Diffuse Cutaneous Systemic Sclerosis Subset Research Articles

Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients

Anti-topoisomerase-I antibody (ATA) is associated with disease severity and internal organ involvement in patients with systemic sclerosis (SSc). The correlation between ATA levels and the clinical course of SSc is unclear. We aimed to determine the correlation between ATA level and survival time and the onset of internal organ fibrosis in SSc patients. This historical cohort study was conducted in adult SSc patients with quantitative tests of ATA between January 2019 and December 2022. Patients with overlap syndrome and no quantitative ATA test were excluded. According to the sample size calculation, and 10% compensated for missing data, a total of 153 patients were needed. The respective mean age on the study date and median ATA level was 59.9 ± 11.3 years and 370 U/mL (range 195–652). Most cases (107 cases; 69.9%) were the diffuse cutaneous SSc subset. According to a multivariable analysis, the ATA titer had a negative correlation with the onset of cardiac involvement (Rho − 0.47, p = 0.01), and had a positive correlation with skin thickness progression (Rho 0.39, p = 0.04). Eleven cases exhibited ATA levels < 7 U/mL and outlier ATA levels were excluded, 142 cases were included in the sensitivity analysis, and multivariable analysis showed the correlation between early onset of ILD and cardiac involvement (Rho − 0.43, p = 0.03 and Rho − 0.51, p = 0.01, respectively). The ATA level was correlated with neither the survival time nor the onset of renal crisis in both analyses. High ATA levels were correlated with a short onset of ILD and cardiac involvement and the presence of extensive skin tightness. Quantitative tests of ATA could serve as an effective tool for identifying patients at risk of an unfavorable prognosis.

P135 Association of Serum Anti-Muscarinic 3 Antibodies with Gastrointestinal Disease in Systemic Sclerosis

Abstract Background/Aims Gastrointestinal (GI) complications of systemic sclerosis (SSc) are frequent and debilitating with symptoms ranging from reflux to faecal soilage. The pathogenesis of GI disease in SSc is poorly understood. Circulating antibodies against Muscarinic type 3 Receptors (anti-M3R) have been implicated in GI smooth muscle dysfunction and neural activation impairment. We examine whether anti-M3R antibodies associate with objective measures of gastrointestinal symptoms. Methods Sera were collected from SSc patients fulfilling the American College of Rheumatology (ACR) classification criteria for SSc. Healthy control (HC) sera were obtained from age-matched volunteers. SSc patients completed the UCLA GIT 2.0 (UCLA GIT) questionnaire. Serum anti-M3R antibodies were measured using specific enzyme-linked immunosorbent assay (ELISA)(CellTrend GmbH, Germany). SSc sera had elevated anti-M3R antibodies if the concentration exceeded two standard deviations above the mean of HC sera. Statistical comparisons were made using Fisher’s exact test and two sample t-test. Results Sera from 40 SSc patients and five HC were assayed for anti-M3R antibodies. Anti-M3R antibody was higher in SSc patients in comparison to HC (1547 vs 1183U/ml, p = 0.33). Anti-M3R antibody levels were significantly elevated in nine (23%) SSc patients. Cohort characteristics were compared based on anti-M3R antibody levels for SSc patients (Table 1). Group demographics were similar in gender, age and disease duration. There was a trend for higher anti-M3R antibodies in limited compared with diffuse cutaneous SSc subset (66.7 vs 32.2, p = 0.12). Although there was no significant association between Anti-M3R antibody level and GIT score (r = 0.014 p = 0.51), SSc patients with elevated anti-M3R antibody did report numerically more severe reflux symptoms (1.24 vs 0.8, p = 0.23) and fewer lower GI domains of severe soilage (0.56 vs 0.87, p = 0.37) and constipation (0.28 vs 0.52, p = 0.2). Conclusion These results show that there is a subset of SSc patients with elevated anti-M3R antibodies which could be pathogenic by perturbing cholinergic neurotransmission in the GI tract. The trend observed of elevated anti-M3R antibodies with more severe GI symptoms warrants further exploration in a larger cohort of SSc. If confirmed, our findings provide mechanistic rationale for reported benefit from intravenous immunoglobulin on symptom severity in SSc GI disease. Disclosure E. Roblin: None. C. Beesley: None. R. Maclean: None. F. Ahmed: None. C. Murray: None. V.H. Ong: None. C. Denton: Consultancies; C.P.D. has received consulting fees from Arxx Therapeutics, Roche, Janssen, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Boehringer Ingelheim, CSL Behring and Acceleron. Honoraria; C.P.D. has received honoraria from Janssen, Boehringer Ingelheim, and Corbus. Grants/research support; C.P.D. has received research grants to the institution from Servier, Horizon, Arxx Therapeutics and GlaxoSmithKline.

