Management review of scleroderma renal crisis: An update with practical pointers.

Scleroderma renal crisis (SRC) represents severe, fatal internal organ involvement brought on by systemic sclerosis. A high rate of renal replacement therapy and mortality persists despite various treatments. Depending on the stage of SRC, a vasodilator called angiotensin-converting enzyme inhibitor is the treatment of choice. The efficacy of various other vasodilators (i.e. endothelin-1 receptor antagonist) and complement cascade blocker for SRC have been investigated; however, no randomized control trial has been conducted. A new approach has been proposed for the management of SRC, categorized by specific clinical features of narrowly defined SRC and systemic sclerosis-thrombotic microangiopathy. SRC prophylaxis using angiotensin-converting enzyme inhibitor might be harmful, leading to a poor renal outcome, so the pathogenesis of SRC needs to be clarified in order to identify other possible preventions or therapies.

Prevalence of moderate to severe lower urinary tract symptoms in systemic sclerosis.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are common in SSc. The severity of symptoms can affect the quality of life (QOL); however, LUTS is often neglected during routine assessments. We determined the prevalence of moderate to severe LUTS in SSc and its associated factors. METHODS: A cross-sectional study was conducted between March 2020 and June 2020. Adult SSc patients were enrolled from the Scleroderma Clinic, Khon Kaen University, Thailand. All completed a self-administered questionnaire on LUTS using the International Prostate Symptom Score (IPSS), categorized into absent, mild, moderate or severe LUTS. In addition, we investigated the factors associated with moderate to severe LUTS, and the correlation between IPSS-QOL score and IPSS severity. RESULTS: A total of 135 patients were enrolled. Most cases were female (87 cases; 64.4%) and had dcSSc (88 cases; 65.2%). Twenty-six were defined as having moderate to severe LUTS, for a prevalence of 19.3% (95% CI 13.0, 26.9%). In addition, most had storage symptoms (63.0%), followed by voiding symptoms (19.3%) and post-voiding symptoms (12.6%). The factors associated with moderate to severe LUTS per the multivariable logistic regression included a modified Rodnan skin score ≥20 points and gastrointestinal symptoms with adjusted odds ratios 7.64 and 5.78, respectively. In addition, the IPSS-QOL score had a moderate positive correlation with IPSS severity (rho = 0.560, P < 0.001). CONCLUSION: Moderate to severe LUTS occurred in about one-fifth of SSc patients, particularly those with extensive skin tightness and gastrointestinal involvement. The more severe the LUTS, the poorer the QOL.

Factors Associated With Refractoriness to an Up to Fourfold Dosage of Antihistamines in Isolated Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease and has a significant impact on patients' quality of life. The aim of treatment is complete symptom control. AIM: To identify potential factors associated with antihistamine-refractory isolated CSU and to determine the factors that predict response to second-generation H1 antihistamines at dosages from one- to fourfold. METHODS: We conducted a retrospective cohort study, which included adult patients diagnosed with isolated CSU and had complete symptom control. Clinical and laboratory findings were compared between the patients who were responsive to second-generation H1 antihistamines (< fourfold) and those who were refractory to a fourfold dose. Clinical and laboratory data were compared by dosage in the antihistamine-responsive group. RESULTS: There were 182 isolated CSU patients who met the study criteria, of whom 150 (82.4%) were responsive to treatment with up to a fourfold dose of second-generation H1 antihistamines, while 32 (17.6%) were refractory. In univariate analysis, age at onset, body mass index, baseline Urticaria Activity Score-7 (UAS7), white blood cell count, total neutrophil count, neutrophil-lymphocyte ratio, platelet count, and new generation antihistamines were significantly higher in the antihistamine-refractory group. According to multivariate analysis, baseline UAS7 was the only independent factor associated with antihistamine-refractory isolated CSU (odds ratio 1.14, 95% CI 1.01-1.28, P = .03). In the antihistamine-responsive group, white blood cell count tended to predict response to antihistamine treatment (P < .001, 0.04, 0.34 between onefold and twofold, twofold and threefold, and threefold and fourfold, respectively). CONCLUSION: Baseline UAS7 was an independent factor associated with antihistamine-refractory isolated CSU.

