Comparison of clinical features, disease activity, treatment and outcomes between late-onset and early-onset patients with systemic lupus erythematosus. A sex- and year at diagnosis-matched controlled study

Abstract Background Several studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year). Methods The medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups. Results The study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037). Conclusions In this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients.

Paclitaxel-induced diffuse scleroderma with possible scleroderma-renal crisis: a case report and literature review of taxanes-induced scleroderma.

INTRODUCTION/OBJECTIVES: Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer. METHOD: A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis. RESULTS: The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes. CONCLUSION: Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear.

Clinical manifestations, clinical course, and outcomes of immunoglobulin G4-related disease.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an uncommon chronic systemic autoimmune disease, pathologically characterized by lymphoplasma cell and IgG4 plasma cell infiltration with storiform fibrosis. IgG4-RD is a new disease and is not yet widely recognized. The aim of this study was to describe the clinical manifestations and outcomes in Thai patients with IgG4-RD. METHODS: This multicenter retrospective cohort study included patients aged ≥ 18 years who were diagnosed with IgG4-RD, according to the 2011 comprehensive or consensus diagnostic criteria, between 2000 and 2019 in four academic centers in Thailand. Baseline characteristics, laboratory and pathologic findings, treatments, and outcomes were systematically reviewed. RESULTS: The study included 110 patients (71% male) with a mean age (SD) of 59.6 (13.3) years and median disease duration (interquartile range [IQR]) of 28.8 (14.6-53.5) months. Single organ involvement was observed in 60 patients (54.5%). Most patients (96%) had an IgG4 level of more than 135 mg/dL at presentation. Also, most (92%) were treated with corticosteroid (CS) alone or in combination with immunosuppressive agents. The most commonly used immunosuppressive agents were azathioprine (47%) and methotrexate (11%). Additionally, 20% required surgery, and 6.4% underwent stent insertion. One-quarter (26%), 37%, and 29% were in remission with successfully tapering CS, complete and partial response. Nevertheless, 22% relapsed, with a median time to relapse (IQR) of 22.2 (12.8-41.1) months. CONCLUSION: IgG4-RD is a chronic systemic autoimmune disease with diverse manifestations, response to treatment, and outcomes. Most patients responded well to treatments but with a notable relapse rate.

Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction.

Although coenzyme Q10 (CoQ10) supplementation has shown to reduce pain levels in chronic pain, the effects of CoQ10 supplementation on pain, anxiety, brain activity, mitochondrial oxidative stress, antioxidants, and inflammation in pregabalin-treated fibromyalgia (FM) patients have not clearly elucidated. We hypothesised that CoQ10 supplementation reduced pain better than pregabalin alone via reducing brain activity, mitochondrial oxidative stress, inflammation, and increasing antioxidant levels in pregabalin-treated FM patients. A double-blind randomised placebo-controlled trial was conducted. Eleven FM patients were enrolled with 2 weeks wash-out then randomly allocated to 2 treatment groups; pregabalin with CoQ10 or pregabalin with placebo for 40 d. Then, patients in CoQ10 group were switched to placebo, and patients in placebo group were switched to CoQ10 for another 40 d. Pain pressure threshold (PPT), FM questionnaire, anxiety, and pain score were examined. Peripheral blood mononuclear cells (PBMCs) were isolated to investigate mitochondrial oxidative stress and inflammation at day 0, 40, and 80. The level of antioxidants and brain positron emission tomography (PET) scan were also determined at these time points. Pregabalin alone reduced pain and anxiety via decreasing brain activity compared with their baseline. However, it did not affect mitochondrial oxidative stress and inflammation. Supplementation with CoQ10 effectively reduced greater pain, anxiety and brain activity, mitochondrial oxidative stress, and inflammation. CoQ10 also increased a reduced glutathione levels and superoxide dismutase (SOD) levels in FM patients. These findings provide new evidence that CoQ10 supplementation provides further benefit for relieving pain sensation in pregabalin-treated FM patients, possibly via improving mitochondrial function, reducing inflammation, and decreasing brain activity.

