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Nakamura T, Jinta T, Kitamura A, Tanaka M, So C, Ro S, Imai R, Okafuji K, Tomishima Y, Nishimura N. Differences in Tolerability of Antifibrotic Agents Between Connective Tissue Disease-Associated and Non-connective Tissue Disease-Associated Interstitial Lung Disease. Cureus 2025; 17:e78750. [PMID: 40070627 PMCID: PMC11896007 DOI: 10.7759/cureus.78750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/08/2025] [Indexed: 03/14/2025] Open
Abstract
Background Although antifibrotic agents (AFAs) are often discontinued due to side effects, their tolerability is crucial given the limited treatment options for interstitial lung disease associated with connective tissue disease (CTD-ILD). The possibility of intolerance due to organ damage caused by CTDs has also been considered; however, few detailed studies are available. We hypothesized that AFAs for CTD-ILD would be poorly tolerated or discontinued prematurely due to organ damage caused by collagen disease. Therefore, we conducted a retrospective investigation to explore this hypothesis. Methods We retrospectively reviewed the medical records of ILD patients treated with nintedanib or pirfenidone at St. Luke's International Hospital between December 2008 and November 2022, comparing the CTD-ILD group with the non-CTD-ILD group. Patient background, cumulative discontinuation rate due to adverse events (AEs), duration of prescription until discontinuation, AEs leading to discontinuation, and mortality rate were collected from medical records. Results We identified 42 and 129 patients in the CTD-ILD and non-CTD-ILD groups, respectively. The cumulative incidence of discontinuation due to AEs did not significantly differ between the CTD-ILD and non-CTD-ILD groups in the overall population or when restricted to nintedanib and pirfenidone (overall population, p = 0.402; nintedanib group, p = 0.510; pirfenidone group, p = 0.625). The duration of AFA use at discontinuation due to AEs was not significantly different between the overall group (CTD-ILD vs. non-CTD-ILD, median: 77 vs. 116 days, p = 0.496) and the pirfenidone group (CTD-ILD vs. non-CTD-ILD, median: 136 vs. 55 days, p = 0.127). However, for nintedanib, the duration in the CTD-ILD group was significantly shorter than that in the non-CTD-ILD group (median: 23 vs. 218 days, p = 0.016). Gastrointestinal symptoms were the most common reason for discontinuation. Of the seven cases of CTD-ILD patients who used nintedanib and discontinued due to AEs, six were female, four had systemic sclerosis (SSc), and three were using tacrolimus. Conclusions The cumulative incidence of discontinuations due to AEs did not significantly differ between the CTD-ILD and non-CTD-ILD groups. However, the duration of nintedanib use was significantly shorter in the CTD-ILD group when the discontinuation was due to AEs. Particularly, when administering nintedanib to patients with SSc and/or those using tacrolimus, measures to prevent AEs should be carefully implemented.
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Affiliation(s)
- Tomoaki Nakamura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Torahiko Jinta
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Atsushi Kitamura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Michiho Tanaka
- Department of Pulmonary Medicine, Thoracic Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, JPN
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Clara So
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Shosei Ro
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Ryosuke Imai
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Kohei Okafuji
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Yutaka Tomishima
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
| | - Naoki Nishimura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, JPN
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Rodolfi S, Denton CP, Ong VH. Systemic sclerosis-associated severe gastric antral vascular ectasia treated with tocilizumab:A case report and review of the literature. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2025:23971983241309570. [PMID: 39802335 PMCID: PMC11713938 DOI: 10.1177/23971983241309570] [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: 11/01/2024] [Accepted: 12/06/2024] [Indexed: 01/16/2025]
Abstract
Gastric antral vascular ectasia is a frequent and potentially severe complication of systemic sclerosis. Management is presently limited to supportive care, acid suppression and endoscopic treatment. Many cases of gastric antral vascular ectasia tend to be refractory or partially responsive to standard treatment and require multiple endoscopic procedures to control the recurrent bleeding. Immunosuppression is not part of the recommended management of gastric antral vascular ectasia: limited data exist on the role of cyclophosphamide or autologous stem cell transplant in severe cases, but no prospective data or randomised controlled trial supports its routine use. Here, we present a case of an adult male patient with diffuse cutaneous systemic sclerosis complicated by arthritis and severe gastric antral vascular ectasia. The latter required multiple endoscopic procedures and remained transfusion-dependent. Due to progressive skin disease and active arthritis refractory to conventional synthetic disease-modifying antirheumatic drugs, the patient was started on tocilizumab. While he showed an early response in terms of scores related to skin involvement and arthritis, response to gastric antral vascular ectasia was unexpected. As soon as the biologic therapy was started, the patient was no longer transfusion-dependent and haemoglobin levels started to rise. Subsequent endoscopic investigations confirmed resolution of gastric antral vascular ectasia. This case is illustrative of an unexpected response to tocilizumab, and this observation is supported by the biological rationale of interleukin-6 in vascular remodelling.
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Affiliation(s)
| | | | - Voon H Ong
- University College London Medical School, London, UK
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3
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Wąż K, Kucharz EJ, Kopeć-Mędrek M, Machura-Porębska E, Pieczyrak R, Kotyla P. Low serum zonulin level in patients with systemic sclerosis. Reumatologia 2024; 62:389-390. [PMID: 39677879 PMCID: PMC11635621 DOI: 10.5114/reum/194846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 10/02/2024] [Indexed: 12/17/2024] Open
Affiliation(s)
- Karolina Wąż
- Department of Internal Medicine, Rheumatology and Clinical Immunology, Medical University of Silesia, Katowice, Poland
| | - Eugeniusz J Kucharz
- Department of Internal Medicine, Rheumatology and Clinical Immunology, Medical University of Silesia, Katowice, Poland
| | - Magdalena Kopeć-Mędrek
- Department of Internal Medicine, Rheumatology and Clinical Immunology, Medical University of Silesia, Katowice, Poland
| | - Ewelina Machura-Porębska
- Department of Internal Medicine, Rheumatology and Clinical Immunology, Medical University of Silesia, Katowice, Poland
| | - Robert Pieczyrak
- Department of Internal Medicine, Rheumatology and Clinical Immunology, Medical University of Silesia, Katowice, Poland
| | - Przemysław Kotyla
- Department of Internal Medicine, Rheumatology and Clinical Immunology, Medical University of Silesia, Katowice, Poland
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Garrote-Corral S, Botello Corzo D, Loarce-Martos J, de la Puente Bujidos C, Carmona L. Efficacy and safety of intravenous immunoglobulin therapy in systemic sclerosis: a systematic review. Rheumatol Int 2024; 44:2357-2370. [PMID: 38748220 DOI: 10.1007/s00296-024-05613-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 04/30/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND AND OBJECTIVE Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc. METHODS The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies. RESULTS From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash. CONCLUSION Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations.
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Affiliation(s)
- Sandra Garrote-Corral
- Department of Rheumatology, Hospital Universitario Ramon y Cajal, M-607, 9, 100, 28034, Madrid, Spain.
| | - Diana Botello Corzo
- Department of Rheumatology, Hospital Universitario Materno Insular, Gran Canaria, Las Palmas Gran Canaria, Spain
| | - Jesús Loarce-Martos
- Department of Rheumatology, Hospital Universitario Ramon y Cajal, M-607, 9, 100, 28034, Madrid, Spain
| | | | - Loreto Carmona
- Instituto de Salud Musculoesquelética (InMusc), Madrid, Spain
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Cheah JX, Perin J, Hughes M, Mecoli CA, Paik JJ, Hummers LK, Shah AA, McMahan ZH. Demographics and Clinical Features Associated with Abnormal Small Bowel Motility in Systemic Sclerosis. Rheumatology (Oxford) 2024:keae542. [PMID: 39374539 DOI: 10.1093/rheumatology/keae542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 09/03/2024] [Accepted: 09/14/2024] [Indexed: 10/09/2024] Open
Abstract
OBJECTIVE The small bowel is affected in up to 50% of systemic sclerosis (SSc) patients, and some patients experience severe complications. Our aim was to use specific statistical methods to compare demographic and clinical features of SSc patients with and without abnormal small bowel to better characterize patients at risk for this complication. METHODS SSc patients with gastrointestinal symptoms were prospectively enrolled and underwent a scintigraphy-based whole gut transit (WGT) study. A cross-sectional analysis was performed comparing clinical features between patients with and without abnormal small bowel transit by WGT. Univariate logistic regression models and multivariable models were used to examine the relationship between clinical features and abnormal small bowel transit. RESULTS Of 130 patients enrolled in this study, 22 had abnormal small bowel transit. SSc patients with abnormal small bowel transit were more likely to be male [Odds Ratio(OR)=3.70, Confidence Interval(CI) 1.07-12.50, p= 0.038], and have more severe cardiac involvement (OR = 3.98, CI 1.10-14.38, p= 0.035), while they were less likely to have sicca symptoms (OR = 0.30, CI 0.10-0.94, p= 0.039). In multivariable analyses, sicca symptoms (OR = 0.28, CI 0.08-0.96, p= 0.043) remained negatively associated with abnormal small bowel transit. Additionally, SSc patients with abnormal small bowel transit had higher mortality than patients with normal small bowel transit [Hazard ratio(HR)=4.57, CI 1.58-13.24, p= 0.005]. CONCLUSIONS These findings suggest that patients with abnormal small bowel transit in SSc are more likely to be male, have more severe cardiac involvement, higher mortality, and less sicca symptoms. Recognizing this patient subgroup is essential for risk stratification and optimizing clinical care.
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Affiliation(s)
- Jenice X Cheah
- Department of Medicine, University of California-Los Angeles, Los Angeles, CA
| | - Jamie Perin
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Michael Hughes
- Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Christopher A Mecoli
- Johns Hopkins University, Department of Medicine, Division of Rheumatology, Baltimore, MD
| | - Julie J Paik
- Johns Hopkins University, Department of Medicine, Division of Rheumatology, Baltimore, MD
| | - Laura K Hummers
- Johns Hopkins University, Department of Medicine, Division of Rheumatology, Baltimore, MD
| | - Ami A Shah
- Johns Hopkins University, Department of Medicine, Division of Rheumatology, Baltimore, MD
| | - Zsuzsanna H McMahan
- Division of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX
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Pellicano C, Oliva A, Colalillo A, Gigante A, D'Aliesio E, Al Ismail D, Miele MC, Cianci R, Mastroianni CM, Rosato E. Serum markers of microbial translocation and intestinal damage in assessment of gastrointestinal tract involvement in systemic sclerosis. Clin Exp Med 2024; 24:225. [PMID: 39294494 PMCID: PMC11410972 DOI: 10.1007/s10238-024-01466-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 08/14/2024] [Indexed: 09/20/2024]
Abstract
Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score "moderate-to-very severe" [OR 1.001 (CI 95%: 1.001-1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023-1.506), p < 0.05] as variables associated with UCLA distension/bloating "moderate-to-very severe". The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea "moderate-to-very severe" [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms.