Prevalence and clinical association with acro-osteolysis in early systemic sclerosis.

OBJECTIVES: Acro-osteolysis is often associated with systemic sclerosis (SSc). However, the severity of acro-osteolysis and its clinical association among SSc patients is limited. Our aims were to assess the prevalence of acro-osteolysis and the clinical association with acro-osteolysis among SSc patients at early onset of the disease. METHODS: A cross-sectional study of 120 newly diagnosed SSc patients with the onset of less than 4 years were evaluated on clinical characteristics and hand radiographs. Acro-osteolysis was graded on a 0-4-point scale based on the severity and the patients were subdivided into mild, moderate and severe. RESULTS: Among all SSc patients enrolled, 62.5% were females, 56.1% dcSSc and the vast majority of them (84.1%) were positive for anti-topoisomerase I antibody (anti-topo I). The mean disease duration was 2.0±1.3 years. Acro-osteolysis was noted in 77 patients with a prevalence of 64.1% (95%CI 54.9-72.7), of which 16.7% were defined as severe acro-osteolysis. Logistic regression analysis revealed that acro-osteolysis was positively associated with anti-topo I (OR 13.96), hand deformity (OR 3.81) and dysphagia (OR 6.66), but negatively associated with oedematous skin (OR 0.05). Analysis stratified by severity of acro-osteolysis showed significant differences between subgroup in terms of the presence of digital gangrene (p=0.02), ischaemic ulcer (p=0.001), oedematous skin (p=0.001), and hand deformities (p=0.01). CONCLUSIONS: Acro-osteolysis was common in SSc at the early onset of disease. While the presence of anti-topo I, hand deformity and esophageal involvement were strongly associated with acro-osteolysis, oedematous skin was the protective factor for acro-osteolysis.

Prevalence and clinical association with calcinosis cutis in early systemic sclerosis.

OBJECTIVES: Calcinosis cutis is often found with systemic sclerosis (SSc). However the calcinosis cutis and its clinical association among SSc patients is limited. Our aims were to assess the prevalence of calcinosis cutis and its association with clinical features of SSc patients at early onset of the disease. METHODS: A cross-sectional study on clinical characteristics and hand radiographs of 120 newly diagnosed SSc patients with the onset less than four years were evaluated. Calcinosis cutis was described based on the anatomical regions, density (level 1-3) and shapes (net, plate, stone, and amorphous). RESULTS: Among all SSc patients enrolled, 62.5% were females and 56.1% were diffuse cutaneous SSc. The mean disease duration was 2.0 ± 1.3 years. Calcinosis cutis was detected in 60 patients with the prevalence of 50% (95%confidence interval (CI), 0.41-0.59), of which 53.3% occurred at distal phalanx, 96.7% had stone shape and 48.3% were high density. Univariate analysis revealed that calcinosis cutis was associated with age (p = .02) and high-density calcinosis cutis was associated with Raynaud's phenomenon (p = .02), ischemic ulcer (p = .04), and telangiectasis (p = .02). Logistic regression analysis revealed that calcinosis cutis at distal phalanx was negatively associated with edema at the onset (odds ratio, 0.09). CONCLUSION: Occult calcinosis cutis can be detected by hand radiograph in one half of SSc patients at early onset of the disease. Elderly patient has a risk for calcinosis cutis development and Raynaud's phenomenon was associated with high density calcinosis cutis. Calcinosis cutis, particularly at distal phalanx was less likely to be detected in an edematous phase of disease.

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.

Effect of season on clinical outcomes of Thai systemic sclerosis: Analysis of the Thai national healthcare database.