2016 updated Thai Rheumatism Association Recommendations for the use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

AIM: In June 2015, the Thai Rheumatism Association (TRA) approved an update of its recommendation for the use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic (tsDMARD) in the treatment of rheumatoid arthritis (RA) to cover those currently available in Thailand (etanercept, infliximab, golimumab, rituximab, tocilizumab, abatacept and tofacitinib). METHOD: A search of the literature was performed between January 2000 and June 2015. Existing RA recommendations, in relation to the use of bDMARDs and tsDMARD, were identified and evaluated by the AGREE II instrument prior to their use as a 'guide' for developing this TRA recommendation. An additional literature search was performed in order to answer specific clinical questions that could not be found in existing guidelines. RESULT: Thirteen recommendations were developed. They covered the use of RA classification criteria, the aim of RA treatment, when to initiate bDMARDs/tsDMARD or taper or switch them to other medications, as well as monitoring these drugs during their use. In addition, specific issues including their use and vaccination, malignancies, pregnancy and lactation, and perioperative period also were addressed. Public hearings were performed at the annual meeting of the TRA and of the Royal College of Physicians of Thailand. The recommendations were distributed to other professional associations related to RA management, as well as government sectors associated with the reimbursement policy, prior to development of the final version. CONCLUSION: These recommendations will help Thai rheumatologists prescribe bDMARDs and tsDMARD more appropriately when treating RA patients.

Correlation of delta high-resolution computed tomography (HRCT) score with delta clinical variables in early systemic sclerosis (SSc) patients.

BACKGROUND: The correlation of changes (delta: Δ) of high-resolution computed tomography (HRCT) score with the Δ of other clinical variables has not been well studied. The purpose of this study was to determine the correlation of Δ HRCT score with Δ percent predicted forced vital capacity (%pFVC), Δ modified Rodnan Skin Score (mRSS), Δ erythrocyte sedimentation rate (ESR), and Δ percent of oxygen saturation at room air (%SpO2) in patients with early systemic sclerosis (SSc). METHODS: We used an inception cohort of early-SSc patients seen at the Rheumatology Clinic, Chiang Mai University, Thailand, between January 2010 and June 2014. All patients underwent HRCT at study entry and every 12 months thereafter. Thirty-one SSc patients who underwent pulmonary function test (PFT) within 12 weeks of their corresponding HRCT at baseline and last visit were identified. The extent of ground glass (GG), lung fibrosis (Fib), bronchiectasis (B), and honeycombing (HC) was scored, and then aggregated to produce a total (t) HRCT score. RESULTS: Mean ± SD age and disease duration from non-Raynaud's phenomenon (NRP) to undergo HRCT at baseline were 52.2±8.8 years and 11.7±7.1 months, respectively. Seventeen (54.8%) patients were female and 20 (64.5%) were classified as dcSSc. The mean ± SD interval between the two HRCT tests was 16.0±7.2 months. The Δ HRCT scores [total fibrosis scores (t-Fib), total bronchiectasis scores (t-B), and total HRCT score (t-HRCT) scores] and Δ mRSS, but not Δ %pFVC, showed significant change over the observation period. We found significant correlation of Δ total honeycombing scores (t-HC) with Δ ESR (r=-0.44, P<0.05), and Δ t-Fib with Δ %SpO2 (r=-0.38, P<0.05). However, no significant correlation of any Δ HRCT scores with Δ %pFVC and Δ mRSS were observed. CONCLUSIONS: In this study, the changes in the HRCT scores were greater than %pFVC; this, along with their correlations with the changes in ESR and %SpO2, suggest that HRCT scores are a useful and sensitive method for monitoring disease progression in early SSc-related ILD (SSc-ILD).

The Correlation of Muscle Biopsy Scores with the Clinical Variables in Idiopathic Inflammatory Myopathies.