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Affiliation(s)
- Chiara Pellicano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185, Rome, Italy
| | - Amalia Colalillo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy
| | - Antonietta Gigante
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy
| | - Elisa D'Aliesio
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185, Rome, Italy
| | - Dania Al Ismail
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185, Rome, Italy
| | - Maria Claudia Miele
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185, Rome, Italy
| | - Rosario Cianci
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy
| | - Claudio Maria Mastroianni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185, Rome, Italy
| | - Edoardo Rosato
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy.
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7
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Wang X, Li H, Ding Y, Yu J, Huang WF. An unusual cause of gastrointestinal bleeding: "Watermelon stomach". Am J Med Sci 2024; 368:e23-e26. [PMID: 38460921 DOI: 10.1016/j.amjms.2024.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/25/2023] [Accepted: 03/05/2024] [Indexed: 03/11/2024]
Affiliation(s)
- Xu Wang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Hua Li
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Yi Ding
- Department of Pathology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Juan Yu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Wei-Feng Huang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
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8
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Gowda SK, Garg S, Khajjayam A, Sahu SK, Kaur M, Patra S, Behera B, Thakur V. Superior mesenteric artery syndrome - An unusual presentation associated with diffuse cutaneous systemic sclerosis in two cases. Indian J Dermatol Venereol Leprol 2024; 0:1-3. [PMID: 39152842 DOI: 10.25259/ijdvl_315_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 03/25/2024] [Indexed: 08/19/2024]
Affiliation(s)
- Shreya K Gowda
- Department of Dermatology and Venereology, AIIMS, Bhopal, Madhya Pradesh, India
| | - Sonika Garg
- Department of Dermatology, All India Institute of Medical Sciences, Bhubaneswar, India
| | | | - Shantanu Kumar Sahu
- Department of General Surgery, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Maninder Kaur
- Department of Dermatology and Venereology, AIIMS, Bhopal, Madhya Pradesh, India
| | - Suman Patra
- Department of Dermatology and Venereology, AIIMS, Bhopal, Madhya Pradesh, India
| | - Biswanath Behera
- Department of Dermatology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Vishal Thakur
- Department of Dermatology, All India Institute of Medical Sciences, Bhubaneswar, India
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9
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Dima A, Vonk MC, Garaiman A, Kersten BE, Becvar R, Tomcik M, Hoffmann-Vold AM, Castellvi I, Jaime JT, Brzosko M, Milchert M, Krasowska D, Michalska-Jakubus M, Airo P, Matucci-Cerinic M, Bruni C, Iudici M, Distler J, Gheorghiu AM, Poormoghim H, Motta F, De Santis M, Parvu M, Distler O, Mihai C. Clinical significance of the anti-Nucleolar Organizer Region 90 antibodies (NOR90) in systemic sclerosis: Analysis of the European Scleroderma Trials and Research (EUSTAR) cohort and a systematic literature review. Eur J Intern Med 2024; 125:104-110. [PMID: 38599922 DOI: 10.1016/j.ejim.2024.03.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 03/11/2024] [Accepted: 03/29/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain. OBJECTIVES To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort. METHODS Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023. RESULTS Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %. CONCLUSION To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.
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Affiliation(s)
- A Dima
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland; Department of Rheumatology, Colentina Clinical Hospital, 19-21 Stefan cel Mare, 020125 Bucharest, Romania.
| | - M C Vonk
- Department of the Rheumatology, Radboud University Nijmegen Medical Centre Huispost 667, 6500HB Nijmegen, the Netherlands
| | - A Garaiman
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland
| | - B E Kersten
- Department of the Rheumatology, Radboud University Nijmegen Medical Centre Huispost 667, 6500HB Nijmegen, the Netherlands
| | - R Becvar
- Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University - Na Slupi 4, 12800 Praha 2, Czechia
| | - M Tomcik
- Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University - Na Slupi 4, 12800 Praha 2, Czechia
| | - A-M Hoffmann-Vold
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland; Department of Rheumatology, Rikshospitalet University Hospital - Sognsvannveien 20, 0027 Oslo, Norway
| | - I Castellvi
- Department of Rheumatology, Hospital Universitari de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167 Barcelona, Spain
| | - Jl Tandaipan Jaime
- Department of Rheumatology, Hospital Universitari de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167 Barcelona, Spain
| | - M Brzosko
- Department of Internal Medicine Rheumatology Diabetology Geriatrics and Clinical Immunology, Pomeranian Medical University in Szczecin, Ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland
| | - M Milchert
- Department of Internal Medicine Rheumatology Diabetology Geriatrics and Clinical Immunology, Pomeranian Medical University in Szczecin, Ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland
| | - D Krasowska
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Staszica 11L, 20-081 Lublin, Poland
| | - M Michalska-Jakubus
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Staszica 11L, 20-081 Lublin, Poland
| | - P Airo
- 9 Spedali Civili di Brescia, Scleroderma UNIT, UOC Reumatologia ed Immunologia Clinica, Piazzale Spedali Civili 1, 25123 Brescia, Italy
| | - M Matucci-Cerinic
- Department of Experimental and Clinical Medicine, University of Florence & Division of Rheumatology AOUC, Florence, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - C Bruni
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland; Department of Experimental and Clinical Medicine, University of Florence & Division of Rheumatology AOUC, Florence, Italy
| | - M Iudici
- Rheumatology Unit, Geneva University Hospitals, 1211 Geneva 14, Switzerland
| | - Jhw Distler
- Department of Rheumatology, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
| | - A M Gheorghiu
- Department of Internal Medicine and Rheumatology Clinic, Ion Cantacuzino Hospital - Ion Movila Street 5-7, 020475 Bucharest, Romania
| | - H Poormoghim
- Department of Rheumatology, Firoozgar Hospital - Beh Afarin street, Tehran, Iran
| | - F Motta
- Department of Biomedical Sciences, Humanitas University, via R Levi Montalcini, 20090, Pieve Emanuele, Italy; Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via A Manzoni 56, 20089, Rozzano, Milan, Italy
| | - M De Santis
- Department of Biomedical Sciences, Humanitas University, via R Levi Montalcini, 20090, Pieve Emanuele, Italy; Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via A Manzoni 56, 20089, Rozzano, Milan, Italy
| | - M Parvu
- Department of Rheumatology, Colentina Clinical Hospital, 19-21 Stefan cel Mare, 020125 Bucharest, Romania
| | - O Distler
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland
| | - C Mihai
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland
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10
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Marchetti L, Rogers BD, Hengehold T, Sifrim D, Gyawali CP. Saliva Production and Esophageal Motility Influence Esophageal Acid Clearance Related to Post-reflux Swallow-Induced Peristaltic Wave. Dig Dis Sci 2024; 69:1714-1721. [PMID: 38528208 DOI: 10.1007/s10620-024-08315-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 01/23/2024] [Indexed: 03/27/2024]
Abstract
BACKGROUND The post-reflux swallow-induced peristaltic wave (PSPW) brings salivary bicarbonate to neutralize residual distal esophageal mucosal acidification. AIMS To determine if reduced saliva production and esophageal body hypomotility would compromise PSPW-induced pH recovery in the distal esophagus. METHODS In this multicenter retrospective cross-sectional study, patients with confirmed Sjogren's syndrome and scleroderma/mixed connective tissue disease (MCTD) who underwent high resolution manometry (HRM) and ambulatory pH-impedance monitoring off antisecretory therapy were retrospectively identified. Patients without these disorders undergoing HRM and pH-impedance monitoring for GERD symptoms were identified from the same time-period. Acid exposure time, numbers of reflux episodes and PSPW, pH recovery with PSPW, and HRM metrics were extracted. Univariate comparisons and multivariable analysis were performed to determine predictors of pH recovery with PSPW. RESULTS Among Sjogren's syndrome (n = 34), scleroderma/MCTD (n = 14), and comparison patients with reflux symptoms (n = 96), the scleroderma/MCTD group had significantly higher AET, higher prevalence of hypomotility, lower detected reflux episodes, and very low numbers of PSPW (p ≤ 0.004 compared to other groups). There was no difference in pH-impedance metrics between Sjogren's syndrome, and comparison patients (p ≥ 0.481). Proportions with complete pH recovery with PSPW was lower in Sjogren's patients compared to comparison reflux patients (p = 0.009), predominantly in subsets with hypomotility (p < 0.001). On multivariable analysis, diagnosis of Sjogren's syndrome, scleroderma/MCTD or neither (p = 0.014) and esophageal hypomotility (p = 0.024) independently predicted lack of complete pH recovery with PSPW, while higher total reflux episodes trended (p = 0.051). CONCLUSIONS Saliva production and motor function are both important in PSPW related pH recovery.
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Affiliation(s)
- Lorenzo Marchetti
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Benjamin D Rogers
- Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Ave.,, Campus Box 8124, Saint Louis, MO, 63110, USA
- Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA
| | - Tricia Hengehold
- Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Ave.,, Campus Box 8124, Saint Louis, MO, 63110, USA
- Division of Gastroenterology, Ohio State University, Columbus, OH, USA
| | - Daniel Sifrim
- Wingate Institute, Queen Mary University of London, London, UK
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Ave.,, Campus Box 8124, Saint Louis, MO, 63110, USA.
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11
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Foeldvari I, Torok KS, Antón J, Blakley M, Constantin T, Cutolo M, Denton CP, Fligelstone K, Hinrichs B, Li SC, Maillard S, Marrani E, Moinzadeh P, Orteu CH, Pain CE, Pauling JD, Pilkington C, Rosser F, Smith V, Furst DF. Best clinical practice in the treatment of juvenile systemic sclerosis: expert panel guidance - the result of the International Hamburg Consensus Meeting December 2022. Expert Rev Clin Immunol 2024; 20:387-404. [PMID: 38149621 DOI: 10.1080/1744666x.2023.2298354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/19/2023] [Indexed: 12/28/2023]
Abstract
INTRODUCTION Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed. AREAS COVERED Treatment options were reviewed, and opinions were provided for most facets of jSSc including general management, some of which differs from adult systemic sclerosis, such as the use of corticosteroids, and specific organ involvement, such as skin, musculoskeletal, pulmonary, and gastroenterology. EXPERT OPINION We are suggesting the treat to target strategy to treat early to prevent cumulative disease damage in jSSc. Conclusions are derived from both expert opinion and available literature, which is mostly based on adult systemic sclerosis (aSSc), given shared pathophysiology, extrapolation of results from aSSc studies was judged reasonable.