Objectives: We aimed to determine rate of admission, mortality rate, and causes of death in systemic sclerosis (SSc) patients after stratifying by season.Method: A cross-sectional analysis was performed of patients over 15 in the national database with a primary diagnosis of SSc (ICD-10:M34) covered by the National Health Security Office hospitalized between 2014 and 2018. The seasons were stratified into hot, rainy, and Cool dry seasons.Results: Included were 2480 SSc patients with 3684 admissions: most (64.3%) were female. The respective mean age and median length of stay was 56.9 ± 12.3 years and 3 days (IQR 2-6). The admission rate was highest during the rainy season (1574 visits, 42.7%), followed by the cool dry season (1183 visits, 32.1%) then the hot season (927 visits, 25.2%). During the 13,180 person-days, 1660 SSc patients died resulting in a mortality rate of 12.1 per 100 person-days. The proportion of SSc patients who died in the Cool dry season was significantly higher than in the hot or rainy season (p = .04). Pulmonary involvement in SSc was the most common cause of death in the hot season, which is greater than in the other seasons (p = .004). By comparison, death due to cardiac involvement in SSc was common during the rainy season and cool dry seasons (p = .04).Conclusion: The admission rate among Thai SSc patients was greatest during the rainy season, while mortality was highest during the cool dry season. The most common causes of death were SSc-related irrespective of season, particularly cardiopulmonary involvement.

Clinical characteristics and mortality rate of Thai elderly-onset systemic sclerosis.

OBJECTIVES: To identify the clinical differences and mortality rate between adult and elderly onset systemic sclerosis (SSc). METHODS: We conducted a historical cohort study of SSc patients during January 2007-December 2011. The SSc patients were 60 and over classified as elderly onset SSc. Cox regression analysis was used to estimate the probability of survival and for assessing the factors associated with mortality. RESULTS: The medical records of 350 SSc patients were reviewed; 53 (15.1%) had elderly onset SSc. According to the multivariate analysis, elderly onset SSc has a higher WHO functional class, more frequent weakness, more frequent hyperCKaemia, and less pulmonary fibrosis than adult onset SSc (p=0.004, 0.02, 0.02, 0.02, respectively). The incidence of mortality was 3.8 per 100 person-year with a median survival rate of 15.9 years (95%CI 12.4-17.3). The mortality rate of elderly SSc onset was significantly higher than that of adult SSc onset (HR 5.71; 95%CI 3.54-9.20). The median survival of elderly and adult onset SSc was 4.9 years and 16.1 years, respectively. The Cox regression analysis indicated that presence of digital ulcer and tendon friction rub had a respective HR of 7.39 (95%CI 1.28-42.60) and 37.23 (95%CI 2.10-659.09) for predicting mortality of elderly onset SSc. CONCLUSIONS: Myopathy and limitation of physical activity were frequently found among elderly onset SSc over against pulmonary involvement than in adult onset SSc. Mortality of elderly onset SSc was 5.7 times higher, and median survival was 11 years shorter, than adult onset SSc.

Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial.

OBJECTIVES: Twice-daily dosing of proton pump inhibitor (PPI), the standard therapy for gastro-oesophageal reflux disease (GERD), is an effective therapy for GERD in SSc. The aim of this study was to compare the efficacy of omeprazole in combination with domperidone vs in combination with algycon in reducing the severity and frequency of reflux symptoms of PPI partial response (PPI-PR) GERD in SSc. METHODS: Adult SSc patients having PPI-PR GERD were randomly assigned to receive domperidone plus algycon placebo or algycon plus domperidone placebo in a 1:1 ratio plus omeprazole for 4 weeks. The assessment included severity of symptom grading by visual analogue scale, frequency of symptoms by frequency scale for symptoms of GERD and quality of life (QoL) by EuroQol five-dimensions questionnaire scoring. RESULTS: One hundred and forty-eight SSc-GERD patients were enrolled, of whom 88 had PPI-PR. Eighty cases were randomized for either domperidone (n = 38) or algycon (n = 37) therapy. The majority in both groups had the diffuse SSc subset. At the end of the study, no significant difference in symptom grading was found between groups. After treatment and compared with baseline, the severity of symptoms, frequency scale for symptoms of GERD and QoL significantly improved in both groups. Five (13.2%) and 8 (21.6%) respective cases in the domperidone and algycon groups did not respond. CONCLUSION: The prevalence of PPI-PR GERD is common. Domperidone and algycon are equally effective treatments in combination with omeprazole. However, ∼17% of patients were non-responsive, so the effectiveness of domperidone, algycon and PPI combination therapy should be further investigated. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT01878526).

Phototherapy in systemic sclerosis: Review.

