Chingching Foocharoen

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group

IntroductionErectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known.MethodThis study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively.ResultsOf the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynauds symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients.ConclusionsSevere ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

Time-dependent and somatically acquired mitochondrial DNA mutagenesis and respiratory chain dysfunction in a scleroderma model of lung fibrosis

Reactive oxygen species (ROS) have been implemented in the etiology of pulmonary fibrosis (PF) in systemic sclerosis. In the bleomycin model, we evaluated the role of acquired mutations in mitochondrial DNA (mtDNA) and respiratory chain defects as a trigger of ROS formation and fibrogenesis. Adult male Wistar rats received a single intratracheal instillation of bleomycin and their lungs were examined at different time points. Ashcroft scores, collagen and TGFβ1 levels documented a delayed onset of PF by day 14. In contrast, increased malon dialdehyde as a marker of ROS formation was detectable as early as 24 hours after bleomycin instillation and continued to increase. At day 7, lung tissue acquired significant amounts of mtDNA deletions, translating into a significant dysfunction of mtDNA-encoded, but not nucleus-encoded respiratory chain subunits. mtDNA deletions and markers of mtDNA-encoded respiratory chain dysfunction significantly correlated with pulmonary TGFβ1 concentrations and predicted PF in a multivariate model.

Pericardial fluid profiles of pericardial effusion in systemic sclerosis patients.

BACKGROUND Cardiac involvement is one of clinical presentations in systemic sclerosis (SSc). The pericardial fluid profile and the causes of pericardial effusion were our focus. OBJECTIVES To demonstrate the characteristics and causes of pericardial effusion in SSc. METHODS A descriptive retrospective study was performed on SSc patients with symptomatic pericardial effusion at Srinagarind Hospital, Khon Kaen University, Thailand, between January 1, 2000 and December 31, 2010. We excluded pericardial fluid detected by screening echocardiography. RESULTS Thirty medical records of SSc patients with pericardial effusion were reviewed. The respective mean age and median duration of disease at the time of effusion detection was 52.2±10.8 years and 11.4 months (IQR 0.03-59.1). The female to male ratio was 3.3:1. The most common signs and symptoms included tachycardia (65%) and right-sided heart failure (30%). One patient was diagnosed with cardiac tamponade due to tuberculous pericarditis. Pericardiocentesis and fluid analysis were performed in 9 patients, all of whom had pericardial fluid lactate dehydrogenase (LDH) <200 U/L and a fluid-serum LDH ratio <0.6. Most of the cases (87.5%) had a fluid-serum total protein ratio <0.5. The median white blood cell (WBC) count was 10 cell/mm3 (IQR 6-830), one-third of which was predominated by mononuclear cells. The pericardial biopsy in 8 patients revealed 4 pericardial fibrosis, 2 non-specific inflammation and 2 granuloma. CONCLUSIONS The pericardial fluid profile for SSc was similar to the exudative profile of pleural fluid. Cardiac tamponade was rare. Most pathological findings of pericardial tissue were associated with fibrosis related to the disease itself.

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.

Prognostic factors of mortality and 2-year survival analysis of systemic sclerosis with pulmonary arterial hypertension in Thailand.

Aims:  Pulmonary arterial hypertension (PAH) is a major complication and cause of death in systemic sclerosis (SSc). Our objective was to identify the predictive factors of mortality and the 2‐year survival rate among Thai sufferers of PAH‐SSc.

Clinical differences between Thai systemic sclerosis patients with positive versus negative anti-topoisomerase I.

Anti‐topoisomerase I antibody (ATA) carries an increased risk of systemic sclerosis (SSc) internal organ involvement. There have been no published comparisons of the clinical characteristics of patients positive and negative for ATA in Thailand, where the positive rate for ATA is higher than among Caucasians.

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.

Characteristics, treatments and outcome of psychosis in Thai SLE patients

OBJECTIVES To study the clinical characteristics and outcomes of psychosis and its clinical correlation with disease activity in Thai systemic lupus erythematosus (SLE) patients. METHODS From 750 SLE patients, 36 episodes of psychosis or psychotic depression in SLE patients were retrospectively identified between June 1999 and June 2009 at Srinagarind Hospital, Khon Kaen University. The clinical characteristics, laboratory analyses, disease activity, treatments and outcomes were studied. RESULTS A total of 35 SLE patients had 36 psychotic episodes that consisted of 29 psychotic episodes and 7 psychotic depressive episodes. Eleven episodes (30.6%) occurred during the first manifestation of lupus. Psychotic symptoms included persecutory delusion (50%), bizarre delusion (44.4%), third person auditory hallucinations (44.4%) and visual hallucinations (36.1%). Twenty four episodes (67%) were associated with active lupus in CNS and other organs. All patients received immunotherapy and psychotropic treatments. Psychosis and depressive psychosis were treated with antipsychotics and antidepressants for a mean duration of 71 and 410 days. One death resulted from suicide, and one of thirty four cases (2.9%) had a reoccurrence within a mean follow-up period of 44 months. CONCLUSION About one-third of the psychotic episodes occurred during the first manifestation of lupus. Persecutory delusion, bizarre delusion, third person auditory hallucination, and visual hallucination were common. During psychotic episodes, lupus activity was active in other parts of CNS and organs in 67% of patients. Depressive psychosis required psychotropic treatment longer than psychosis alone. The psychiatric outcome was very favorable. Most of psychotic episodes (97.1%) were fully remitted and rarely showing recurrences.

Incidence rate and causes of infection in Thai systemic sclerosis patients.

Infection is a common cause of death in systemic sclerosis (SSc) but despite immunosuppressant therapy, there are few reports of opportunistic infection.

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).