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Affiliation(s)
- Ivan Foeldvari
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
| | - Kathryn S Torok
- University of Pittsburgh and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Jordi Antón
- Department of Pediatric Rheumatology. Hospital Sant Joan de Déu and Universitat de Barcelona, Barcelona, Spain
| | - Michael Blakley
- Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tamás Constantin
- Unit of Pediatric Rheumatology, Tűzoltó Street Department, Pediatric Centre, Semmelweis University, Budapest, Hungary
| | - Maurizio Cutolo
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology-Department of Internal Medicine and Specialties, University of Genoa and IRCCS San Martino Polyclinic Hospital, Genoa, Italy
| | | | - Kim Fligelstone
- Scleroderma & Raynaud's United Kindgom (SRUK) (Research Subcommittee, Patient Research Partner), FESCA, London, UK
| | - Bernd Hinrichs
- Children's pulmonology, Asklepios Klinik Nord - Heidberg, Hamburg, Germany
| | - Suzanne C Li
- Hackensack University Medical Center, Hackensack, NJ, USA
| | | | - Edoardo Marrani
- Pediatric Rheumatology Unit, Meyer Children's Hospital IRCCS, Florence, Italy
| | - Pia Moinzadeh
- Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany
| | - Catherine H Orteu
- UCL Institute of Immunity and Transplantation, Royal Free London NHS Foundation Trust, London, UK
| | - Clare E Pain
- Alder Hey Children's Foundation NHS Trust, Liverpool, UK
| | - John D Pauling
- Department of Internal Medicine, Ghent University, Ghent, Belgium
- Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
- Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium and ERN ReCONNET
| | | | - Franziska Rosser
- University of Pittsburgh and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Vanessa Smith
- University of California, Los Angeles, CA, USA
- University of Washington, Seattle, WA, USA
- University of Florence, Florence, Italy
| | - Daniel F Furst
- Division of Rheumatology Fellow, Geffen School of Medicine at the University of California in Los Angeles, Los Angeles, CA, USA
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12
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Suzon B, Louis-Sidney F, Abel A, Moinet F, Bagoée C, Henry K, Coco-Viloin I, Cougnaud R, Wolff S, Guilpain P, Rivière S, Flori N, Deligny C, Maria A. [Severe small bowel involvement and chronic intestinal pseudo-obstruction in systemic sclerosis (scleroderma): Pathophysiological, diagnostic and therapeutic basis, including parenteral nutrition]. Rev Med Interne 2024; 45:147-155. [PMID: 38388303 DOI: 10.1016/j.revmed.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 01/15/2024] [Accepted: 02/03/2024] [Indexed: 02/24/2024]
Abstract
Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.
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Affiliation(s)
- B Suzon
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique; Unité EpiCliV, Université des Antilles, Fort-de-France, Martinique.
| | - F Louis-Sidney
- Unité EpiCliV, Université des Antilles, Fort-de-France, Martinique; Rhumatologie, CHU de Martinique, Fort-de-France, Martinique
| | - A Abel
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - F Moinet
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - C Bagoée
- Médecine interne et polyvalente, Centre hospitalier territorial Gaston-Bourret, Nouméa, Nouvelle-Calédonie
| | - K Henry
- Maladies infectieuses et tropicales, Centre hospitalier de Cayenne, Cayenne, Guyane
| | - I Coco-Viloin
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - R Cougnaud
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - S Wolff
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - P Guilpain
- Médecine interne et maladies multi-organiques, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France; Institut de médecine régénérative et biothérapies, Inserm U1183, Montpellier, France; Faculté de médecine, Université de Montpellier, Montpellier, France
| | - S Rivière
- Médecine interne et maladies multi-organiques, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France
| | - N Flori
- Centre expert régional de nutrition, ICM, Montpellier, France
| | - C Deligny
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique; Unité EpiCliV, Université des Antilles, Fort-de-France, Martinique
| | - A Maria
- Institut de médecine régénérative et biothérapies, Inserm U1183, Montpellier, France; Faculté de médecine, Université de Montpellier, Montpellier, France; Médecine interne et immuno-oncologie (MedI2O), Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
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13
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Ramegowda R, Singhal M, Gulati A, Samanta J, Singh H, Sharma V, Sharma A, Gupta P. Autoimmune disorders of the gastrointestinal tract: Review of radiological appearances. Curr Probl Diagn Radiol 2024; 53:259-270. [PMID: 37923635 DOI: 10.1067/j.cpradiol.2023.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 09/26/2023] [Accepted: 10/18/2023] [Indexed: 11/07/2023]
Abstract
Autoimmune gastrointestinal (GI) disorders comprise a heterogeneous group of diseases with non-specific clinical manifestations. These are divided into primary and secondary. A high index of clinical suspicion complemented with endoscopic and radiological imaging may allow early diagnosis. Due to the relatively low incidence of autoimmune disorder, the imaging literature is sparse. In this review, we outline the pathogenesis, classification, and imaging appearances of autoimmune GI disorders.
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Affiliation(s)
- Rajath Ramegowda
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manphool Singhal
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Gulati
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jayanta Samanta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Harjeet Singh
- Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aman Sharma
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pankaj Gupta
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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14
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García JR, Arranz MM. Afectación gástrica en las enfermedades sistémicas y hepáticas. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2024; 14:148-152. [DOI: 10.1016/j.med.2024.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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15
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Songtanin B, Jacob R, Nugent K. Recurrent spontaneous pneumoperitoneum in a patient with systemic sclerosis. BMJ Case Rep 2023; 16:e258041. [PMID: 37996130 PMCID: PMC10668157 DOI: 10.1136/bcr-2023-258041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023] Open
Affiliation(s)
- Busara Songtanin
- Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Roy Jacob
- Radiology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Kenneth Nugent
- Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
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16
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Szeto L, Yazdian A, Parkman HP. Atypical Causes of Gastroparesis: Prevalence, Gastric Emptying, and Clinical Features. J Clin Gastroenterol 2023; 57:895-900. [PMID: 36730846 DOI: 10.1097/mcg.0000000000001786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 09/27/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gastroparesis is commonly attributed to idiopathic or diabetic causes. GOALS We aimed to describe atypical causes of gastroparesis and examine the clinical features and severity of delayed gastric emptying compared with idiopathic and diabetic causes. STUDY Between 2018 and 2021, gastroparesis patients being evaluated at our tertiary care center completed a 4-hour gastric emptying scintigraphy and questionnaires assessing for gastrointestinal disorders, including patient assessment of upper gastrointestinal symptoms. Patients were divided into groups relating to gastroparesis cause: diabetic, postsurgical (PSGp), connective tissue (CTGp), neurological and idiopathic. RESULTS Two hundred fifty-six patients with delayed emptying on gastric emptying scintigraphy completed the questionnaires. Gastroparesis causes included 149 (58.2%) idiopathic, 60 (23.4%) diabetic, 29 (11.3%) postsurgical, 13 (5.1%) connective tissue, and 5 (2.0%) neurological. In each group, most patients were female and White. Gastric retention at 4 hours was significantly greater in patients with diabetic (39.3±25.7% P <0.001), postsurgical (41.3±24.0% P =0.002), and connective tissue gastroparesis (37.8±20.0% P =0.049) compared with patients with idiopathic gastroparesis (25.5±17.6%). In PSGp, diabetic and idiopathic causes, the main symptoms were early satiety and postprandial fullness, whereas in CTGp, bloating and abdominal distension were the predominant symptoms. Vomiting severity was significantly greater in patients with diabetes compared with idiopathic gastroparesis (2.9±1.9 vs. 2.1±1.8 P =0.006). CONCLUSIONS Atypical causes contributed to gastroparesis in 47 of 256 (18.4%) patients with delayed gastric emptying. Gastric emptying was significantly more delayed in PSGp and CTGp patients. PSGp patients mainly experienced stomach fullness and early satiety, whereas CTGp patients had predominantly bloating and distension.
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Affiliation(s)
- Lauren Szeto
- Department of Internal Medicine, Temple University Hospital
| | - Aaron Yazdian
- Department of Internal Medicine, Temple University Hospital
| | - Henry P Parkman
- Section of Gastroenterology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA
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17
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Herrán M, Adler BL, Perin J, Morales W, Pimentel M, McMahan ZH. Antivinculin Antibodies in Systemic Sclerosis: Associations With Slow Gastric Transit and Extraintestinal Clinical Phenotype. Arthritis Care Res (Hoboken) 2023; 75:2166-2173. [PMID: 36951252 PMCID: PMC10517080 DOI: 10.1002/acr.25118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 12/19/2022] [Accepted: 03/21/2023] [Indexed: 03/24/2023]
Abstract
OBJECTIVE The gastrointestinal (GI) tract is commonly affected in systemic sclerosis (SSc). A positive association between antivinculin antibody levels and GI symptom severity is reported in SSc. We sought to examine whether antivinculin antibodies associate with measures of GI dysmotility and extraintestinal clinical phenotype in SSc. METHODS A total of 88 well-characterized patients with SSc and GI disease were assayed for antivinculin antibodies by enzyme-linked immunosorbent assay. Whole-gut scintigraphy, GI symptom scores, and clinical features of SSc were compared between patients with and without antibodies. RESULTS Twenty of 88 (23%) patients had antivinculin antibodies, which were more prevalent in patients with slow gastric transit (35% versus 22%). In the univariate analyses, patients who were positive for antivinculin antibodies were more likely to have limited cutaneous disease (odds ratio [OR] 9.60 [95% confidence interval (95% CI) 1.19, 77.23]) and thyroid disease (OR 4.09 [95% CI 1.27, 13.21]). Such patients were also less likely to have lung involvement based on a Medsger Severity Score of ≥2 (OR 0.25 [95% CI 0.07, 0.92]). Higher levels of antivinculin autoantibodies were associated with less gastric emptying (β coefficient -3.41 [95% CI -6.72, -0.09]). The association between antivinculin antibodies and each of these clinical features remained significant in the multivariable model. In particular, the presence of antivinculin antibodies (β coefficient -6.20 [95% CI -12.33, -0.063]) and higher levels of antivinculin antibodies (β coefficient -3.64 [95% CI -7.05, -0.23]) were each significantly associated with slower gastric transit. CONCLUSION Antivinculin antibodies associate with slower gastric transit in SSc and may provide insight into GI complications of SSc.
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Affiliation(s)
| | | | - Jamie Perin
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | | | - Mark Pimentel
- Cedars-Sinai Medical Center, Los Angeles, California
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18
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Vitton V, Barthet M, Granel B, Gonzalez JM. Refractory GERD and systemic sclerosis: The end of a dead end? Clin Res Hepatol Gastroenterol 2023; 47:102140. [PMID: 37187259 DOI: 10.1016/j.clinre.2023.102140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 05/08/2023] [Accepted: 05/10/2023] [Indexed: 05/17/2023]
Affiliation(s)
- Véronique Vitton
- Service de Gastroentérologie, Hôpital NORD, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, France.
| | - Marc Barthet
- Service de Gastroentérologie, Hôpital NORD, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, France
| | - Brigitte Granel
- Service de médecine interne, Hôpital NORD, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, France
| | - Jean-Michel Gonzalez
- Service de Gastroentérologie, Hôpital NORD, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, France
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19
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Akbarzadeh R, Müller A, Humrich JY, Riemekasten G. When natural antibodies become pathogenic: autoantibodies targeted against G protein-coupled receptors in the pathogenesis of systemic sclerosis. Front Immunol 2023; 14:1213804. [PMID: 37359516 PMCID: PMC10285309 DOI: 10.3389/fimmu.2023.1213804] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
Systemic sclerosis (SSc) is a chronic, multisystem connective tissue, and autoimmune disease with the highest case-specific mortality and complications among rheumatic diseases. It is characterized by complex and variable features such as autoimmunity and inflammation, vasculopathy, and fibrosis, which pose challenges in understanding the pathogenesis of the disease. Among the large variety of autoantibodies (Abs) present in the sera of patients suffering from SSc, functionally active Abs against G protein-coupled receptors (GPCRs), the most abundant integral membrane proteins, have drawn much attention over the last decades. These Abs play an essential role in regulating the immune system, and their functions are dysregulated in diverse pathological conditions. Emerging evidence indicates that functional Abs targeting GPCRs, such as angiotensin II type 1 receptor (AT1R) and the endothelin-1 type A receptor (ETAR), are altered in SSc. These Abs are part of a network with several GPCR Abs, such as those directed to the chemokine receptors or coagulative thrombin receptors. In this review, we summarize the effects of Abs against GPCRs in SSc pathologies. Extending the knowledge on pathophysiological roles of Abs against GPCRs could provide insights into a better understanding of GPCR contribution to SSc pathogenesis and therefore help in developing potential therapeutic strategies that intervene with pathological functions of these receptors.
