Clinical Correlates of CENP-A and CENP-B Antibodies in a Large Cohort of Patients with Systemic Sclerosis

Objective.To study the clinical phenotypes of centromeric proteins (CENP)-A- and CENP-B-positive patients with systemic sclerosis (SSc) and to compare them to anticentromere antibody (ACA)-positive and negative SSc patients.Methods.Sera samples were collected from 802 patients with SSc enrolled in a multicenter cohort study. Antibodies to CENP-A and B were detected by ELISA, and ACA by indirect immunofluorescence. Associations with clinical and other serological manifestations of SSc were investigated.Results.CENP-A antibodies were detected in 276 (34%), CENP-B in 286 (36%), and ACA in 279 (35%) patients. Patients having ACA, CENP-A, and/or CENP-B resembled each other and differed from the remainder of the cohort in the following respects: older chronologically and at disease onset; more commonly women; more likely to have limited disease and lower skin scores; less likely to have finger ulcers, digital tuft resorption, or finger contractures; more likely to have pulmonary hypertension; less likely to have interstitial lung disease, scleroderma renal crisis, inflammatory arthritis, and inflammatory myositis; and having lower overall disease severity. CENP-A and/or B status was predictive of the extent of skin involvement over time. Patients with limited disease who were CENP-A-negative at baseline were more likely to progress to diffuse disease compared to CENP-A-positive patients (OR 2.55, 95% CI 1.37, 4.85, p = 0.004).Conclusion.Clinical immunology laboratories are increasingly using high-throughput ELISA tests for CENP antibodies, with or without ACA detected by indirect immunofluorescence. The phenotype of CENP-A and/or B-positive patients is generally similar to that associated with ACA.

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Clinical and serological characteristics of systemic sclerosis: Experience of a tertiary care center in Pakistan

Archives of Rheumatology ◽

10.46497/archrheumatol.2021.8701 ◽

2021 ◽

Vol 36 (4) ◽

pp. 587-594

Author(s):

Sadia Asif ◽

Asadullah Khan ◽

Muhammad Faiq ◽

Zia Ud Din ◽

Sarmad Zahoor ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Function Tests ◽

Care Center ◽

Tertiary Care ◽

Disease Onset ◽

Clinical Feature ◽

Digital Ulcers ◽

Limited Disease ◽

Raynaud Phenomenon ◽

Diffuse Disease

Objectives: This study aims to evaluate the clinical and serological characteristics of systemic sclerosis (SSc) in Pakistani population. Patients and methods: This prospective, cross-sectional study included a total of 38 patients (6 males, 32 females; mean age: 34.5±1.5 years; range, 16 to 60 years) with SSc who were admitted to our rheumatology clinic between November 2019 and January 2020. We evaluated the clinical, serological, and radiological features of SSc patients. Results: Thirty-four (89.5%) patients developed Raynaud phenomenon at the time of disease onset, while sclerodactyly was found in 34 (89.5%), digital ulcers in 25 (65.8%), and tendon friction rub in 12 (31.6%) patients. Interstitial lung disease was present in 30 (78.9%) patients with a higher prevalence in diffuse scleroderma (100%) than in limited scleroderma (70%) (p=0.01). Pulmonary hypertension was present in 18 patients with a significantly higher prevalence in diffuse disease (57.1%) than limited disease (11.8%) (p<0.01). Thirty (78.9%) patients had impaired pulmonary function tests. Fibromyalgia was present in seven (18.4%) patients, and depression was present in 10 (26.3%) patients. Antinuclear antibody (ANA) was positive in 30 (78.9%) patients. Anti-Scl-70 antibodies were present in 24 (63.2%) patients with a significant association with diffuse disease (85% vs. 35.3%, respectively; p<0.01). The anti-centromere antibodies (ACA) were present in 20 (52.6%) patients with a significantly higher rate in limited disease (94.2% vs. 19.0%, respectively; p<0.01). Conclusion: Scleroderma has a female preponderance. Raynaud phenomenon is the most initial clinical feature followed by other manifestations of a variable course and disease severity.

