Systemic lupus erythematosus may have an early effect on peripheral nerve function in patients without clinical or electrophysiological neuropathy: comparison with age- and gender-matched controls.

Asymptomatic electrophysiological peripheral neuropathy is described in systemic lupus erythematosus (SLE) patients. To determine if SLE could have an even earlier effect on peripheral nerve function even before the development of electrophysiological abnormalities, we compared nerve conduction studies (NCS) of SLE patients without electrophysiological or clinical peripheral neuropathy with healthy controls. Consecutive SLE patients without clinical neuropathy (or other known causes of neuropathy) underwent sensory and motor NCS of all four limbs. Results of 61 patients without electrophysiological criteria of neuropathy were compared with age- and gender-matched controls. Although still within the laboratory's range of normal values, significant differences were found in several NCS parameters between patients and controls. SLE patients had lower amplitudes for ulnar, fibular, and tibial compound muscle action potentials (CMAP) and sural sensory nerve action potentials (SNAP); slower conduction velocities for median, ulnar, and fibular motor nerves, and median, ulnar and sural sensory nerves. SLE patients also had longer minimum F-wave latencies for median, ulnar, fibular, and tibial nerves. H reflexes were more often absent in patients. Correlations were found between the number of disease relapses and motor conduction velocities of the fibular and tibial nerves. SLE may have early effect on peripheral nerve function in patients even before they develop electrophysiological or clinical neuropathy.

Early damage as measured by SLICC/ACR damage index is a predictor of hospitalization in systemic lupus erythematosus (SLE).

BACKGROUND: Hospital admissions and re-admissions in lupus patients are common occurrences that can lead to poor prognosis. OBJECTIVES: We evaluated the leading causes of all-cause hospitalizations and their predictive factors in the Malaysian multi-ethnic SLE patients. METHODS: This is a retrospective study involving 300 SLE patients. Demographic data and details of hospitalizations from the year 1988 until 2019 were reviewed. Baseline and latest disease activity (SLEDAI-2 K) and SLICC/ACR damage index (SDI) scores were evaluated. To be eligible for this study, their SLE diagnosis and disease duration was at least one year; this is to ensure that the baseline disease damages were measured at least after 6 months of diagnosis and subsequent disease damage indexes were captured. RESULTS: Majority were of Chinese ethnicity 150 (50%). The cohort's median age was 48 (18-82) years and median disease duration was 13 (1-52) years. 133 (44.3%) had SDI score of ≥1 at baseline (early damage). 69 (23%) had developed new organ damage during this study period.There were 222 (74%) patients ever hospitalized from this cohort. The main cause of hospitalization was lupus flare which included concurrent infection (n = 415 admissions, 46%), followed by elective admissions for procedures and others (n = 284 admissions, 31.5%). Admissions for treatment and disease related complications were 13.8%. 8.7% of admissions were due to infections alone. Median length of stay for SLE-related cause admissions was longer compared to non-SLE related causes. Jointly predictive factors for hospitalization were anti-phospholipid syndrome (OR 5.82), anti-Smith (OR 6.30), anti-SSA (OR 3.37), serositis (OR 14.56), neurological (OR 5.52) and high baseline SDI (OR 1.74), all p < 0.05. CONCLUSION: Early damage in lupus as measured by SDI is a predictive value of hospitalization. Optimization in managing patients with pre-existing damage is crucial to reduce hospitalization risk and subsequent complications.

Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis.