Prevalence of erectile dysfunction in Thai scleroderma patients and associated factors.

Erectile dysfunction (ED) has been reported among patients with systemic sclerosis (SSc) and primarily limited cutaneous SSc in Caucasians. While there is no data on ED among Thais in whom the diffuse cutaneous SSc subset is common. We aimed to estimate the prevalence of ED among Thais with SSc, evaluate its severity, and determine the associated factors. We did a cross-sectional study among adult Thai male SSc patients. All eligible patients: a) completed the IIEF-15 questionnaire by themselves; b) underwent a genital examination by an experienced urologist to evaluate skin tightness of the penis, scrotum, and phimosis; and, c) were evaluated for Erection Hardness Score. A total of 60 male SSc patients were included. The respective mean age and median disease duration was 54.8±7.2 years and 3.1 years (IQR 1.2-7.2). The definition of ED was fulfilled in 53 cases for a prevalence of 88.3% (95%CI 77.4-95.2), while 65% had severe ED, and none had skin tightness of the genitalia. Eight cases had acquired phimosis, and all were in the ED group. The patients with ED vs. those without ED had significantly lower scores for orgasm, sexual desire, and intercourse satisfaction, and trended to be older, have more severe skin tightness and have higher BMI. ED is a common problem in men with SSc and is mainly categorized as severe. The severity of SSc might increase the risk of developing ED. We found phimosis was a common genital abnormality co-occurring with ED in SSc.

Prevalence and clinical association of sarcopenia among Thai patients with systemic sclerosis

Patients with systemic sclerosis (SSc) have some potential factors associated with an increased risk of sarcopenia. There has been currently no study to examine such associations in SSc patients. We aimed to determine the prevalence of sarcopenia among SSc patients and examine its association with clinical manifestations and laboratory tests. A cross-sectional study was conducted in 180 adult SSc patients at the Scleroderma Clinic, Khon Kaen University, Thailand, between July 2019 and April 2020. Clinical data, laboratory tests for inflammatory markers, serology, hormone, body composition by dual-energy X-ray absorptiometry, handgrip strength, functional lower extremity strength, and usual gait speed were collected and measured. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia. One hundred and eighty patients were recruited. Ninety-four cases (52.2%) were the diffuse cutaneous SSc subset. The respective mean age and duration of disease was 58.8 ± 9.4 and 6.2 ± 5.3 years. Sarcopenia was revealed in 41 SSc patients for a prevalence of 22.8% (95% CI 12.1–34.8), while the prevalence was higher in patients with the diffuse cutaneous SSc (dcSSc) compared to the limited cutaneous SSc. BMI at the onset of SSc and C-reactive protein > 5 mg/dL were significantly associated with sarcopenia with a respective OR of 0.60 (95% CI 0.48–0.75) and 3.18 (1.06–9.54). Sarcopenia is common in patients with SSc, but the prevalence is more pronounced in the dcSSc. Inflammatory markers, particularly the CRP level, are strongly associated. BMI at the onset had a negative association with sarcopenia among SSc patients.

Fingerprint comparison between before disease onset and after systemic sclerosis diagnosis: a monocentric cross-sectional study.

Skin tightness is a hallmark of systemic sclerosis (SSc), and the fingers are an affected body part, so much so that fingerprints can be significantly affected among those with extensive skin tightness of the finger. We aimed to compare the difference between the current and past (pre-disease onset) fingerprints of SSc patients. We conducted a cross-sectional study among adult SSc patients who attended the Scleroderma Clinic, Khon Kaen University, between October 2019, and September 2020. All eligible patients consented to obtaining their current and previous prints from the Central Registration Bureau, Department of Provincial Administration, Ministry of the Interior. The current prints were obtained using the Crossmatch (Lite UE) live scan from the Central Institute of Forensic Science of Thailand. We investigated the concordance between the prints before disease onset and the current (enroll date) via the Printquest AFIS system with officers from the Central Institute of Forensic Science, Thailand. One hundred SSc patients, according to the sample size calculation, were enrolled (mean age 59.4 ± 9.6years; 66% female). Most (70%) had the diffuse cutaneous SSc subset. A respective 59%, 55%, and 6% presented acro-osteolysis, hand deformities, and digital ulcers. Some challenges were experienced in obtaining prints from patients with loss of the fingertip fat pad, finger joint contracture, and/or acro-osteolysis; notwithstanding, all fingerprints were usable and without individualized changes. Fingerprints were affected by fingertip lesions and finger joint contractures; notwithstanding, the prints remained usable for personal identification. Key Points • Skin involvement in systemic sclerosis (SSc) affects the prints, particularly at the fingertip. • Despite disease onset, the fingerprints of SSc patients do not change significantly. • Fingerprints are inadequate for personal identification among SSc patients with hand deformities due to poor quality or difficulty acquiring them.