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The Association Between Disease Activity and Duration in Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.090919 ◽

2010 ◽

Vol 37 (11) ◽

pp. 2299-2306 ◽

Cited By ~ 7

Author(s):

JENNIFER G. WALKER ◽

RUSSELL J. STEELE ◽

MIREILLE SCHNITZER ◽

SUZANNE TAILLEFER ◽

MURRAY BARON ◽

...

Keyword(s):

Systemic Sclerosis ◽

Disease Activity ◽

Disease Duration ◽

Activity Index ◽

Disease Onset ◽

Depression Scale ◽

Disease Activity Index ◽

Cross Sectional ◽

Diffuse Disease ◽

Patient Reported

Objective.The absence of a standardized disease activity index has been an important barrier in systemic sclerosis (SSc) research. We applied the newly derived Valentini Scleroderma Disease Activity Index (SDAI) among our cohort of patients with SSc to document changes in disease activity over time and to assess possible differences in activity between limited and diffuse disease.Methods.Cross-sectional study of a national cohort of patients enrolled in the Canadian Scleroderma Research Group Registry. Disease activity was measured using the SDAI. Depression scores were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D).Results.A total of 326 out of 639 patients had complete datasets at the time of this analysis; 87% were female, of mean age 55.6 years, with mean disease duration 14.1 years. SDAI declined steeply in the first 5 years after disease onset and patients with diffuse disease had 42% higher SDAI scores than patients with limited disease with the same disease duration and depression scores (standardized relative risk 1.42, 95% CI 1.21, 1.65). Patients with higher CES-D scores had higher SDAI scores relative to patients with the same disease duration and disease subset (standardized RR 1.22, 95% CI 1.14, 1.31). Among the 10 components that make up the SDAI, only skin score (standardized OR 0.59, 95% CI 0.43, 0.82) and patient-reported change in skin (standardized OR 0.64, 95% CI 0.45, 0.92) decreased with increasing disease duration. High skin scores (standardized OR 32.2, 95% CI 15.8, 72.0) were more likely and scleredema (standardized OR 0.58, 95% CI 0.37, 0.92) was less likely to be present in patients with diffuse disease. High depression scores were associated with positive responses for patient-reported changes in skin and cardiopulmonary function.Conclusion.Disease activity declined with time and patients with diffuse disease had consistently higher SDAI scores. Depression was found to be associated with higher patient activity scores and strongly associated with patient self-response questions. The role of depression should be carefully considered in future applications of the SDAI, particularly as several components of the score rely upon patient recall.

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AB0093 CLINICAL AND SEROLOGICAL CHARACTERISTICS OF SYSTEMIC SCLEROSIS: EXPERIENCE FROM A TERTIARY CARE CENTER IN PAKISTAN

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1635 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1075.2-1076

Author(s):