OBJECTIVE: IVIG is known to confer significant benefit in rheumatologic conditions, including inflammatory myopathy. This study aimed to assess the efficacy of IVIG across different aspects of internal organ involvement in refractory active SSc, particularly the gastrointestinal (GI) system. METHODS: SSc patients with overlap polymyositis who remained active and unresponsive to conventional disease-modifying agents and who subsequently received IVIG were identified. GI symptoms were assessed using validated questionnaires. The Medical Research Council Sum Score for muscle strength and modified Rodnan skin score (mRSS) were assessed. Serial measurements were undertaken at baseline prior to the first IVIG treatment and post-treatment in the most recent assessment. RESULTS: Fifteen SSc patients were consecutively recruited into this observational study. The mean duration of IVIG treatment was 2.3 years, with treatment frequency ranging from every 6 weeks to 4 months. Compared with baseline, there was a significant reduction in gastro-oesophageal reflux frequency and intensity mean scores (P = 0.006 and P = 0.013, respectively). Significant improvement in the Gastrointestinal Tract (GIT) 2.0 score from a baseline mean score of 1.07 (s.d. 0.67) to 0.60 (0.46) (P = 0.002) was observed. There was regression in the markers of muscle disease with a reduction in the mean (s.d.) Medical Research Council sum score and the median creatine kinase level (P = 0.001 and P = 0.025, respectively). Significant amelioration of the mean basal modified Rodnan skin score from 21.5 (s.d. 13.8) to 10 (10.6) (P = 0.005) was observed. CONCLUSION: IVIG may be a helpful adjunctive therapy in the amelioration of some key clinical aspects in refractory SSc. Sustained benefit from IVIG suggests a specific immunomodulatory effect on those with established SSc GI complications.

High-resolution oesophageal manometry and 24-hour impedance-pH study in systemic sclerosis patients: association with clinical features, symptoms and severity.

OBJECTIVES: To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients. METHODS: This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed. Their associations with serological features and other organ involvement were evaluated. RESULTS: Twenty-five (80.6%) patients had gastroesophageal reflux disease (GORD) symptoms, mainly heartburn (45.1%), regurgitation (32.2%) and dysphagia (29%). Using manometry, oesophageal dysmotility was detected in 24 (88.9%) patients, while hypotensive lower oesophageal sphincter (LOS) was observed in 17 (63%) patients. 21 (84%) patients had GORD based on pH study. Hypotensive LOS was significantly associated with presence of digital ulcers. The main gastroesophageal symptoms were absent in majority of the SSc patients including in those with severe gastroesophageal manifestations demonstrating failed peristalsis >75%, hypotensive LOS, Demeester score >200 and acid reflux >200 per day. Demeester score >200 is associated with severity of GORD symptoms. Demeester score >200 was also associated with restrictive lung pattern (p=0.001). Significant association between GORD severity (daily number of acid reflux episodes >200) and pulmonary fibrosis was seen (p=0.030). CONCLUSIONS: The presence and severity of gastroesophageal symptoms may not accurately reflect the seriousness of oesophageal involvement. GORD severity is associated with presence of restrictive lung pattern and pulmonary fibrosis. Oesophageal manometry and 24-hour pH study should be considered more frequently in the assessment of SSc patients.

Helicobacter pylori in gastrointestinal manifestation of systemic sclerosis.

Aim: To study the prevalence of Helicobacter pylori in systemic sclerosis patients and its gastrointestinal manifestations in comparison with Helicobacter pylori-negative systemic sclerosis patients. Systemic sclerosis gastrointestinal outcome post Helicobacter pylori eradication was evaluated. Method: In total, 70 systemic sclerosis patients and 70 age-, gender- and race-matched healthy controls had their urea breath test done. Gastrointestinal manifestations in systemic sclerosis were assessed using University of California at Los Angeles 2.0 and Leeds Dyspepsia Questionnaire questionnaires. Systemic sclerosis patients with confirmed Helicobacter pylori infection were given standard Helicobacter pylori eradication therapy. Urea breath test was repeated 6 weeks posteradication therapy with their gastrointestinal symptoms reassessed. Results: The prevalence of Helicobacter pylori was low in both systemic sclerosis patients (10%) and healthy controls (2.9%). There was no significant difference in gastrointestinal symptoms between Helicobacter pylori-positive and Helicobacter pylori-negative systemic sclerosis patients. However, the Helicobacter pylori-positive patients reported higher median severity scores for the gastrointestinal symptoms of reflux (0.5 vs 0.35), abdominal distension (1.5 vs 0.75) and social functioning impairment score (0.5 vs 0.16) using the University of California at Los Angeles 2.0 score. The Helicobacter pylori-positive patients also indicated increased upper abdominal pain (3.0 vs 0.0), regurgitation (2.0 vs 0.0) and burping (3.0 vs 0.0), observed from the Leeds Dyspepsia Questionnaire scores. Gastrointestinal outcomes post-Helicobacter pylori eradication showed either an improvement or complete resolution of symptoms. Conclusion: Gastrointestinal symptoms in systemic sclerosis patients are unlikely to be caused by Helicobacter pylori in the recent years in our cohort of patients. No significant difference in gastrointestinal symptoms was seen between Helicobacter pylori-positive and Helicobacter pylori-negative systemic sclerosis patients. Helicobacter pylori can be readily tested by urea breath test to look for present infection.