Systemic scleroderma-also known as systemic sclerosis (SSc)-is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis-à-vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.

Relationship between Peripheral Arterial Stiffness and Estimated Pulmonary Pressure by Echocardiography in Systemic Sclerosis.

BACKGROUND: Pulmonary hypertension (PH) is an important lethal manifestation of systemic sclerosis (SSc). Evidence of an association between peripheral and pulmonary arterial vasculopathy in SSc has been demonstrated. We hypothesized that peripheral arterial stiffness could predict PH in SSc. METHODS: We performed a cross-sectional study among patients with SSc who underwent Cardio-Ankle Vascular Index (CAVI, VaSera VS-1000; Fukuda Denshi, Tokyo, Japan) and transthoracic echocardiography (TTE) examination to evaluate peripheral arterial stiffness and PH, respectively. The correlation between CAVI score and PH hemodynamics [right ventricular systolic pressure (RVSP) and tricuspid regurgitation velocity (TRV)] was studied. RESULTS: A total of 145 patients underwent both CAVI and TTE evaluation. The mean (standard deviation, SD) patient age was 51.5 (12.3) years; female patients constituted 72% of the subjects. Diffuse SSc occurred in 75% of the cases. The mean (SD) CAVI score was 7.6 (0.9), and the mean (SD) RVSP was 29.9 (11.2) mmHg. Correlation coefficient (r) between CAVI score and RVSP in overall, limited, and diffuse SSc were 0.107 (p = 0.200), 0.040 (p = 0.815), and 0.194 (p = 0.043), respectively. CAVI scores were borderline or abnormal (≥ 8) in 30.3% of subjects. PH was classified intermediate or high probability (TRVmax ≥ 2.9 m/s) in 19.3% of the subjects. Among the overall population, the odds ratios (95% CI) of CAVI score ≥ 8 for TRVmax ≥ 2.9 m/s in univariate and multivariate analysis were 1.23 (0.46-3.21, p = 0.678), and 0.54 (0.10-2.84, p = 0.471), respectively. CONCLUSIONS: Peripheral arterial stiffness, as measured by CAVI, has a correlation trend with the level of pulmonary arterial pressure assessed by TTE, specifically in the diffuse SSc subgroup.

Asymptomatic cardiac involvement in Thai systemic sclerosis: prevalence and clinical correlations with non-cardiac manifestations (preliminary report).

OBJECTIVE: To determine the prevalence of asymptomatic cardiac involvement and its correlation with non-cardiac manifestation in Thai SSc patients. METHODS: A cross-sectional study was carried out between January 2012 and June 2013 at Srinagarind Hospital, Khon Kaen University, Thailand, on adult SSc patients without signs or symptoms suggestive of cardiac involvement. We excluded those with overlap syndrome, having serum creatinine >123.8 µmol/l, history of cardiac diseases, any atherosclerosis risk factors and receiving angiotensin-converting enzyme inhibitors. Non-invasive tests related to cardiac involvement were performed, including: echocardiography, ECG, chest X-ray, inflammatory biomarkers, cardiac enzymes and N-terminal prohormone of brain natriuretic peptide. RESULTS: A total of 103 SSc patients were enrolled, 61.2% of whom were in the subset. Of these, 63 patients had at least one test abnormality (prevalence 61.2%; 95% CI 51.6, 70.7). The two leading cardiac abnormalities were diastolic dysfunction (44.7%) and elevation of cardiac enzymes (36.9%). The only predictor for cardiac involvement per multivariate analysis was the dcSSc subtype with a higher modified Rodnan skin score, and shorter disease duration (odds ratio = 3.37; 95% CI 1.07, 10.65). Compared with the limited subtype, dcSSc was also significantly associated with elevated cardiac enzyme and prolonged distance between a Q wave and T wave in an ECG (QT interval). CONCLUSION: Asymptomatic cardiac involvement in Thai SSc was not uncommon, and the most common finding was diastolic dysfunction. Elevated cardiac enzymes were found in one-third of the patients, which correlated with the dcSSc subtype with a higher modified Rodnan skin score and shorter disease duration, suggestive of early myocardial microcirculation disruption. Long-term follow-up was performed to elucidate the clinical implication of these abnormalities.