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20
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Korman BD, Lachant DJ, Castelino FV. Pulmonary Hypertension: How to Best Treat the Different Scleroderma Phenotypes? Rheum Dis Clin North Am 2023; 49:345-357. [PMID: 37028839 DOI: 10.1016/j.rdc.2023.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
Abstract
Pulmonary hypertension (PH) is a leading cause of morbidity and mortality in systemic sclerosis (SSc). PH is a heterogenous condition and several different forms of PH are associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to interstitial lung disease, PH due to left heart disease, and PH due to thromboembolic disease. Extensive research has led to an improved understanding of the mediators involved in the pathogenesis of SSc-PH. Initial combination therapy is the preferred treatment approach for SSc-PAH and requires coordinated care with a multidisciplinary team including rheumatology, pulmonology, and cardiology.
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Affiliation(s)
- Benjamin D Korman
- Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA.
| | - Daniel J Lachant
- Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 692, Rochester, NY 14642, USA
| | - Flavia V Castelino
- Division of Rheumatology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 4B, Boston, MA 02114, USA
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21
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Mormile I, Mosella F, Turco P, Napolitano F, de Paulis A, Rossi FW. Calcinosis Cutis and Calciphylaxis in Autoimmune Connective Tissue Diseases. Vaccines (Basel) 2023; 11:vaccines11050898. [PMID: 37243003 DOI: 10.3390/vaccines11050898] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/21/2023] [Accepted: 04/23/2023] [Indexed: 05/28/2023] Open
Abstract
Calcinosis represents a severe complication of several autoimmune disorders. Soft-tissue calcifications have been classified into five major types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Autoimmune diseases are usually associated with dystrophic calcifications, including calcinosis cutis, occurring in damaged or devitalized tissues in the presence of normal serum levels of calcium and phosphate. In particular, calcinosis cutis has been described in dermatomyositis, polymyositis, juvenile dermatomyositis, systemic sclerosis, systemic lupus erythematosus, primary Sjögren's syndrome, overlap syndrome, mixed connective tissue disease, and rheumatoid arthritis. Calciphylaxis, a severe and life-threatening syndrome presenting with vascular calcifications and thrombosis, has also been associated with some autoimmune conditions. Due to the potentially disabling character of calcinosis cutis and calciphylaxis, physicians' awareness about the clinical presentation and management of these diseases should be increased to select the most appropriate treatment option and avoid long-term complications. In this review, we aim to analyze the clinical features of calcinosis cutis and calciphylaxis associated with autoimmune diseases, and the main treatment strategies evaluated up to now for treating this potentially disabling disease.
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Affiliation(s)
- Ilaria Mormile
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Francesca Mosella
- Department of Plastic and Reconstructive Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Piergiorgio Turco
- Department of Plastic and Reconstructive Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Filomena Napolitano
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Amato de Paulis
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy
- WAO Center of Excellence, 80131 Naples, Italy
| | - Francesca Wanda Rossi
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy
- WAO Center of Excellence, 80131 Naples, Italy
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22
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Abstract
The upper gastrointestinal (GI) tract is frequently involved in systemic sclerosis (SSc) and may impact quality of life, physical function and survival. Although we are currently very proactive in terms of screening for heart and lung involvement, patients with SSc are not routinely screened for GI involvement. This review details the available investigations for common upper GI symptoms in SSc, including dysphagia, reflux and bloating and provides advice as to how to integrate these investigations into current clinical care.
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23
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Lee KA, Kim HJ, Kim HS. Comparison of predictive value of FRAX, trabecular bone score, and bone mineral density for vertebral fractures in systemic sclerosis: A cross-sectional study. Medicine (Baltimore) 2023; 102:e32580. [PMID: 36637920 PMCID: PMC9839281 DOI: 10.1097/md.0000000000032580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Assessing fracture risk is important for managing patients with systemic sclerosis (SSc). Vertebral fracture (VF) is the most common fracture and is associated with future VF and non-VF. We aimed to evaluate the predictive value of FRAX, trabecular bone score (TBS), and bone mineral density (BMD) for VFs, compared to rheumatoid arthritis (RA) patients and postmenopausal women, and to identify risk factors for VFs in SSc. In this cross-sectional study, prevalent VFs, 10-year probability of major osteoporotic fracture by FRAX (FRAX-MOF), TBS, and BMD were assessed in women with SSc (n = 69) and RA (n = 58), and postmenopausal women (n = 38). Risk factors for osteoporosis, modified Rodnan total skin score (mRSS), organ involvement, and patterns of nailfold capillaroscopy (NFC) were also evaluated. The accuracy of BMD (T-score ≤ -2.5), TBS and FRAX-MOF, with and without TBS adjustment, to detect prevalent VF was assessed by determining the area under the receiver operating characteristic (ROC) curve. Patients with SSc (14.5%) and RA (17.2%) had significantly more VFs than postmenopausal women (0%) (P = .031). Non-significant differences were observed in TBS and BMD of all groups. The FRAX-MOF were higher in RA (9.2%) than SSc group (6.1%) and postmenopausal women (5.5%) (P < .001). Based on the ROC curve, TBS-adjusted FRAX-MOF (0.803) showed largest area under curve (AUC) to detect the prevalent VFs, followed by FRAX-MOF (0.796), TBS (0.765), and BMD (0.588) in the SSc group. In the RA group, FRAX-MOF had the largest AUC (0.896), followed by TBS-adjusted FRAX-MOF (0.863), TBS (0.736), and BMD (0.686). The cutoffs for FRAX-MOF and TBS-adjusted FRAX-MOF for detecting VFs were 8.95% and 9.7% for SSc, and 14.5% and 14% for RA. No association between VFs and SSc subtypes, organ involvement, mRSS or NFC patterns was found. FRAX-MOF, with or without TBS, had better predictive value for VFs than BMD and TBS in SSc. However, FRAX-MOF underestimated the probability of VFs in SSc compared with RA.
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Affiliation(s)
- Kyung-Ann Lee
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul, South Korea
| | - Hyun-Joo Kim
- Department of Radiology, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul, South Korea
| | - Hyun-Sook Kim
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul, South Korea
- * Correspondence: Hyun-Sook Kim, Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, South Korea (e-mail: )
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Zhang X, Zhang H, Zhao J, Li Y, Wang H, Li C. Diagnostic accuracy and predictive value of autoantibody profiles in patients with systemic sclerosis: a single-center study. Clin Rheumatol 2023; 42:1297-1306. [PMID: 36604358 DOI: 10.1007/s10067-022-06487-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 12/10/2022] [Accepted: 12/12/2022] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To determine diagnostic accuracy and evaluate the predictive value of autoantibody profiles in patients with systemic sclerosis (SSc). METHODS A total of 140 patients with SSc (125 female, mean age 54.2 ± 14.2 years) were analyzed by a multiplex line immunoassay (Euroimmun) for autoantibodies against 12 SSc-related antigens. Associations between the presence of the autoantibodies and demographic clinical manifestations of patients with SSc were investigated. RESULTS The sensitivity and specificity of this assay were as follows: 32.9% and 99.4% for anti-Scl-70, 29.3% and 88.9% for anti-CENP A, 28.6% and 87.8% for anti-CENP B, 7.1% and 97.8% for anti-RP11, 5.7% and 100% for anti-RP155, 2.9% and 99.4% for anti-NOR 90, 2.9% and 98.9% for anti-Th/To, 1.4% and 96.7% for anti-PM-Scl-100, 5.0% and 98.3% for anti-PM-Scl-75, and 2.9% and 97.2% for anti-Ku, respectively. Anti-Scl-70 was significantly associated with sine scleroderma (P = 0.003), digital ulcers (P = 0.047), and Raynaud's phenomenon as the first clinical manifestation of onset (P = 0.017). SSc-ILD was more common in patients with anti-Scl-70 (P = 0.029) and less frequent in patients with anti-CENP A (P < 0.001) and anti-CENP B (P < 0.001). There was a significant association between PAH with anti-CENP A (P = 0.008) and anti-CENP B (P = 0.025). Renal involvement was significantly related to anti-NOR90 (P = 0.026) and anti-Th/To (P = 0.026). CONCLUSIONS This study confirmed the important role of autoantibodies in accurately diagnosing SSc. The autoimmune profile of patients with SSc was related to specific disease manifestations. Key Points • Autoantibody profiles were useful for diagnosing SSc and predicting clinical features of patients.
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Affiliation(s)
- Xiaoying Zhang
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Huijuan Zhang
- Department of Rheumatology, She Xian Hospital, Handan, Hebei Province, China
| | - Jing Zhao
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Yun Li
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Hongyan Wang
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Chun Li
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China.
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25
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Nassar M, Ghernautan V, Nso N, Nyabera A, Castillo FC, Tu W, Medina L, Ciobanu C, Alfishawy M, Rizzo V, Eskaros S, Mahdi M, Khalifa M, El-Kassas M. Gastrointestinal involvement in systemic sclerosis: An updated review. Medicine (Baltimore) 2022; 101:e31780. [PMID: 36397401 PMCID: PMC9666124 DOI: 10.1097/md.0000000000031780] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the highest incidence reported in people aged 44 to 55. Females are 5 times more likely than males to suffer from SSc. Morbidity and mortality rates associated with SSc are predominantly elevated among patients with GI manifestations. Esophageal and intestinal manifestations impact 90% and 40% to 70% of patients with systemic scleroderma, respectively. SSc patients are known to suffer from small bowel hypomotility and small intestinal bacterial overgrowth, which cause malabsorption and malnutrition, ultimately contributing to the 50% mortality rate. Fecal incontinence is a common symptom of SSc that can lead to depression. SSc patients may suffer from gastrointestinal complications that can negatively impact their quality of life on a daily basis. Multidisciplinary approaches are necessary for systematically managing gastrointestinal complications associated with SSc. A prospective study should focus on developing targeted therapies to improve recovery patterns and prognosis in cases of SSc. This article summarizes the epidemiology, commonly reported clinical manifestations, complications, and available treatments for treating GI pathology in SSc patients.