S. Asif ◽

M. Haroon ◽

A. Khan ◽

M. Faiq

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Memorial Hospital ◽

Limited Disease ◽

Raynaud Phenomenon ◽

Female Ratio ◽

Diffuse Disease ◽

Gi Symptoms

Background:Systemic sclerosis (SS) is less studied Connective tissue disease in our population. It is characterized by different manifestations which if left undiagnosed and untreated lead to serious complications. The hallmark of this disease is fibrosis of various organs including skin and also involving pulmonary, gastrointestinal and cardiovascular system. We aim to evaluate the clinical and serological characteristics of SS in our population. In addition, we evaluated the prevalence of Fibromyalgia and Depression in patients with SS.Objectives:We aimed to determine Clinical and Serological Characteristics of Systemic Sclerosis visiting our department of Rheumatology, Fatima Memorial hospital, Lahore.Methods:It is a cross-sectional study of 38 patients visiting outdoor and indoor in Rheumatology department of Fatima Memorial Hospital from September 2019 to January 2020. All systemic sclerosis patients with age 16 years or above were included in this study. After taking informed consent, we filled the performas to record all the required information. We evaluated the clinical, serological and radiological features of Systemic Sclerosis.Results:A total of 38 patients were included in the study with mean age was 34.47 ± 1.53 years. Female gender comprised of 32(84.2%), with male to female ratio of 1:5.3. Thirty-four (89.5%) had developed Raynaud phenomenon and sclerodactyly was found in 34(89.5%), digital ulcers in 25 (65.8%), and tendon friction rub in 12 (31.6%) patients. Skin tightness proximal to elbow was present in 9 (23.7%). Microstomia (decreased mouth opening) was present in 32(84.2%) patients. Twenty-eight (73.7%) patients had arthritis.Respiratory symptoms comprised of shortness of breath in 36(94.7%), palpitation in 24 (63.2%) and chest pain in 7(18.4%). Gastrointestinal (GI) symptoms comprised of regurgitation in 31 (81.5%) and dysphagia in 14 (36.8%). Interstitial lung disease was present in 30 (78.9%) patients, with higher prevalence in diffuse scleroderma (100%) than in limited scleroderma (70%) (p=0.01). Pulmonary hypertension was present in 18 patients, with significantly higher prevalence in diffuse disease (57.1%), that was secondary to interstitial lung disease and in limited disease it was found in (11.8%) (p<0.01). Thirty (78.9%) patients were found to have restricted disease on pulmonary function tests.Obstetric history showed a higher prevalence of primary infertility in at least 6 (15.8%) patients, with significantly higher prevalence in limited systemic sclerosis disease as compared to diffuse disease (23.5% vs 9.5%, and p=0.05). Fibromyalgia diagnosed as per ACR criteria was present in 7 (18.4%) patients, and depression assessed by Hospital Anxiety and depression (HADS) score was present in 10 (26.3%) patients.Anti nucleic acid antibody (ANA) was found positive in 30 (78.9%) patients. Anti Scl-70 antibodies were in 24 (63.2%) patients, with significant association with diffuse disease (85% vs 35.3% and p<0.01), while anti centromere antibodies were present in 20 (52.6%) patients; significantly higher in limited disease (94.2% vs 19.0%, and p<0.01).Conclusion:Scleroderma is a very important, autoimmune multisystem disease. It has female preponderence. Raynaud phenomenon is the most initial clinical feature followed by other manifestations of variable course and disease severity. Interstitial lung disease and pulmonary hypertension were the most important complication found in our patients which has poor prognosis. So, It is imperative to early diagnose and treat the disease manifesations to prevent future complications.Keywords:Scleroderma, Systemic sclerosis.Disclosure of interest:Sadia Asif: None declared, Muhammad Haroon: None declared, Dr Asadullah Khan: None declared, Dr. Muhammad Faiq: None declareDOI: 10.1136/annrheumdis-2021-eular.1635

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Systemic sclerosis

Practical management of the pregnant patient with rheumatic disease ◽

10.1093/med/9780198845096.003.0017 ◽

2021 ◽

pp. 179-184

Author(s):

Eliza Chakravarty

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Fibrosis ◽

Pregnancy Outcomes ◽

Disease Onset ◽

Scleroderma Renal Crisis ◽

Cutaneous Manifestations ◽

Organ Manifestations ◽

Pulmonary Arterial ◽

Relative Prevalence ◽

Renal Crisis

Systemic sclerosis (SSc) is characterized by a non-inflammatory vasculopathy as well as fibrosis of the skin and vital organs. It presents in two distinct subtypes depending on the extent of cutaneous involvement, with each subtype (diffuse vs limited SSc) having different relative prevalence of extra-cutaneous manifestations. Experience describing pregnancy outcomes in SSc is limited because of disease onset mainly in the 4th and 5th decade. Common symptoms, including cutaneous fibrosis and Raynaud’s phenomenon, are not worsened, and may even improve during pregnancy. Severe organ manifestations of SSc, including pulmonary fibrosis, scleroderma renal crisis, and pulmonary arterial hypertension, are associated with increased risks of pregnancy complications and can be more difficult to treat during pregnancy. Therapies for SSc are mostly directed at managing symptoms with vasodilators, angiotensin-renin antagonists, proton pump inhibitors, and immunosuppressives in the case of pulmonary fibrosis.

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