstone
- Department of Medicine; University of British Columbia; Vancouver BC Canada
- Centre for Heart Lung Innovation; University of British Columbia; Vancouver BC Canada
| | - Cameron J. Hague
- Department of Radiology; University of British Columbia; Vancouver BC Canada
| | - Jeanette Soon
- Department of Radiology; University of British Columbia; Vancouver BC Canada
| | - Nada Sulaiman
- Department of Radiology; University of British Columbia; Vancouver BC Canada
| | - Darra Murphy
- Department of Radiology; University of British Columbia; Vancouver BC Canada
| | - Jonathon Leipsic
- Department of Radiology; University of British Columbia; Vancouver BC Canada
| | - James V. Dunne
- Department of Medicine; University of British Columbia; Vancouver BC Canada
| | - Pearce G. Wilcox
- Department of Medicine; University of British Columbia; Vancouver BC Canada
| | - Christopher J. Ryerson
- Department of Medicine; University of British Columbia; Vancouver BC Canada
- Centre for Heart Lung Innovation; University of British Columbia; Vancouver BC Canada
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McFarlane IM, Bhamra MS, Kreps A, Iqbal S, Al-Ani F, Saladini-Aponte C, Grant C, Singh S, Awwal K, Koci K, Saperstein Y, Arroyo-Mercado FM, Laskar DB, Atluri P. Gastrointestinal Manifestations of Systemic Sclerosis. ACTA ACUST UNITED AC 2018; 8. [PMID: 30057856 PMCID: PMC6059963 DOI: 10.4172/2161-1149.1000235] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibroproliferative alterations of the microvasculature leading to fibrosis and loss of function of the skin and internal organs. Gastrointestinal manifestations of SSc are the most commonly encountered complications of the disease affecting nearly 90% of the SSc population. Among these complications, the esophagus and the anorectum are the most commonly affected. However, this devastating disorder does not spare any part of the gastrointestinal tract (GIT), and includes the oral cavity, esophagus, stomach, small and large bowels as well as the liver and pancreas. In this review, we present the current understanding of the pathophysiologic mechanisms of SSc including vasculopathy, endothelial to mesenchymal transformation as well as the autoimmune pathogenetic pathways. We also discuss the clinical presentation and diagnosis of each part of the GIT affected by SSc. Finally, we highlight the latest developments in the management of this disease, addressing the severe malnutrition that affects this vulnerable patient population and ways to assess and improve the nutritional status of the patients.
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Affiliation(s)
- Isabel M McFarlane
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Manjeet S Bhamra
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Alexandra Kreps
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Sadat Iqbal
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Firas Al-Ani
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Carla Saladini-Aponte
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Christon Grant
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Soberjot Singh
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Khalid Awwal
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Kristaq Koci
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Yair Saperstein
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Fray M Arroyo-Mercado
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Derek B Laskar
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
| | - Purna Atluri
- Division of Rheumatology and Gastroenterology, Department of Medicine and Pathology, Hospitals Kings County Hospital Brooklyn, State University of New York, USA
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Stern EK, Carlson DA, Falmagne S, Hoffmann AD, Carns M, Pandolfino JE, Hinchcliff M, Brenner DM. Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients. Neurogastroenterol Motil 2018; 30:10.1111/nmo.13247. [PMID: 29110377 PMCID: PMC5771836 DOI: 10.1111/nmo.13247] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 10/09/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Esophageal dysfunction and gastro-esophageal reflux disease (GERD) are common among patients with systemic sclerosis (SSc). Although high-dose proton pump inhibitors (PPIs) typically normalize esophageal acid exposure, the effectiveness of PPI therapy has not been systematically studied in SSc patients. The aim of this study was to characterize reflux in SSc patients on high-dose PPI using esophageal pH-impedance testing. METHODS In this case-controlled retrospective analysis, 38 patients fulfilling 2013 American College of Rheumatology SSc criteria who underwent esophageal pH-impedance testing on twice-daily PPI between January 2014 and March 2017 at a tertiary referral center were compared with a control-cohort of 38 non-SSc patients matched for PPI formulation and dose, hiatal hernia size, age, and gender. Patient clinical characteristics, including endoscopy and high-resolution manometry findings, were assessed via chart review. KEY RESULTS On pH-impedance, SSc patients had higher acid exposure times (AETs) than controls. Sixty-one percent of the SSc patients and 18% of the control patients had a total AET ≥4.5% (P < .001). Systemic sclerosis patients also had significantly longer AETs, longer median bolus clearance, and lower nocturnal impedance values. CONCLUSIONS & INFERENCES Abnormal esophageal acid exposure despite high-dose PPI therapy was common among patients with SSc. The lack of increased reflux episodes in the SSc patients, and longer bolus clearance times and lower nocturnal impedance, supports ineffective clearance as the potential mechanism. Systemic sclerosis patients may require adjunctive therapies to PPIs to control acid reflux.
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Affiliation(s)
- Emily K. Stern
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Dustin A. Carlson
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Sophia Falmagne
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Aileen D. Hoffmann
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Mary Carns
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - John E. Pandolfino
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Monique Hinchcliff
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Darren M. Brenner
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Lung Manifestations in the Rheumatic Diseases. Chest 2017; 152:1283-1295. [PMID: 28552544 DOI: 10.1016/j.chest.2017.05.015] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 05/15/2017] [Accepted: 05/16/2017] [Indexed: 12/21/2022] Open
Abstract
Lung ailments in rheumatic diseases present unique challenges for diagnosis and management and are a source of significant morbidity and mortality for patients. Unlike the idiopathic interstitial pneumonias, patients with rheumatic diseases experience lung disease in the context of a systemic disease that may make it more difficult to recognize and that may present greater risks with treatment. Despite recent advances in our awareness of these diseases, there is still a significant lack of understanding of natural history to elucidate which patients will have disease that is progressive and thus warrants treatment. What we do know is that a subset of patients with rheumatic disease experience parenchymal lung disease that can prognostically resemble idiopathic pulmonary fibrosis, such as in rheumatoid arthritis, and that others can have aggressive inflammatory lung disease in the context of autoimmune myositis, systemic sclerosis, or an undifferentiated autoimmune process. As we enter into a paradigm shift where we view lung health as a cornerstone of our care of patients with rheumatic diseases, we hopefully will improve our ability to identify those patients at highest risk for pulmonary disease and progression, and offer emerging treatments which will result in better outcomes and a better quality of life.
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Kumar S, Singh J, Rattan S, DiMarino AJ, Cohen S, Jimenez SA. Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis. Aliment Pharmacol Ther 2017; 45:883-898. [PMID: 28185291 PMCID: PMC5576448 DOI: 10.1111/apt.13963] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 11/18/2016] [Accepted: 01/11/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. AIMS To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets. METHODS Electronic (PubMed/Medline) and manual Google search. RESULTS The GIT is the most common internal organ involved in SSc. Any part of the GIT from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are nonspecific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the absence of cutaneous disease. Up to 8% of SSc patients develop severe GIT symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the GIT causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of GIT dysmotility mediated by functional anti-muscarinic receptor autoantibodies. CONCLUSIONS Despite extensive investigation, the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions.
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Affiliation(s)
- Sumit Kumar
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA
| | - Jagmohan Singh
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA
| | - Satish Rattan
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA
| | - Anthony J DiMarino
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA
| | - Sidney Cohen
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA
| | - Sergio A. Jimenez
- Jefferson Institute of Molecular Medicine and Scleroderma Center, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA
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