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Affiliation(s)
- Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Victoria Ghernautan
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Akwe Nyabera
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Francisco Cuevas Castillo
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Wan Tu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Luis Medina
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | | | - Mostafa Alfishawy
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Saphwat Eskaros
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health+Hospitals, Queens, NY, USA
| | - Mamdouh Mahdi
- Internal Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Khalifa
- Hospital Management Department, Helwan University, Cairo, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
- * Correspondence: Mohamed El-Kassas, Endemic Medicine Department, Faculty of Medicine, Helwan University, Ain Helwan 11795 Cairo, Egypt (e-mail: )
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Hughes M, Allanore Y, Baron M, Del Galdo F, Denton CP, Frech T, Furst DE, Galetti I, Dagna L, Herrick AL, Kuwana M, Matucci-Cerinic P, McMahan ZH, Murray CD, Proudman S, Matucci-Cerinic M. Proton pump inhibitors in systemic sclerosis: a reappraisal to optimise treatment of gastro-oesophageal reflux disease. THE LANCET. RHEUMATOLOGY 2022; 4:e795-e803. [PMID: 37936680 PMCID: PMC10628971 DOI: 10.1016/s2665-9913(22)00183-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2023]
Abstract
Gastroesophageal reflux disease (GERD) is associated with significant morbidity in patients with systemic sclerosis (SSc). Although the introduction of proton pump inhibitors (PPIs) into clinical care have represented a major achievement in the management of oesophago-gastric problems in SSc, PPIs are seldom fully effective in SSc patients, and the utilization of maximum PPI dosages is a very frequent clinical practice. However, currently there is little evidence currently to support the empiric use of PPIs in SSc which is especially relevant in regard to safety concerns of long-term exposure with have been raised in the general population. The purpose of this viewpoint is to highlight the significant beneficial impact of PPIs on GERD in SSc, while considering the potential adverse effects in this patient population. Furthermore, we highlight the unmet needs of SSc patients with GERD, and also propose an agenda for future research to optimise the safe and effective use of PPIs in SSc.
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Affiliation(s)
- Michael Hughes
- Tameside Hospital, Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne, United Kingdom
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom
| | - Yannick Allanore
- Service de Rhumatologie, Hôpital Cochin, APHP, Université de Paris, Paris, France
| | - Murray Baron
- Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Francesco Del Galdo
- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | - Christopher P Denton
- Centre for Rheumatology, Royal Free Campus, University College London, United Kingdom
| | - Tracy Frech
- Vanderbilt University Medical Center, Department of Medicine, Division of Rheumatology and Immunology, Nashville, TN, USA
| | - Daniel E Furst
- Department of Experimental and Clinical Medicine, University of Florence & Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy
- Division of Rheumatology, Department of Medicine, University of California in Los Angeles, Los Angeles, California, USA
| | - Ilaria Galetti
- FESCA, Federation of European Scleroderma Associations, Belgium
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Ariane L Herrick
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom
- Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Pietro Matucci-Cerinic
- University Hospital, Santa Maria della Misericordia, Department of Surgery and Transplantation, University of Udine, Italy
| | - Zsuzsanna H McMahan
- Johns Hopkins University School of Medicine, Department of Medicine, Division of Rheumatology, Baltimore, MD
| | - Charles D Murray
- Jewish General Hospital, Division of Rheumatology, McGill University, Montreal, Canada
| | - Susanna Proudman
- Rheumatology Unit, Royal Adelaide Hospital and Discipline of Medicine, University of Adelaide, Adelaide, South Australia, 5000
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
- Dept. Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy
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27
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Fiorentini E, Russo E, Amedei A, Bellando Randone S. Fecal microbiome in systemic sclerosis, in search for the best candidate for microbiota-targeted therapy for small intestinal bacterial overgrowth control. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:163-167. [PMID: 36211209 PMCID: PMC9537701 DOI: 10.1177/23971983221118871] [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: 04/22/2022] [Accepted: 07/10/2022] [Indexed: 10/03/2023]
Abstract
Gastrointestinal involvement is a common complication in systemic sclerosis patients and must be suspected and investigated already in the early stages of the disease. Gastrointestinal symptoms and complications-such as gastroesophageal reflux disease, intestinal pseudo-obstruction, malnutrition, diarrhea, constipation, and small intestinal bacterial overgrowth-severely impair systemic sclerosis patients' quality of life and affect their prognosis. Although some pathogenetic aspects of the gastrointestinal involvement in systemic sclerosis remain unclear, defining the characteristics of the microbiota and its role could help in risk stratification, selection of candidates for microbiota-targeted therapies, prediction of standard treatment efficacy, and prognosis of systemic sclerosis patients. Finally, understanding how to modify the microbiota composition may represent an important therapeutic approach to target gastrointestinal involvement in systemic sclerosis.
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Affiliation(s)
- Elisa Fiorentini
- Rheumatology Unit, Azienda Ospedaliero
Universitaria Careggi, Florence, Italy
| | - Edda Russo
- Department of Clinical and Experimental
Medicine, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Amedeo Amedei
- Department of Clinical and Experimental
Medicine, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
- SOD of Interdisciplinary Internal Medicine,
Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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28
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Hughes M, Harrison E, Herrick AL, McLaughlin JT, Lal S. The need to accurately measure energy intake and expenditure in patients with systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:217-223. [PMID: 36211201 PMCID: PMC9537710 DOI: 10.1177/23971983221095763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 04/01/2022] [Indexed: 10/03/2023]
Abstract
Background Malnutrition is common in systemic sclerosis and patients are frequently underweight. However, the balance between assessed dietary energy intake versus expenditure has been neglected to date. This study aimed to assess energy (dietary) intakes and expenditures and to compare discrepancies in systemic sclerosis. Methods Thirty-six outpatients with systemic sclerosis completed the study. Demographics and clinical data were recorded. Functional questionnaires were completed. Predicted energy requirements were calculated. Over a consecutive 3-day period, patients completed an estimated food diary and wore a specialist energy expenditure monitor (SenseWear® Armband). Assessments of intake and expenditure were compared for individual patients, and the impact according to patient demographics, clinical manifestations and disease severity evaluated. Results Energy intake did not correlate with predicted (s = 0.117; p = 0.511) or measured (s = -0.039; p = 0.825) expenditures. Predicted and measured energy expenditures correlated, but actual values differed for individuals (intraclass correlation = 0.62; 95% limits of agreement = -459 to 751 kcal). Respiratory involvement was negatively correlated with number of steps (s = -0.350; p = 0.04) and time spent lying (s = 0.333; p = 0.05). There was a significant correlation between body mass index and predicted versus measured energy discrepancy (s = 0.41; p = 0.02), and this discrepancy was greater with higher body mass indices. Conclusion There was no correlation between intake and either predicted or measured energy expenditure. Predicted and measured energy expenditures were strongly correlated yet differed for the individual patient. In patients with systemic sclerosis, where energy expenditure must be accurately assessed, it should be directly measured.
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Affiliation(s)
- Michael Hughes
- Department of Rheumatology, Tameside
and Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne, UK
- Division of Musculoskeletal and
Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of
Manchester & Salford Royal NHS Foundation Trust, Manchester, UK
| | | | - Ariane L Herrick
- Division of Musculoskeletal and
Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of
Manchester & Salford Royal NHS Foundation Trust, Manchester, UK
| | - John T McLaughlin
- Division of Diabetes, Endocrinology and
Gastroenterology, Faculty of Biology, Medicine and Health, The University of
Manchester & Salford Royal NHS Foundation Trust, Manchester, UK
| | - Simon Lal
- Division of Diabetes, Endocrinology and
Gastroenterology, Faculty of Biology, Medicine and Health, The University of
Manchester & Salford Royal NHS Foundation Trust, Manchester, UK
- Intestinal Failure Unit, Salford Care
Organisation, Salford Royal NHS Foundation Trust, Salford, UK
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29
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Chennakesavulu PV, Uppaluri S, Koyi J, Jhaveri S, Avanthika C, Sakhamuri LT, Ashokbhai PK, Singh P. Pulmonary Hypertension in Scleroderma- Evaluation and Management. Dis Mon 2022:101468. [PMID: 36163292 DOI: 10.1016/j.disamonth.2022.101468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Pulmonary Arterial Hypertension (PAH) is a clinical syndrome consisting of physiologic/hemodynamic criteria that are a consequence of several etiologies. Systemic Sclerosis (SSc), one of the most common causes of PAH, is an autoimmune disorder of the connective tissue leading to fibrosis that involves the skin, gastrointestinal tract, lungs, heart, kidney etc. SSc has an annual prevalence of one to five cases for every 1000 individuals and nearly 15 percent of all cases develop PAH. At its core, Pulmonary hypertension (PH) in SSc is an obliterative vasculopathy in small to medium-sized pulmonary arterioles. A host of other local and systemic mechanisms operate in concert to gradually alter the hemodynamics resulting in elevated pulmonary vascular resistance and thus right ventricular afterload. A diagnosis of PAH in SSc is virtually a death sentence, with studies reporting a mortality rate of 50 per cent in the 3 years of diagnosis. Therefore, developing and implementing a robust screening and diagnosis protocol is crucial in the fight against this pervasive disease. This review aims to summarize the current literature of PAH in SSc, with a special focus on the screening and diagnosis protocols, newer treatment options and prognostic indicators for the same.
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Affiliation(s)
| | - Srikar Uppaluri
- Kamineni Academy of medical sciences and research centre, Hyderabad, India.
| | | | | | | | | | | | - Priyanka Singh
- United health services hospital, Wilson medical center, New York
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30
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Li B, Yan J, Pu J, Tang J, Xu S, Wang X. A Response to: Letter to the Editor Regarding [Esophageal Dysfunction and Systemic Sclerosis: Drugs Should be Kept in Mind]. Rheumatol Ther 2022; 9:1241-1243. [PMID: 35716237 PMCID: PMC9314522 DOI: 10.1007/s40744-022-00458-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 04/26/2022] [Indexed: 11/17/2022] Open
Affiliation(s)
- Bo Li
- Department of Gastroenterology, Tongji Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
| | - Junqing Yan
- Department of Surgery Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
| | - Jincheng Pu
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
| | - Jianping Tang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
| | - Shuchang Xu
- Department of Gastroenterology, Tongji Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
| | - Xuan Wang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
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Chaves SDA, Puissant B, Porel T, Bories E, Adoue D, Alric L, Astudillo L, Huart A, Lairez O, Michaud M, Ribes D, Prévot G, Sailler L, Gaches F, Pugnet G. Clinical impact and prognosis of cryoglobulinemia and cryofibrinogenemia in systemic sclerosis. Autoimmun Rev 2022; 21:103133. [PMID: 35752439 DOI: 10.1016/j.autrev.2022.103133] [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: 05/14/2022] [Accepted: 06/07/2022] [Indexed: 11/24/2022]
Abstract
INTRODUCTION An association of systemic sclerosis (SSc) with cryoglobulin and/or cryofibrinogenemia has been described. However, clinical, biological, morphological and prognostic implications are unknown. The objective of this study was to describe the phenotype and evaluate the prognosis of cryoglobulinemia and/or cryofibrinogenemia in the progression of SSc. MATERIALS AND METHODS Patients were included from the Systemic Scleroderma Toulouse Cohort (SSTC), between June 1, 2005 and May 31, 2018, and underwent a measurement of a cryoglobulin and/or cryofibrinogen in immunology laboratory at the Toulouse University Hospital Center. Patients with and without cryoglobulinemia >50 mg/l and patients with and without cryofibrinogenemia were compared to identified the impact of cryoprcipitate on the phenotype. Mortality based on cryoprecipitate was explored. RESULTS 166 patients were included in the study. 43.3% and 46.6% had a cryoglobulinemia >50 mg/l and cryofibrinogenemia, respectively. Cryoglobulin >50 mg was not associated with microvascular damage. Cryoglobulin does not influence the phenotype. 5-and 10-years survival were 97.6% and 88.8% respectively in patients with cryoglobulinemia >50 mg/l versus 91.9% and 78.4% in patients without cryoglobulin>50 mg/l. 10-years survival was better for patients with cryoglobulinemia >50 mg/l (log-rank 0.0363). Cryofibrinogenemia was not associated with neoplasia, any clinical (in particular ischemic damage), biological or morphological features. Cryofibrinogenemia had no influence on the mortality of these patients. CONCLUSION Cryoglobulinemia and cryofibrinogenemia are frequent in SSc. The presence of cryoprecipitate (cryoglobulin or cryofibrinogen) not influence the phenotype and has not associated with a poor survival.