OBJECTIVES: To compare the muscle pathology findings among subgroups of idiopathic inflammatory myopathies (IIM) patients, and to determine the correlations of muscle biopsy scores with muscle power and creatine kinase (CK). METHODS: The medical records of IIM patients consisting of the demographic data, clinical parameters and laboratory conducted were retrospectively reviewed. Their initial muscle biopsies were reviewed, and four domains were scored: inflammation, vascular, muscle, and connective tissue. RESULTS: Ninety-five IIM patients (28 patients with idiopathic polymyositis (PM) 9 idiopathic dermatomyositis (DM), 5 DM associated with malignancy, and 53 PM/DM associated with connective tissue disease) with median (IQR: Q1, Q3) disease duration of 1.2 (0.5, 3.1) months were included. No significant differences in initial muscle pathology findings and muscle pathology score among the subgroups were found. Muscle degeneration and endomysial fibrosis scores were negatively correlated with muscle power (r=-0.23 and-0.24, respectively, p<0.05) and positively correlated with CK (r=0.27 and 0.39, respectively, p<0.01). No significant correlation was detected either inflammation or vasculitis scores with muscle power and CK levels. CONCLUSION: In this study, muscle biopsy cannot be used to differentiate among subgroups of IIM patients. In addition, we found only modest correlation of muscle biopsy scores with muscle power and CK. Further study is necessary to confirm our findings.

Periodontal disease in Thai patients with rheumatoid arthritis.

AIM: To evaluate the prevalence and severity of periodontal disease in patients with rheumatoid arthritis (RA) who attended a rheumatology clinic in a university hospital. METHODS: All consecutive patients with RA who attended the rheumatology clinic between June 2009 and January 2010 were asked to enroll in this study. All participants answered questionnaires, which included demographic data, medical history, medications used and smoking habits. A full mouth periodontal examination, including gingival index, plaque index, probing pocket depth and clinical attachment level was performed. Only cases that had at least 20 teeth were included in this study. Rheumatoid arthritis parameters, including number of tender and swollen joints, erythrocyte sedimentation rate, the presence of rheumatoid factor (RF), hand radiographs, Disease Activity Index (DAS) and health status using the Thai Health Assessment Questionnaire (HAQ), were determined. The association between RA parameters and periodontal condition was examined. RESULTS: There were 196 participants (87.2% female) with a mean age of 51.7 ± 9.70 years, mean disease duration of 9.62 ± 7.0 years and mean DAS score of 4.64 ± 1.25. Eighty-two per cent were RF-positive. Moderate and severe periodontitis were found in 42% and 57%, respectively. Higher age, male gender, previous or current smoking and high level of plaque score were associated with severe periodontal disease. No differences in RA parameters were found between groups of patients who had moderate and severe periodontitis. CONCLUSIONS: We found a high prevalence of periodontitis in Thai patients with RA. However, there was no association between RA parameters and periodontal conditions.

Comparison of proteinuria determination by urine dipstick, spot urine protein creatinine index, and urine protein 24 hours in lupus patients.

BACKGROUND: A simple, convenient, and accurate method for detecting urine protein excretion in lupus nephritis is crucial. OBJECTIVES: The objectives of the study were to determine the sensitivity and the specificity of the qualitative urine dipstick test value to detect 0.50 g or greater of the quantitative 24-hour urine protein (24-hUP) in lupus patients, to evaluate an overall agreement of the dipstick test results and the magnitude of 24-hUP, and to examine the correlation between the spot urine protein creatinine index (S-UPCI) and the 24-hour UPCI with that of the 24-hUP. METHODS: A prospective study was conducted in 92 patients with lupus. All dipstick test values from 5 dipstick assays (Bayer, Roche, Meditest USA, Standard Diagnostics, and Arkray) and the S-UPCI were obtained within 6 hours of the 24-hUP collection. Of 149 urine samples, only 39% were collected properly and were used for analysis. RESULTS: The sensitivity and specificity of a ≥ 2+ dipstick test result to detect 0.50 g or greater 24-hUP were 56-% to 80% and 67% to 92%, respectively. The agreement of the urine dipstick test values and the magnitude of 24-hUP was fair (κ = 0.23-0.32). The correlation between the S-UPCI and the 24-hUP was 0.83 (P < 0.0001), and that of the 24-hour UPCI and the 24-hUP was 1 (P < 0.0001). Using 24-hUP 2 g/d or less, the bias ± 1.96 SD of the difference of S-UPCI and 24-hUP was 0.23 (SD, 0.96) g. CONCLUSIONS: A ≥ 2+ dipstick test is relatively sensitive to detect significant proteinuria, but it is poorly correlated with quantitative 24-hUP. The S-UPCI and the 24-hUP can be used interchangeably for follow-up in lupus nephritis patients with proteinuria of less than 2 g/d.