Skin thickness affects the result of tuberculin skin test in systemic sclerosis

BackgroundSkin thickness is a prominent clinical feature of systemic sclerosis (SSc), but there is no consensus on the cut-off for a positive tuberculin skin test (TST) size and the limitation of the TST for a diagnosis of tuberculosis in SSc. We aimed to identify the cut-off size of an indurated TST and the sensitivity and specificity of the test for the diagnosis of tuberculosis in SSc patients.MethodsA cross-sectional study of 168 adult Thai SSc patients was conducted. The TST was done using 0.1 ml of purified protein derivatives via intradermal injection. The test was interpreted 72 h after testing.ResultsThe median age was 57.2 years. The majority (71.8%) had the diffuse cutaneous SSc subset. All the patients had a BCG vaccination at birth, and 17 (10.1%) had a tuberculosis infection. An indurated skin reaction size of 20 mm had the highest specificity for tuberculosis (99.3%: 95%CI 96.4–100) (ROC 0.53). The skin thickness—assessed using the modified Rodnan skin score (mRSS)—had a significant negative correlation with the reaction size (Rho -0.23; p = 0.003).ConclusionThe TST is not sufficiently sensitive for detecting TB infection in SSc patients, albeit a skin induration of ≥ 15 mm indicates a high specificity for tuberculosis infection. A high mRSS resulted in a smaller skin reaction size when using the TST, which has limited utility as a diagnostic for tuberculosis among SSc patients with severe skin thickness.The manuscript was presented as a poster presentation at the Annual European Congress of Rheumatology EULAR 2019 Madrid 12–15 June 2019. (Ann Rheum Dis. 2019;78(suppl 2): abstract FRI0347) http://dx.doi.org/10.1136/annrheumdis-2019-eular.1456

The prevalence and clinical features associated of hypothyroidism among Thai systemic sclerosis patients

Thyroid disease, particularly hypothyroidism, has been reported in systemic sclerosis (SSc). Some clinical features of SSc can also present in hypothyroidism. Our aims were to determine the prevalence of, and describe clinical features associated with, hypothyroidism in SSc patients. We conducted a historical cohort study of adult SSc patients who underwent screening thyroid function tests at the Scleroderma Clinic, Khon Kaen University, Thailand, between 2009 and 2018. The patients who had any thyroid disorders before the onset of SSc and were diagnosed as an overlap syndrome were excluded. A total of 200 SSc were included according to sample size calculation, among whom the female to male ratio was 2:1. The majority of cases (137; 69.5%) were diffuse cutaneous SSc subset. The mean age was 55.8 ± 10.7 years and the median duration of disease 4.9 (IQR 1.6–9.9) years. Of the total, 9 had primary hypothyroidism (prevalence 4.5%; 95%CI 2.1–8.4) and 22 had subclinical hypothyroidism (prevalence 11%; 95%CI 7.0–16.2). Of the latter 22, 71% had dcSSc. Logistic regression analysis indicated that unexplained anemia was significantly associated with either subclinical hypothyroid or hypothyroidism (OR 2.74; 95% CI 1.17–6.47), whereas Raynaud’s phenomenon had a negative association (OR 0.28; 95% CI 0.11–0.66). Neither severity of skin tightness nor internal organ involvement were associated with hypothyroidism among SSc patients. Clinical-subclinical hypothyroidism is uncommon among SSc patients, it is frequently associated with anemia, and less so Raynaud’s phenomenon. Clinical-subclinical hypothyroidism should thus be considered in cases of unexplained anemia in SSc patients.