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Affiliation(s)
| | - Bénédicte Puissant
- Centre Hospitalier Universitaire, Laboratoire d'Immunologie, Toulouse, France
| | - Tiphaine Porel
- Centre Hospitalier Universitaire, Medecine Interne, Toulouse, France
| | - Eva Bories
- Centre Hospitalier Universitaire, Medecine Interne, Toulouse, France
| | - Daniel Adoue
- Centre Hospitalier Universitaire, Medecine Interne, Toulouse, France
| | - Laurent Alric
- Centre Hospitalier Universitaire, Medecine Interne, Toulouse, France
| | | | - Antoine Huart
- Centre Hospitalier Universitaire, Néphrologie, Toulouse, France
| | - Olivier Lairez
- Centre Hospitalier Universitaire, Cardiologie, Toulouse, France
| | - Martin Michaud
- Clinique Ambroise-Paré, Medecine Interne, Toulouse, France
| | - David Ribes
- Centre Hospitalier Universitaire, Néphrologie, Toulouse, France
| | - Grégoire Prévot
- Centre Hospitalier Universitaire, Pneumologie, Toulouse, France
| | - Laurent Sailler
- Centre Hospitalier Universitaire, Medecine Interne, Toulouse, France
| | - Francis Gaches
- Hopital Joseph Ducuing, Medecine Interne, Toulouse, France
| | - Gregory Pugnet
- Centre Hospitalier Universitaire, Medecine Interne, Toulouse, France; Centre Hospitalier Universitaire, Laboratoire d'Immunologie, Toulouse, France; Clinique Saint-Exupery, Medecine Interne, Toulouse, France; Centre Hospitalier Universitaire, Néphrologie, Toulouse, France; Centre Hospitalier Universitaire, Cardiologie, Toulouse, France; Clinique Ambroise-Paré, Medecine Interne, Toulouse, France; Centre Hospitalier Universitaire, Pneumologie, Toulouse, France; Hopital Joseph Ducuing, Medecine Interne, Toulouse, France; Centre D'investigation Clinique (CIC), 1436 PEPSS Team, Toulouse, France
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Bandini G, Cometi L, Accogli E, Domanico A, Tofani L, Bruni C, Bellando-Randone S, Lepri G, Orlandi M, Guiducci S, El-Aoufy K, Ciuti G, Fabbri A, Matucci-Cerinic M, Moggi-Pignone A. Ultrasound evaluation of bowel vasculopathy in systemic sclerosis. Eur J Intern Med 2022; 100:62-68. [PMID: 35058148 DOI: 10.1016/j.ejim.2022.01.026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/05/2022] [Accepted: 01/13/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement. OBJECTIVES To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls. METHODS The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded. RESULTS 28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p < 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p < 0.0001 - p adj <0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p < 0.0001 - p adj <0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p < 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p < 0.0001 - p adj <0.0001) in SSc patients than controls. CONCLUSION involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy.
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Affiliation(s)
- Giulia Bandini
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy.
| | - Laura Cometi
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Esterita Accogli
- Department of Internal Medicine, Centre of Research and Learning in Ultrasound, Maggiore Hospital, Bologna, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Andrea Domanico
- Department of Internal Medicine, Centre of Research and Learning in Ultrasound, Maggiore Hospital, Bologna, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Lorenzo Tofani
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Cosimo Bruni
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Silvia Bellando-Randone
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Gemma Lepri
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Martina Orlandi
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Serena Guiducci
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Khadija El-Aoufy
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Gabriele Ciuti
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Alessia Fabbri
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Alberto Moggi-Pignone
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
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Murphy SL, Berrocal VJ, Poole JL, Khanna D. Reliability, validity, and responsiveness to change of the Patient-Reported Outcomes Measurement Information System self-efficacy for managing chronic conditions measure in systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:110-116. [PMID: 35585951 PMCID: PMC9109504 DOI: 10.1177/23971983211049846] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/12/2021] [Indexed: 09/17/2023]
Abstract
Objective The aim of this study is to examine validity, reliability, and responsiveness to change of Patient-Reported Outcomes Measurement Information System Self-Efficacy for Managing Chronic Conditions in persons with systemic sclerosis. Methods We conducted a post hoc analysis of the Patient-Reported Outcomes Measurement Information System Self-Efficacy measure and other quality-of-life measures from systemic sclerosis participants from a 16-week randomized control trial. The trial compared an Internet-based self-management program to a control condition where participants were provided an educational book. All participants completed outcome measures at baseline and following the 16-week trial period. Results The mean age of participants was 53.7 years, 91% were female and systemic sclerosis subtype included 44.9% limited/sine and 43.1% diffuse; mean disease duration was 9.0 years. All self-efficacy subscales (Managing Emotions, Symptoms, Daily Activities, Social Interactions, and Medications/Treatment) demonstrated good internal consistency (.92-.96). All subscales showed statistically significant correlations with other validated measures of depressive symptoms and quality of life (.20-.86) but were not associated with satisfaction nor with appearance. The subscales appropriately discriminated between those with and without depressive symptoms and demonstrated responsiveness to change over the 16-week period for those who had a corresponding increase in reported quality of life. Conclusion The Patient-Reported Outcomes Measurement Information System Self-Efficacy measure is valid, reliable, and responsive to change for persons with systemic sclerosis.
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Affiliation(s)
- Susan L Murphy
- Department of Physical Medicine and
Rehabilitation, University of Michigan, Ann Arbor, MI, USA
- Geriatric Research, Education, and
Clinical Center (GRECC), VA Ann Arbor Health Care System, Ann Arbor, MI, USA
| | | | - Janet L Poole
- Occupational Therapy Graduate Program,
University of New Mexico, Albuquerque, NM, USA
| | - Dinesh Khanna
- Division of Rheumatology, Department of
Internal Medicine, University of Michigan, Ann Arbor, MI, USA
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Cheah JX, Khanna D, McMahan ZH. Management of scleroderma gastrointestinal disease: Lights and shadows. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:85-97. [PMID: 35585948 PMCID: PMC9109510 DOI: 10.1177/23971983221086343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
Gastrointestinal symptoms affect the great majority of patients with systemic sclerosis. Management of these complications is often challenging as any region of the gastrointestinal tract may be involved, and significant heterogeneity exists in clinical presentation, kinetics, and outcomes. Here, we highlight new findings relevant to the management of systemic sclerosis-related gastrointestinal disease (lights) and consider areas that we have yet to elucidate (shadows).
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Affiliation(s)
- Jenice X Cheah
- Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Dinesh Khanna
- Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA
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Bae SS, Pourzand L, Hyun Kim G, Villegas BE, Oh A, Furst DE, Goldin J, Tashkin DP. The disconnect between visual assessment of air trapping and lung physiology for assessment of small airway disease in scleroderma-related interstitial lung disease: An observation from the Scleroderma Lung Study II Cohort. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:117-127. [PMID: 35585954 PMCID: PMC9109505 DOI: 10.1177/23971983211047160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/26/2021] [Indexed: 08/07/2023]
Abstract
OBJECTIVE To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. METHODS Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. RESULTS A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. CONCLUSION We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.
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Affiliation(s)
- Sangmee Sharon Bae
- Department of Medicine, Rheumatology,
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA, USA
| | - Lila Pourzand
- Department of Radiological Sciences,
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA, USA
| | - Grace Hyun Kim
- Department of Radiological Sciences,
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA, USA
| | - Bianca E Villegas
- Department of Radiological Sciences,
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA, USA
| | - Andrea Oh
- Department of Radiology, National
Jewish Health, Denver, CO, USA
| | - Daniel E Furst
- Department of Medicine, Rheumatology,
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA, USA
- University of Washington, Seattle, WA,
USA
- University of Florence, Florence,
Italy
| | - Jonathan Goldin
- Department of Radiological Sciences,
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA, USA
| | - Donald P Tashkin
- Department of Medicine, Pulmonary &
Critical Care, David Geffen School of Medicine, University of California, Los
Angeles, Los Angeles, CA, USA
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McMahan ZH, Tucker AE, Perin J, Volkmann ER, Kulkarni S, Ziessman HA, Pasricha PJ, Wigley FM. Relationship Between Gastrointestinal Transit, Medsger Gastrointestinal Severity, and University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 Symptoms in Patients With Systemic Sclerosis. Arthritis Care Res (Hoboken) 2022; 74:442-450. [PMID: 33064934 PMCID: PMC8050123 DOI: 10.1002/acr.24488] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 09/22/2020] [Accepted: 10/13/2020] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Systemic sclerosis (SSc)-associated gastrointestinal (GI) complications are attributed to a variety of factors, including diet, microbiota dysbiosis, or GI transit abnormalities. Our objective was to examine the contribution of abnormal GI transit to SSc Medsger GI severity scores and/or University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA GIT) 2.0 symptoms. METHODS Patients with SSc and GI symptoms (n = 71) and healthy controls (n = 18) underwent whole gut transit (WGT) scintigraphy to assess transit from the esophagus to the colon. The presence of delayed transit and percent emptying in each GI region were measured. We compared the WGT measurements between categories of the Medsger GI severity score (0-4) and across UCLA GIT 2.0 domains and total score (0-3). RESULTS A total of 88% of patients had >1 abnormal region of the gut on WGT scintigraphy. All patients requiring total parenteral nutrition had delayed small bowel transit, compared to only approximately 11% of patients in other Medsger GI severity groups (P ≤ 0.01). Severe colonic transit delays were more likely in patients with Medsger GI scores of 3 (pseudo-obstruction and/or malabsorption) compared to other Medsger GI groups (P = 0.02). Seventy-percent of these patients had ≤30% colonic emptying at 72 hours. Modest associations were noted between gastroesophageal reflux disease symptoms and delayed esophageal (r = -0.31, P = 0.05) and gastric emptying (r = -0.32, P = 0.05). CONCLUSION These data are important in providing evidence that SSc bowel disease affects transit of GI content and that delay in transit accounts in part for both bowel symptoms and Medsger GI severity. Prospective studies examining the benefit of early therapeutic intervention targeting GI transit abnormalities in patients at high risk for severe GI complications are needed.