Inter- and Intra-Observer Reliability of Modified Rodnan Skin Score Assessment in Thai Systemic Sclerosis Patients: A Validation for Multicenter Scleroderma Cohort Study.

BACKGROUND: Assessment of the severity of skin tightness by the modified Rodnan skin score (mRSS) for systemic sclerosis (SSc) has been found feasible, valid, and reliable. Despite being a major clinical outcome, it has not yet been validated by Scleroderma Research Group. OBJECTIVE: To (a) determine the inter-observer variability vis-à-vis mRSS assessment by members ofthe Scleroderma Research Group before and after mRSS-assessment training by an experienced rheumatologist and (b) determine intra-observer variability. MATERIAL AND METHOD: Between June and August 2013, we conducted a descriptive study of Thai adult SSc patients and all rheumatologists in the Scleroderma Research Group at Srinagarind Hospital, Khon Kaen University, Northeast Thailand. Eleven rheumatologists assessed the mRSS of 22 SSc patients three times (i.e., before and after training, and eight weeks after training). The intra-class correlation coefficient (ICC) and its 95% CI were estimated at week 8 after training. RESULTS: The mean and standard deviation (SD) of mRSS for inter-observer variability analysis was slightly decreased from before training, after training (by an experienced rheumatologist), and at week 8 after training (17.3 ± 11.9, 16.5 ± 11.1, and 16.2 ± 10.3, respectively). Intra-observer variability had moderate agreement before training (ICC 0.59; 95% CI 0.38-0.78), which increased to good agreement after training and at week 8 after training (ICC 0.60; 95% CI 0.42-0.76 vs. 0.68; 95% CI 0.53-0.82, respectively). CONCLUSION: Inter-observer variability for mRSS assessment decreased after training and the reduction persisted for eight weeks after training. The ICC rose from moderate agreement at baseline to good agreement at the end of the study. The mRSS assessment by members of the Scleroderma Research Group was reliable.

Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a EUSTAR group analysis.

OBJECTIVE: The objective of this study was to analyse an association between nailfold capillary abnormalities and the presence and severity of erectile dysfunction (ED) in men with SSc. METHODS: A cross-sectional analysis of the prospective European League Against Rheumatism (EULAR) Scleroderma Trial and Research database was performed. Men with SSc were included if they had undergone nailfold capillaroscopy and simultaneous ED assessment with the 5-item International Index for Erectile Function (IIEF-5). RESULTS: Eighty-six men met the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5 score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED. Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores did not differ between men with early (n = 12), active (n = 27) or late (n = 27) patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no differences in the prevalence of early, active and late capillaroscopy patterns between men with or without ED. CONCLUSION: Neither the presence or absence of abnormal capillaroscopy findings nor the subdivision into early, active and late patterns is associated with coexistent ED in SSc.

Aspiration of the elbow joint for treating radial head fractures.