Validation of the Thai version of a screening questionnaire for detection of systemic lupus erythematosus.

OBJECTIVE: The present study was performed to assess the sensitivity and specificity of the translation questionnaire for Systemic Lupus Erythematosus (SLE) in Thai speaking populations. MATERIAL AND METHOD: The 10- item questionnaire was applied to out-patients at the rheumatology clinic of the Chiang Mai University Hospital. One hundred and thirty-nine SLE, 109 Rheumatoid Arthritis (RA), and 35 Scleroderma (Scl) patients, as well as 88 Healthy Controls (HC) were enrolled into the present study. RESULTS: All subjects completed the questionnaire within 2 minutes. A positive response to three or more questions of the questionnaire gave a sensitivity and specificity of 92.81% and 76. 39%, respectively, and was comparable to the original version. CONCLUSION: This Thai-version of the screening questionnaire should be applied in the general population to determine the prevalence of SLE.

Human pythiosis, a rare cause of arteritis: case report and literature review.

OBJECTIVE: To present a case of Pythium insidiosum arteritis and review reported cases of human pythiosis. METHODS: Search of MEDLINE (PubMed) and the Thai Index Medicus was performed using the words "pythiosis" and "pythium." Search of abstracts from a scientific meeting also was performed. Only reported cases in the English or Thai language, with enough clinical information for analysis, were included. RESULTS: There were a total of 32 cases of human pythiosis, with 31 identified in the literature. Twenty-five cases were Thai. Twenty of 21 patients with known occupations were farmers. There was ocular infection in 9 cases, subcutaneous infection in 5 cases, arterial infection in 17 cases, and cardiopulmonary infection in 1 case. Thalassemia was a common associated finding. In addition to systemic antifungal therapy, surgery was required in most cases. The highest mortality rate was seen in the arteritic form, particularly in patients with arterial lesions proximal to the superficial femoral artery. CONCLUSIONS: Human pythiosis is rare. Physicians should be suspicious of pythiosis in individuals, particularly farmers in Thailand, who develop nonhealing cutaneous ulcers or keratitis, which do not respond to conventional treatment. P insidiosum infections should be listed as a rare cause of infectious arteritis.

Kaposi's sarcoma in rheumatic diseases.

OBJECTIVE: To review the clinical features and outcome of all reported cases of Kaposi's sarcoma in patients with rheumatic diseases. METHODS: In addition to our patient, we identified cases from a Medline search between the years 1966 and 2002. Cases associated with human immunodeficiency virus infection were excluded. RESULTS: Including our patient, there were a total of 25 cases reported (11 men and 14 women). Rheumatoid arthritis was present in 8 cases, polymyositis/dermatomyositis in 5, vasculitis syndromes in 5, systemic lupus erythematosus in 3, polymyalgia rheumatica in 2, and 1 each of undifferentiated connective tissue disease and Behcet disease. All but 1 patient had been given systemic corticosteroids for a duration that ranged from 6 weeks to 22 years, and immunosuppressive drugs from 25 days to 3.5 years. The Kaposi's lesions usually involved the skin on the extremities; internal organ involvement occurred in 7 cases. Most lesions responded to a decreasing dosage of corticosteroids and immunosuppressive drugs, or to the administration of radiation or cytotoxic therapy. Six patients died, 4 of which were related to the progression of Kaposi's sarcoma. CONCLUSION: Kaposi's sarcoma in patients with rheumatologic conditions is rare. The clinical features are similar to those with classical Kaposi's sarcoma. Tumor regression usually occurs with decreasing corticosteroids and/or immunosuppressive drugs, local irradiation, or cytotoxic therapy.