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Affiliation(s)
| | - Ana E Tucker
- Johns Hopkins Bayview Medical Center, Baltimore, Maryland
| | - Jamie Perin
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
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Shirai Y, Kawami N, Iwakiri K, Kuwana M. Use of vonoprazan, a novel potassium-competitive acid blocker, for the treatment of proton pump inhibitor-refractory reflux esophagitis in patients with systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:57-61. [PMID: 35386943 PMCID: PMC8922677 DOI: 10.1177/23971983211021747] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/09/2021] [Indexed: 02/03/2023]
Abstract
Objective Proton pump inhibitor-refractory reflux esophagitis is one of the intractable conditions of systemic sclerosis for which new treatments are required. Vonoprazan is a novel potassium-competitive acid blocker and has been shown to have several advantages over conventional proton pump inhibitors, including a long duration of gastric acid suppression. Methods To investigate the efficacy of vonoprazan for treating proton pump inhibitor-refractory reflux esophagitis in patients with systemic sclerosis, 10 patients with proton pump inhibitor-refractory reflux esophagitis who were switched to vonoprazan were selected from our systemic sclerosis database. Reflux esophagitis was evaluated by endoscopy, and gastroesophageal reflux disease-related symptoms were assessed by the frequency scale for the symptoms of gastroesophageal reflux disease questionnaire before and after switching from proton pump inhibitor to vonoprazan at an average interval of 3.5 [2-5.5] months. Results After switching patients to vonoprazan, the endoscopic findings of reflux esophagitis were significantly improved (p = .033), and six patients (60%) achieved mucosal healing. The total frequency scale for the symptoms of gastroesophageal reflux disease score was also significantly decreased (p = .043), mainly by improving the acid reflux score. Vonoprazan was well tolerated and was continued for 15.5 [11.25-23.75] months in all patients. Conclusion Vonoprazan is a potential treatment option for treating proton pump inhibitor-refractory reflux esophagitis in systemic sclerosis patients.
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Affiliation(s)
- Yuichiro Shirai
- Department of Allergy and Rheumatology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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Acute exacerbation of interstitial lung disease associated with rheumatic disease. Nat Rev Rheumatol 2022; 18:85-96. [PMID: 34876670 DOI: 10.1038/s41584-021-00721-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/10/2021] [Indexed: 11/09/2022]
Abstract
Interstitial lung disease (ILD) is a cause of morbidity and mortality in patients with rheumatic diseases, such as connective-tissue diseases, rheumatoid arthritis and systemic vasculitis. Some patients with ILD secondary to rheumatic disease (RD-ILD) experience acute exacerbations, with sudden ILD progression and high mortality during or immediately after the exacerbation, and a very low 1-year survival rate. In the ILD subtype idiopathic pulmonary fibrosis (IPF), an acute exacerbation is defined as acute worsening or development of dyspnoea associated with new bilateral ground-glass opacities and/or consolidations at high-resolution CT, superimposed on a background pattern consistent with fibrosing ILD. However, acute exacerbation in RD-ILD (AE-RD-ILD) currently has no specific definition. The aetiology and pathogenesis of AE-RD-ILD remain unclear, but distinct triggers might include infection, mechanical stress, microaspiration and DMARD treatment. At this time, no effective evidence-based therapeutic strategies for AE-RD-ILD are available. In clinical practice, AE-RD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. In this Review, we summarize the clinical features, diagnosis, management and prognosis of AE-RD-ILD, enabling the similarities and differences with acute exacerbation in IPF to be critically assessed.
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Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review. J Immunol Res 2021; 2021:9782994. [PMID: 34881335 PMCID: PMC8648450 DOI: 10.1155/2021/9782994] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/29/2021] [Indexed: 01/11/2023] Open
Abstract
Background Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. Aim This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings. Methods and Results A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles. Conclusions Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients.
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De Almeida Chaves S, Porel T, Mounié M, Alric L, Astudillo L, Huart A, Lairez O, Michaud M, Prévot G, Ribes D, Sailler L, Gaches F, Adoue D, Pugnet G. Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality. Arthritis Res Ther 2021; 23:295. [PMID: 34876194 PMCID: PMC8650544 DOI: 10.1186/s13075-021-02672-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 11/08/2021] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature. OBJECTIVE To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc patients. METHODS A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed. RESULTS Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46-1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p=0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012), and the fact of being male (HR=3.25; p=0.0004). CONCLUSION Long-term data confirmed high mortality of SSc. Male sex, DLCO <70%, cardiac involvement, and CRP> 5mg/l were identified as independent predictors of mortality.
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Affiliation(s)
| | - Tiphaine Porel
- Department of Internal Medicine, CHU Toulouse, Toulouse, Midi-Pyrénées, France
| | - Mickael Mounié
- INSERM UMR1027, 37 Allées Jules Guesdes, Toulouse, Midi-Pyrénées, France
| | - Laurent Alric
- Department of Internal Medicine, CHU Toulouse, Toulouse, Midi-Pyrénées, France
- Universite Toulouse III Paul Sabatier Toulouse, Occitanie, France
| | - Léonardo Astudillo
- Department of Internal Medicine, Saint Exupéry Nephrology Clinic, Toulouse, Midi-Pyrénées, France
| | - Antoine Huart
- Department of Nephrology, CHU Toulouse, Toulouse, Midi-Pyrénées, France
| | - Olivier Lairez
- Universite Toulouse III Paul Sabatier Toulouse, Occitanie, France
- Department of Cardiology, CHU Toulouse, Toulouse, Midi-Pyrénées, France
| | - Martin Michaud
- Department of Internal Medicine, Hospital Joseph Ducuing, Toulouse, France
| | - Grégoire Prévot
- Department of Pneumology, CHU Toulouse, Toulouse, Midi-Pyrénées, France
| | - David Ribes
- Department of Nephrology, CHU Toulouse, Toulouse, Midi-Pyrénées, France
| | - Laurent Sailler
- Department of Internal Medicine, CHU Toulouse, Toulouse, Midi-Pyrénées, France
- Universite Toulouse III Paul Sabatier Toulouse, Occitanie, France
| | - Francis Gaches
- Department of Internal Medicine, Hospital Joseph Ducuing, Toulouse, France
| | - Daniel Adoue
- Department of Internal Medicine, CHU Toulouse, Toulouse, Midi-Pyrénées, France
- Universite Toulouse III Paul Sabatier Toulouse, Occitanie, France
| | - Gregory Pugnet
- Department of Internal Medicine, CHU Toulouse, Toulouse, Midi-Pyrénées, France
- Universite Toulouse III Paul Sabatier Toulouse, Occitanie, France
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Lee TH, Lee JS, Park S, Lee KA, Kim HS. Reliability and validity of the Korean version of the University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract instrument in patients with systemic sclerosis. Korean J Intern Med 2021; 36:1504-1514. [PMID: 33561335 PMCID: PMC8588985 DOI: 10.3904/kjim.2020.190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/08/2020] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND/AIMS Systemic sclerosis (SSc) is associated with a wide range of gastrointestinal (GI) changes. The University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) instrument is a self-administered GI assessment instrument for patients with SSc. We developed a Korean version of the UCLA SCTC GIT 2.0 instrument and evaluated its reliability and internal consistency. METHODS The participants were 37 Korean patients with SSc. Translation and cross-cultural adaptation of the UCLA SCTC GIT 2.0 were performed according to international standardized guidelines. We evaluated reproducibility by calculating the intraclass correlation coefficients and assessed the internal consistency of the Korean version of the UCLA SCTC GIT 2.0. We assessed its construct validity by evaluating its correlations with the Short Form Health Survey version 2 and EQ-5D scores by means of Spearman correlation analyses. RESULTS Patients with SSc were mostly women (89.19%) with a mean age of 52.2 years, median disease duration of 24 months, and median modified Rodnan total skin score of 4. The median total GIT score on the UCLA SCTC GIT 2.0 was 0.3. The UCLA SCTC GIT 2.0 Korean version showed excellent internal consistency (Cronbach's α of total GIT score = 0.863). Most domains of the ULCA SCTC GIT 2.0 were correlated with those of the EuroQol (EQ)-5D score. CONCLUSION The Korean version of the UCLA SCTC GIT 2.0 has acceptable internal consistency, reliability, and validity. Therefore, it can be used to assess GIT involvement in Korean patients with SSc.
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Affiliation(s)
- Tae Hee Lee
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Joon Seong Lee
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Suyeon Park
- Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea
- Department of Applied Statistics, Chung-Ang University, Seoul, Korea
| | - Kyung-Ann Lee
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Hyun-Sook Kim
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
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Mugo GW, Murunga EM. Systemic sclerosis manifesting as intractable gastro-oesophageal reflux and diarrhoea: a case report from Kenya. Pan Afr Med J 2021; 39:225. [PMID: 34630837 PMCID: PMC8486939 DOI: 10.11604/pamj.2021.39.225.29771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/15/2021] [Indexed: 11/11/2022] Open
Abstract
Systemic sclerosis is a rare condition that has not been well reported in Africa, and several multisystemic manifestations, including gastrointestinal ones, have not been well documented locally. We present an unusual case of persistent gastro-oesophageal reflux and diarrhoea in a 74-year-old Kenyan female, who progressively developed abdominal distention, dysphagia and Raynaud´s phenomenon. Stool tests were unremarkable, whereas antinuclear antibody, ribonucleoproteins antibody (anti-nRNP/Sm) and anti-Sjögren's-syndrome-related antigen A autoantibody (anti-SSA) tests were positive. Endoscopic and imaging investigations revealed features of gastrointestinal dysmotility including reflux oesophagitis, gastroparesis and chronic intestinal pseudo-obstruction. A diagnosis of systemic sclerosis was made, and she responded well to medical treatment. We present this case to contribute to the limited literature of a disease associated with high morbidity and mortality, as well as encourage fellow clinicians to have a high level of suspicion in their differentials of persistent gastrointestinal dysmotility.