Associated factors of early-onset pulmonary hypertension and clinical difference between early- and late-onset pulmonary hypertension in Thai systemic sclerosis

Objectives Pulmonary hypertension (PH) is a major cause of death in systemic sclerosis (SSc). Detection of early-onset PH and its associated factors would be helpful for improving patient care. Our aims were to determine the factors associated with early-onset PH and to define the differences between early- and late-onset PH among SSc patients. Methods A cohort study was conducted of 409 adult SSc patients who had followed-up between January 2014 and December 2016. Early-PH is defined when the onset of PH is diagnosed within 5 years of the disease. Logistic regression analysis was applied to determine the factors associated with early-PH. Results In 3409 person-years, we diagnosed 50 cases with PH confirmation by right heart catheterization, of whom 26 were early-PH (incidence 0.7 per 100 person-years; 95%CI:0.5–1.1). Among SSc with early-PH, 69.2% had the diffuse cutaneous SSc subset and the most common PH classification was PH due to interstitial lung disease (18 cases;69.2%). According to a logistic regression analysis, early-PH was associated with a WHO functional class (WHO-FC) II and higher, cardiomegaly according to chest radiography, and tricuspid regurgitation jet maximum velocity (TRVmax)>2.8 m/s with the respective OR of 20.12 (95%CI:1.59–255.35), 7.42 (95%CI:1.35–40.88), and 8.20 (95%CI:1.17–57.64). To contrast, early-PH had a negative association with gastrointestinal involvement (OR 0.08; 95%CI:0.01–0.56). Conclusions Early-PH is prevalent among SSc patients and the most common cause is interstitial lung disease. A poor WHO-FC, cardiomegaly, and a high TRVmax are associated with early-PH. Gastrointestinal involvement is a protective factor for early-PH in SSc.

Improved survival in systemic sclerosis is associated with better ascertainment of internal organ disease: a retrospective cohort study

Systemic sclerosis (SSc) has high mortality and morbidity. Current management focuses on early detection and treatment of organ-based manifestations. To determine whether the ascertainment of major organ complications of SSc has changed over time and if this is associated with better survival. Retrospective cohort analysis. A total of 520 SSc patients, 234 with disease onset between 1990 and 1993 (historical cohort) and 286 with disease onset between 2000 and 2003 (contemporary cohort), were included. Survival and frequency of internal organ complications were compared between the two cohorts. Five-year survival among diffuse cutaneous SSc (dcSSc) patients has improved from 69% in the 1990-93 cohort to 84% in the 2000-03 cohort (P = 0.018), whereas 5-year survival among the limited cutaneous SSc (lcSSc) patients has remained unchanged-93 and 91%, respectively. Sixteen per cent of the lcSSc subjects and 38% of the dcSSc subjects from the contemporary cohort were diagnosed for the clinically significant pulmonary fibrosis compared with 3 and 7%, respectively, of the historical cohort (P < 0.001). Similarly, the diagnosis of pulmonary arterial hypertension was more frequent in the patients from the contemporary cohort (8 and 7% for lcSSc and dcSSc, respectively) compared with [ < 1% (P = 0.002) and 1% (P = 0.148), respectively] the historical cohort. There was no significant difference between the two cohorts in terms of scleroderma renal crisis and cardiac involvement. Survival has substantially improved for the diffuse cutaneous subset of SSc with better and more complete ascertainment of lung complications as a result of systematic annual screening.

Clinical burden of digital vasculopathy in limited and diffuse cutaneous systemic sclerosis

Background: Vascular damage is a key pathological process in systemic sclerosis (SSc) and accounts for significant disease-related morbidity. To determine the clinical burden of severe digital vasculopathy (SDV), we have...

Oxygen free radical scavenger enzyme polymorphisms in systemic sclerosis

We performed a case–control study of polymorphisms of glutathione S-transferase (GST) isoenzymes and manganese superoxide dismutase (MnSOD) in black South Africans with systemic sclerosis (SSc). The frequency of the GSTM1*B phenotype was significantly decreased in the overall SSc group compared with controls (OR=0.19, p corr<.05), implying a possible protective effect against development of the disease. There was also a trend toward increased MnSODAla allele and phenotype frequencies in the diffuse cutaneous SSc subset compared with controls (OR=2.11 and 3.15, respectively, p corr<.1). Our findings provide new data on the distribution of GST and MnSOD polymorphisms in healthy Africans and further evidence that genetic factors may have a contributory role to play in predisposing to oxidative stress in SSc.