Large fiber peripheral neuropathy in systemic sclerosis: A prospective study using clinical and electrophysiological definition.

AIM: The reported prevalence of peripheral neuropathy in systemic sclerosis (SSc) is variable between 0.01% to 28%, probably due to differences in sample size, study design and population. Our aim is to determine the prevalence of large fiber peripheral neuropathy in SSc and to identify any contributing factors. METHOD: A prospective cross-sectional study of 60 SSc patients were evaluated for large fiber neuropathy using the modified clinical Total Neuropathy Score (cTNS) and nerve conduction study (NCS) of the upper and lower limbs. A combination of clinical (cTNS score ≥ 2) and NCS criteria (≥2 abnormal nerves including 1 sural [symmetrical polyneuropathy] and NCS abnormalities consistent with individual nerves/nerve roots [focal neuropathy]) was used to diagnose peripheral neuropathy. RESULTS: The majority had limited cutaneous subset (75%). Mean age was 55.73 (SD ± 13.04) years and mean disease duration was 8.61 (SD ± 8.09) years. Twenty-two (36.7%) had combined clinical and NCS criteria for peripheral neuropathy, 14 (23.3%) with symmetrical polyneuropathy and 8 (13.3%) with focal neuropathy. Symmetrical polyneuropathy patients had significantly lower hemoglobin levels (11.2 vs. 12.35 g/L; P = .047). Serum vitamin B12 levels were normal, therefore excluding vitamin B12 deficiency. No other associations were found for both polyneuropathy and focal neuropathy with demography, co-morbid diseases and SSc disease factors such as Raynaud's phenomenon and modified Rodnan skin score. CONCLUSION: Large fiber neuropathy is common in SSc patients, which could contribute to non-lethal burden in SSc with sensory loss and muscle weakness. Apart from lower hemoglobin in polyneuropathy, there were no associations with disease-specific features or co-morbid diseases.

Fatigue and associated factors in a multi-ethnic cohort of rheumatoid arthritis patients.

INTRODUCTION: Fatigue is an important yet infrequently evaluated component in patients with rheumatoid arthritis (RA) and may have a major impact on quality of life. OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients. METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities). RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P < .02). CONCLUSION: Fatigue was associated with functional disability and has a significant impact on HRQoL in RA. Fatigue assessment should be considered in routine clinical practice for RA patients.

Effects of vitamin D on disease activity and serum interleukin-6 in rheumatoid arthritis.

AIM: Vitamin D3 or 25(OH)D3 may have a potential role in rheumatoid arthritis (RA) pathogenesis by inhibiting the expression of pro-inflammatory cytokines including interleukin-6 (IL-6). The aim of this study is to determine the clinical factors of vitamin D deficiency in multi-ethnic Malaysian RA patients and its association with disease activity, functional disability and serum IL-6 levels. METHOD: One hundred RA patients and 50 healthy controls, sex- and age-matched, were recruited. Disease Activity Score of 28 joints and Health Assessment Questionnaire scores were assessed. Baseline serum 25(OH)D3 and IL-6 were measured in all subjects. RA patients who were vitamin D deficient were given loading doses of vitamin D3 and repeated assessments were done. RESULTS: Vitamin D deficiency (<50 nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient 25(OH)D3 levels compared to Malays and Indians (P < 0.001). Serum 25(OH)D3 level was still negatively associated with body mass index in RA patients (P = 0.002) after adjustment for potential confounding variables. No significant association was seen between 25(OH)D3 levels and disease activity or serum IL-6 levels in both pre- and post-treatment groups. A negative association was observed between serum 25(OH)D3 and functional disability, including a 33% improvement post-treatment (mean ± SD: 0.30 ± 0.46 to 0.20 ± 0.18). CONCLUSION: Vitamin D deficiency is prevalent in Malaysian RA patients. This study suggests that vitamin D is not associated with disease activity or serum IL-6 levels but it may have a role in functional disability in RA patients.