BACKGROUND: Radial head fracture is the most common fracture of the elbow. It usually results from a fall onto an outstretched arm. In 1954, Mason classified these fractures into type 1 (undisplaced), type 2 (simple displaced), and type 3 (comminuted fractures). Aspiration of the elbow joint aims to relieve pressure in the elbow joint and has been used as an initial treatment option for radial head fractures. However, it is an invasive technique with the potential for complications such as infection and injury to nerves and vessels. OBJECTIVES: To assess the effects (benefits and harms) of elbow joint aspiration for treating radial head fracture in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (14 April 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2014), MEDLINE (1946 to April Week 1 2014) and EMBASE (1980 to 2014 Week 15), trial registries, bibliographies and conference proceedings. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical trials comparing aspiration versus no aspiration for treating radial head fractures in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles, assessed risk of bias and extracted data. Disagreements were resolved by discussion. Where appropriate, we pooled results of comparable studies using fixed-effect meta-analysis. MAIN RESULTS: We included two trials that involved 126 participants but provided results for only 108 participants. Most participants were adults, typically over 30 years of age. Both trials were at high risk of selection, performance, detection and reporting bias. Reflecting this high risk of bias, we downgraded the quality of evidence two levels for study limitations and a further level for imprecision. Thus we judged the evidence for all outcomes to be 'very low' quality, meaning that we are very uncertain about these estimates.One trial included participants with Mason type 1, 2 or 3 radial head fractures and also a few cases of traumatic elbow hemarthrosis without fracture. The other trial included participants with Mason type 1 and 2 fractures. All participants were managed non-surgically.Neither trial reported functional outcome based on validated patient-reported outcome measures of function or pain using validated measures such as a visual analogue scale. Very low quality evidence (108 participants, two trials) indicates little difference between aspiration and no aspiration in impaired function (unable to carry heavy loads; discomfort when carrying loads) at 12 months (9/51 in aspiration group versus 7/57 in the no aspiration group; risk ratio 1.43 favouring no aspiration, 95% confidence interval (CI) 0.57 to 3.58). Very low quality evidence (two trials) suggests a beneficial effect of aspiration on pain relief immediately after aspiration. Very low quality evidence (one trial, 28 participants) shows less pain after aspiration at three weeks, but it is unclear whether this applies subsequently. Neither trial reported on adverse events (for example, nerve and vascular injuries; deep or superficial infection) from the procedure, but aspiration was reported as being unsuccessful in three participants (7.9%) in one trial. Very low quality evidence indicates little difference in range of motion (based on elbow extension) between the two groups at six weeks (28 participants, one trial) or 12 months (108 participants, two trials). The report of adverse events was incomplete, but one trial (80 participants) reported the absence of three specific complications: myositis ossificans, joint instability or late displacement of the fracture. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effectiveness of joint aspiration for the initial treatment of radial head fracture in terms of function, pain and range of motion or to determine the safety of the procedure. An examination of current aspiration use, the prospective collection of adverse events and consultation with patients as to their preferences and values would be helpful in guiding decisions about the future design of a multicentre randomised trial aiming to obtain definitive evidence on the use of aspiration for treating radial head fractures.

Incidence of pulmonary hypertension in patients with systemic sclerosis and no pulmonary symptoms: is annual echocardiographic screening necessary?

BACKGROUND: Annual echocardiographic screening has been recommended for early detection of pulmonary hypertension (PHT) in systemic sclerosis (SSc) patient; however, the cost benefit for cases with no pulmonary symptoms is not well established. OBJECTIVES: The objective of this study was to determine the incidence and clinical predictors of echocardiographic diagnosis of PHT in "asymptomatic" SSc patients. METHODS: A historical cohort of adult SSc patients who underwent echocardiographic screening for PHT at least twice in Khon Kaen University, Thailand, during January 1, 2005, to December 31, 2011, was included. Pulmonary hypertension was defined by an estimate of right ventricular systolic pressure of greater than 40 mm Hg. RESULTS: A total of 143 medical records were reviewed (female-to-male ratio = 1.7:1). The majority had the diffuse subset (94 cases; 69.6%). Seventy-five (52.4%) were without pulmonary symptoms throughout the follow-up period. Of the 403.1 person-years under observation in the asymptomatic group, only 1 had pulmonary arterial hypertension confirmed by right-sided heart catheterization. The incidence of PHT among such SSc patients was 0.2 per 100 person-years (95% confidence interval [CI], 0.006-0.01 per 100 person-years). The disease duration at the time of PHT detection by echocardiography was 5.1 years. The declining functional class (FC) led to the higher incidence of PHT, with incidence of PHT in those who had declining FC I to FC II and FC I to FC III of 2.1 (95% CI, 0.4-6.0) and 4.2 (95% CI, 0.1-23.3), respectively. CONCLUSIONS: The incidence of echocardiography-diagnosed PHT among Thai with SSc, and no pulmonary symptoms was low. Annual echocardiography is less beneficial among such patients; repeated echocardiography should instead be performed on those with a declining FC.

Clinical characteristics and mortality in systemic sclerosis: a comparison between early- and late-referred diseases.