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Suliman YA, Kafaja S, Alemam M, Shaweesh Y, Tavakoli K, Furst DE. Responsiveness of the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract 2.0 (UCLA-SCTC-GIT 2.0)to change in scleroderma patients. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2021; 6:236-241. [PMID: 35387210 PMCID: PMC8922669 DOI: 10.1177/2397198321992197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/10/2020] [Indexed: 01/22/2024]
Abstract
INTRODUCTION Gastrointestinal tract involvement in systemic sclerosis is the most common internal organ involvement. Among the few validated patient-reported outcome measures for gastrointestinal involvement are the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract 2.0 (UCLA-GIT 2.0) and the gastrointestinal problems' visual analog scale (SHAQ-VAS). The latter is a component of the Scleroderma Health Assessment Questionnaire Disability Index. Our aim is to compare the responsiveness of the UCLA-GIT 2.0 total score, single domains, upper and lower gastrointestinal domains, and gastrointestinal problems' visual analog scale of the scleroderma HAQ(SHAQ-GI-VAS) to change in gastrointestinal medication. In addition, we evaluated the correlation between the UCLA-GIT 2.0 and SHAQ-GI-VAS scale in our systemic sclerosis population. METHODS One hundred fifteen systemic sclerosis patients attending the University of California Los Angeles and Seattle outpatient clinics with two or more consecutive visits were enrolled in our study. The UCLA-GIT 2.0 and SHAQ_VAS were completed by all patients at both visits; any change in gastrointestinal medication at the baseline visit was reported. UCLA-GIT 2.0 asks about how the gastrointestinal tract affects the patient over the last week; It consists of 34 questions in seven domains (reflux, distension, soilage, diarrhea, social function, emotional wellbeing, and constipation). THE SHAQ-GI-VAS is a 100-mm horizontal VAS that asks the patient; "In the past week, how much did your gastrointestinal symptoms interfere with your function". These measures were evaluated at two consecutive visits. Any change in gastrointestinal medication at baseline visit was reported. Percent change was calculated to evaluate the change in the values of the UCLA-GIT 2.0 and the SHAQ_GI-VAS, and we dichotomized the patients into two groups according to whether there was a change in gastrointestinal treatment or not. Pearson correlation was used to correlate both tests at baseline. RESULTS Ninety-eight (85%) of the systemic sclerosis patients were females, mean age: 52 years (standard deviation ± 12.9); median disease duration: 7 (range: 4-11 years), diffuse subtype: 57 patients (50%), median baseline gastrointestinal tract 2.0 was 0.3 (0.1-0.7) and median baseline SHAQ-GI-VAS was 0.8 (0-4.1). Out of the 115 patients, 41 (37.0%) patients needed a change in gastrointestinal medication at baseline visit (Group 1); they were compared to those not changing gastrointestinal medications (Group 2). Responsiveness to gastrointestinal medication treatment change in the form of percent change in total UCLA-GIT 2.0 was significantly more in Group 1 than in Group 2 (-6.6 (standard deviation = 20) in Group 1 vs +6.9 (standard deviation ± 18.8) in Group 2, p value < 0.001). On the contrary, there was no statistically significant difference between percent changes in SHAQ-GI-VAS from the in Group 1 versus Group 2 (59.5 (standard deviation ± 172) in Group 1 vs 51.9 (standard deviation ± 126.4) in Group 2, p value = 0.816). The correlation between the UCLA-GIT 2.0 and the SHAQ_GI-VAS was moderate (r = 0.6). CONCLUSION The University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract 2.0 and gastrointestinal problems' visual analog scale are utilized to measure gastrointestinal tract involvement in systemic sclerosis. Unlike the gastrointestinal problems' visual analog scale, the gastrointestinal tract 2.0 was responsive to change in gastrointestinal medication while the SHAQ-GI-VAS was not. Hence, the UCLA-GIT 2.0 could be utilized in future trials and observational studies as a measure of systemic sclerosis gastrointestinal responsiveness.
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Affiliation(s)
- Yossra Atef Suliman
- Division of Rheumatology, Department of
Internal Medicine, University of California Los Angeles, David Geffen School of
Medicine, Los Angeles, CA, USA
- Rheumatology and Rehabilitation
Department, Assiut University Hospital, Assiut, Egypt
| | - Suzanne Kafaja
- Division of Rheumatology, Department of
Internal Medicine, University of California Los Angeles, David Geffen School of
Medicine, Los Angeles, CA, USA
| | - Mohamed Alemam
- Clinical Pathology and Laboratory
Medicine Department, Qena Faculty of Medicine, South Valley University, Qena,
Egypt
| | - Yasser Shaweesh
- Division of Rheumatology, Department of
Internal Medicine, University of California Los Angeles, David Geffen School of
Medicine, Los Angeles, CA, USA
| | - Kasra Tavakoli
- Division of Rheumatology, Department of
Internal Medicine, University of California Los Angeles, David Geffen School of
Medicine, Los Angeles, CA, USA
| | - Daniel E Furst
- Division of Rheumatology, Department of
Internal Medicine, University of California Los Angeles, David Geffen School of
Medicine, Los Angeles, CA, USA
- University of Florence, Florence,
Italy
- University of Washington, Seattle, WA,
USA
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Zawatsky CN, Park JK, Abdalla J, Kunos G, Iyer MR, Cinar R. Peripheral Hybrid CB 1R and iNOS Antagonist MRI-1867 Displays Anti-Fibrotic Efficacy in Bleomycin-Induced Skin Fibrosis. Front Endocrinol (Lausanne) 2021; 12:744857. [PMID: 34650521 PMCID: PMC8505776 DOI: 10.3389/fendo.2021.744857] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 09/09/2021] [Indexed: 12/16/2022] Open
Abstract
Scleroderma, or systemic sclerosis, is a multi-organ connective tissue disease resulting in fibrosis of the skin, heart, and lungs with no effective treatment. Endocannabinoids acting via cannabinoid-1 receptors (CB1R) and increased activity of inducible NO synthase (iNOS) promote tissue fibrosis including skin fibrosis, and joint targeting of these pathways may improve therapeutic efficacy. Recently, we showed that in mouse models of liver, lung and kidney fibrosis, treatment with a peripherally restricted hybrid CB1R/iNOS inhibitor (MRI-1867) yields greater anti-fibrotic efficacy than inhibiting either target alone. Here, we evaluated the therapeutic efficacy of MRI-1867 in bleomycin-induced skin fibrosis. Skin fibrosis was induced in C57BL/6J (B6) and Mdr1a/b-Bcrp triple knock-out (KO) mice by daily subcutaneous injections of bleomycin (2 IU/100 µL) for 28 days. Starting on day 15, mice were treated for 2 weeks with daily oral gavage of vehicle or MRI-1867. Skin levels of MRI-1867 and endocannabinoids were measured by mass spectrometry to assess target exposure and engagement by MRI-1867. Fibrosis was characterized histologically by dermal thickening and biochemically by hydroxyproline content. We also evaluated the potential increase of drug-efflux associated ABC transporters by bleomycin in skin fibrosis, which could affect target exposure to test compounds, as reported in bleomycin-induced lung fibrosis. Bleomycin-induced skin fibrosis was comparable in B6 and Mdr1a/b-Bcrp KO mice. However, the skin level of MRI-1867, an MDR1 substrate, was dramatically lower in B6 mice (0.023 µM) than in Mdr1a/b-Bcrp KO mice (8.8 µM) due to a bleomycin-induced increase in efflux activity of MDR1 in fibrotic skin. Furthermore, the endocannabinoids anandamide and 2-arachidonylglycerol were elevated 2-4-fold in the fibrotic vs. control skin in both mouse strains. MRI-1867 treatment attenuated bleomycin-induced established skin fibrosis and the associated increase in endocannabinoids in Mdr1a/b-Bcrp KO mice but not in B6 mice. We conclude that combined inhibition of CB1R and iNOS is an effective anti-fibrotic strategy for scleroderma. As bleomycin induces an artifact in testing antifibrotic drug candidates that are substrates of drug-efflux transporters, using Mdr1a/b-Bcrp KO mice for preclinical testing of such compounds avoids this pitfall.
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Affiliation(s)
- Charles N. Zawatsky
- Section on Fibrotic Disorders, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
| | - Joshua K. Park
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
| | - Jasmina Abdalla
- Section on Fibrotic Disorders, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
| | - George Kunos
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
| | - Malliga R. Iyer
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
- Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
| | - Resat Cinar
- Section on Fibrotic Disorders, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
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Lung Transplantation in Systemic Sclerosis: a Practice Survey of United States Lung Transplant Centers. Transplant Direct 2021; 7:e757. [PMID: 34514112 PMCID: PMC8425834 DOI: 10.1097/txd.0000000000001209] [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: 06/01/2021] [Revised: 06/17/2021] [Accepted: 07/03/2021] [Indexed: 11/27/2022] Open
Abstract
Supplemental Digital Content is available in the text. Lung transplantation in patients with systemic sclerosis (SSc) can be complicated by extrapulmonary manifestations of the disease, leading to concerns regarding posttransplant complications and outcomes.
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46
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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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47
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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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48
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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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Levin D, De Palma G, Zou H, Bazzaz AHZ, Verdu E, Baker B, Pinto-Sanchez MI, Khalidi N, Larché MJ, Beattie KA, Bercik P. Fecal microbiome differs between patients with systemic sclerosis with and without small intestinal bacterial overgrowth. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2021; 6:290-298. [PMID: 35382497 PMCID: PMC8922657 DOI: 10.1177/23971983211032808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 06/24/2021] [Indexed: 01/04/2023]
Abstract
Introduction: Gastrointestinal manifestations of systemic sclerosis affect up to 90% of
patients, with symptoms including diarrhea and constipation. Small
intestinal bacterial overgrowth is a condition associated with increased
numbers of pathogenic bacteria in the small bowel. While currently unknown,
it has been suggested that dysregulation of the fecal microbiota may play a
role in the development of systemic sclerosis and small intestinal bacterial
overgrowth. Objectives: Our study aimed to describe the fecal microbiota of patients with systemic
sclerosis and compare it between those with and without a diagnosis of small
intestinal bacterial overgrowth. We also compared the fecal microbiota of
systemic sclerosis patients with that of healthy controls to understand the
association between particular bacterial taxa and clinical gastrointestinal
manifestations of systemic sclerosis. Methods: A total of 29 patients with systemic sclerosis underwent breath testing to
assess for small intestinal bacterial overgrowth, provided stool samples to
determine taxonomic assignments, and completed the University of California
Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract
2.0, which details symptoms and quality-of-life factors. Stool samples were
compared between systemic sclerosis patients with and without small
intestinal bacterial overgrowth, and between patients with systemic
sclerosis and a healthy control cohort (n = 20), aged 18–80 years. Results: Fecal microbiome analyses demonstrated differences between systemic sclerosis
patients with and without small intestinal bacterial overgrowth and
differences in the diversity of species between healthy controls and
patients with systemic sclerosis. Trends were also observed in
anticentromere antibody systemic sclerosis patients, including higher
Alistipies indistincus spp. levels associated with
increased methane levels of breath gas testing and higher
Slakia spp. levels associated with increased rates of
fecal soiling. Conclusions: Our results suggest that changes to the fecal microbiome occur in patients
with small intestinal bacterial overgrowth and systemic sclerosis when
compared to healthy controls. As a cross-sectional study, the potential
pathophysiologic role of an altered microbiome in the development of
systemic sclerosis was not considered and hence needs to be further
investigated.
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Affiliation(s)
- Daniel Levin
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Giada De Palma
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Hannah Zou
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | | | - Elena Verdu
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Barbara Baker
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | | | - Nader Khalidi
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Maggie J Larché
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Karen A. Beattie
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Premysl Bercik
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
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50
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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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