Ethnic differences in the prevalence, socioeconomic and health related risk factors of knee pain and osteoarthritis symptoms in older Malaysians.

Knee pain is often underreported, underestimated and undertreated. This study was conducted to estimate the prevalence, burden and further identify socioeconomic factors influencing ethnic differences in knee pain and symptoms of OA among older adults aged 55 years and over in Greater Kuala Lumpur (the capital city of Malaysia). The sample for the Malaysian Elders Longitudinal Research (MELoR) was selected using stratified random sampling, by age and ethnicity from the electoral rolls of three parliamentary constituencies. Information on knee pain was available in 1226 participants, mean age (SD) 68.96 (1.57) years (409 Malay, 416 Chinese, 401 Indian). The crude and weighted prevalence of knee pain and self-reported knee OA symptoms were 33.3% and 30.8% respectively. There were significant ethnic differences in knee pain (crude prevalence: Malays 44.6%, Chinese 23.5% and Indians 31.9%, p<0.001). The presence of two or more non-communicable diseases (NCD) attenuated the increased risk of knee pain among the ethnic Indians compared to the ethnic Chinese. The prevalence of knee pain remained significantly higher among the ethnic Malays after adjustment for confounders. While the prevalence of knee pain in our older population appears similar to that reported in other published studies in Asia, the higher prevalence among the ethnic Malays has not previously been reported. Further research to determine potential genetic susceptibility to knee pain among the ethnic Malays is recommended.

Vitamin D deficiency is associated with ethnicity and knee pain in a multi-ethnic South-East Asian nation: Results from Malaysian Elders Longitudinal Research (MELoR).

AIM: To determine the association between vitamin D and knee pain among participants of the Malaysian Elders Longitudinal Research (MELoR) study. METHOD: This was a cross-sectional study from the MELoR study consisting of a representative group of 1011 community-dwelling older persons (57% female), mean age 86.5 (54-94) years; 313 were Malays, 367 Chinese and 330 Indians. Participants were asked if they had knee pain. Levels of serum 25-hydroxy cholecalciferol (25-[OH]D), an indicator of vitamin D status, were measured using routine laboratory techniques. RESULTS: In unadjusted analysis, presence of knee pain was significantly associated with vitamin D deficiency (odds ratio [OR] 1.42; 95% confidence interval (CI) 1.08-1.85, P 0.011). Vitamin D levels were significantly associated with ethnicity differences where Malays (OR 7.08; 95% CI 4.94-10.15) and Indians (OR 6.10; 95% CI 4.28-9.71) have lower levels of vitamin D compared to Chinese. Subsequent multivariate analysis revealed that the association between vitamin D deficiency and knee pain was confounded by ethnic differences. CONCLUSION: A previous study suggested that vitamin D deficiency was associated with knee pain. This relationship was reproduced in our study, but we further established that the association was explained by ethnic variations. As vitamin D status is dependent on skin tone, diet and sunlight exposure, which are all effected by ethnicity, future studies are now required to determine whether a true relationship exists between vitamin D and knee pain.

Cytokines in the immunopathology of systemic sclerosis.

Cytokines and growth factors are key regulators of immune activation, vascular alteration and excessive production of extracellular matrix which are hallmark events in the pathogenesis of systemic sclerosis (SSc). They modulate cell-cell and cell-matrix interactions. In particular, cytokines play a central role in the immunopathogenesis of SSc on the basis of molecular pathways which are complex and not completely understood. The majority of cytokines that may be involved in SSc pathogenesis have effect upon or are derived from cells of the immune system, including both the innate and adaptive compartments. Novel therapies that block key mediators that drive the fibrotic response are being developed and appear as potential therapeutic tools in the treatment of SSc, highlighting the importance for an effective therapy targeted towards the molecular and cellular pathways. This article reviews cytokine biology in that context, with particular emphasis on immunopathology of the disease, therapeutic targeting and the way that current or emerging treatments for SSc might impact on cytokine biology.