OBJECTIVE: To determine if there is any significant difference in the clinical characteristics and mortality between early-and late-referred systemic sclerosis (SSc). MATERIAL AND METHOD: An historical cohort study was performed among referred-SSc patients at Srinagarind Hospital between January 2006 and December 2010. 'Early referrals'occurred during the edematous phase while 'late referrals' occurred after that. RESULTS: Forty two percent of the SSc cases (229 of 543) were referred; 108 (47.2%) were early-referrals. Early referrals were for proper management (49.1%) and diagnosis (41.7%), whereas the majority of late referrals (79.3%) were for proper management, followed by additional investigations (10.7%). The respective median duration of disease at referral between early and late was 3.7 (IQR 2.6-5.6) and 20.7 months (IQR 12.2-37.4). Joint contracture, cardiac involvement and pulmonary fibrosis presented more frequently among late-referrals (p < 0.001, p = 0.03 and p = 0.04, respectively). The respective mortality rate among early- vs. late-referrals was 15.1 (95% CI 10.0-21.8) vs. 23.0 (95% CI 15.8-32.3) per 100 person-year Two-thirds of deaths were associated with the disease, pulmonary fibrosis being most common among both early- and late-referrals (50 and 42.7%, respectively). CONCLUSION: The number of early vs. late referrals was comparable and cardiopulmonary involvement and joint contracture were common presentations in late-referrals. Late-referral was associated with high mortality commonly from pulmonary fibrosis.

Clinical course and factors associated with progressive acro-osteolysis in early systemic sclerosis: a retrospective cohort study.

To examine clinical course of early systemic sclerosis (SSc) and identify factors for progression of acro-osteolysis by a retrospective cohort study. Dual time-point hand radiography was performed at median interval (range 3.0 ± 0.4 years) in 64 recruited patients. Progressive acro-osteolysis was defined as the worsening of severity of acro-osteolysis according to rating scale (normal, mild, moderate, and severe). Incidence of the progression was determined. Cox regression was analyzed for the predictors. A total of 193.6 per 100 person-years, 19/64 patients had progressive acro-osteolysis with incidence of 9.8 per 100-person-years (95% CI 6.3-15.4). The median time of progressive acro-osteolysis was 3.5 years. Rate of progression increased from 1st to 3rd years follow-up with the progression rate at 1-, 2- and 3-years were 0, 2.0 and 18.3%, respectively. Patients with positive anti-topoisomerase I tended to have more progressive acro-osteolysis but no significant predictors on Cox regression. 44%, 18%, and 33% of who had no, mild, and moderate acro-osteolysis previously developed progression and 10 turned to be severe acro-osteolysis. In conclusion, the incidence of progressive acro-osteolysis was uncommon in early SSc but the rate of progression was pronouncedly increasing after three years follow-up. A half of the patients progressed to severe acro-osteolysis.

Incidence of Systemic Vasculitis and Clinical Outcomes in Systemic Sclerosis: 2-Years Follow-Up of Asymptomatic Positive for Anti-Neutrophilic Cytoplasmic Antibody.

Purpose: Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) overlap with systemic sclerosis (SSc) is uncommon. We aimed to determine the incidence of AAV and define clinical outcomes relevant to asymptomatic screening positive for ANCA in SSc after 2 years of follow-up. Patients and Methods: The study was a cohort study of 185 Thai adult SSc patients testing for ANCA and having a 2-year follow-up at the Scleroderma Clinic, Khon Kaen University, Thailand. The incidence of AAV and outcomes of those who tested positive for ANCA were evaluated. Results: A total of 185 SSc patients were tested for ANCA, of whom 21.6% were positive for either cytoplasmic ANCA, perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), or anti-proteinase3 antibody. Only one 52-year-old female patient with dcSSc, negative for initial ANCA test, developed AAV (microscopic polyangiitis) 7 months after the first ANCA test for an incidence of AAV of 0.27 per 100-person-years (95% CI 0.01-1.5). She was positive for p-ANCA and anti-MPO. Eight of those who had an initial test were positive for ANCA and underwent a repeated test. Only two cases persisted as positive for ANCA (1 anti-MPO and 1 anti-PR3) and had no clinicals suspicious of vasculitis. Four cases that had ANCA turned to a negative result. Conclusion: AAV is a rare complication in SSc, so ANCA may not have any role as a screening test for AAV as it cannot predict the development of AAV in SSc. We suggest testing for ANCA only in SSc patients with clinicals suspicious of AAV.

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.