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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 4 th 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., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

HLA studies in patients with systemic sclerosis (SSc) have shown variable results. This study aimed to examine the association of HLA class I and II risk alleles in Thai SSc patients, and clarify the contribution of risk HLA alleles to the pathogenesis and clinical manifestations. Blood samples from 92 SSc patients and 135 healthy controls (HCs) were collected. Eleven loci of the HLA class I (HLA-A, B, and C) and class II (HLA-DR, DP, and DQ) genes were determined by a 3-field (6-digit) analysis using the Next Generation DNA Sequencing (NGS) method. Anti-topoisomerase-I antibodies (ATA) and anti-centromere antibodies (ACA) were identified by ELISA methods. Allele frequencies (AFs) of HLA-DRB1*15:02:01, DRB5*01:02:01, DQB1*05:01:24, DPB1*13:01:01, and DQA1*01:01:01 were increased significantly in the whole SSc and SSc patients with positive ATA, but with negative ACA (SSc/ATA+/ACA-). Of these, DPB1*13:01:01 was the most susceptible allele. The DRB1*15:02:01, DQB1:05:01:24, and DPB1*13:01:01 alleles were estimated to locate on the unique haplotype, and haplotype frequency was estimated to be significantly higher than those in the HCs (p = 0.002). The linkage analysis of DRB1*15/16 revealed that most of the DRB1*15:02:01 alleles were linked to DRB5*01:02:01 or DRB5*01:08:01N. The linkage of DRB1*16:02:01 to DRB5*01:01:01 was observed frequently. The associations of risk alleles with several SSc clinical features were observed. HLA-DRB1*15:02:01, DRB5*01:02:01, DQB1*05:01:24, and DPB1*13:01:01 on the unique haplotype were associated with the pathogenesis and clinical features of SSc in Thai patients. The linkage of DRB1*15:02:01 to DRB5*01:08:01N was observed commonly in northern Thai patients., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Studies on polymorphisms of the cytotoxic T lymphocytes associated antigen-4 (CTLA-4) genes in rheumatic disease patients are limited in Southeast Asia. This pilot study aimed to determine CTLA-4 polymorphisms in Thai patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and correlate them with serology., Method: One-hundred RA, 70 SLE and 50 SSc patients, and 99 healthy controls (HCs) were included in this study. Polymorphisms of the CTLA-4 gene at +49A/G, -318C/T, -1661A/G and -1722T/C loci were determined by polymerase chain reaction restriction fragment length polymorphism methods. Patient serum samples were determined as follows: RA (rheumatoid factor [RF] and anticyclic citrullinated peptide [anti-CCP]), SLE (antinuclear antibodies [ANA], anti-double-stranded DNA [anti-dsDNA], anti-Smith [anti-Sm], anti-ribonucleoprotein [anti-RNP], and anti-Sjögren's syndrome antigen A [SSA]), and SSc (ANA, anti-RNP, anti-SSA, anti-topoisomerase-1 [anti-Scl70], and anti-centromere antibodies [ACA])., Results: Among the 4 loci studied (+49A/G, -318C/T, -1661A/G and -1722T/C) only the A allele frequency at the +49A/G was significantly higher in the RA patients than their HCs (47.25% vs 35.86%, P = .029, odds ratio [OR] 1.60; 95% CI 1.04-2.47). It also was significantly higher in the subgroup of RA patients with positive RF and anti-CCP than their HCs (47.50% vs 35.86%, P = .020, OR 1.62; 95% CI 1.06-2.47 and 48.89% vs 35.86%, P = .012, OR 1.71; 95% CI 1.11-2.64, respectively). No polymorphisms at these 4 loci were observed in SLE or SSc patients., Conclusion: The A allele at +49A/G locus of the CTLA-4 gene was associated with RA in Thais., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: To determine and compare the prevalence of interstitial lung disease (ILD), the severity of high-resolution computed tomography (HRCT) score and incidence rate (IR) of ILD between the two subsets of early-SSc (systemic sclerosis) patients. We also determined the factors associated with ILD., Methods: We used an inception cohort of early-SSc patients seen between January 2010 and June 2014. All patients underwent HRCT at study entry and annually thereafter., Results: One hundred and thirteen patients (66 females and 89 diffuse cutaneous SSc [dcSSc]) with a mean ± SD age of 53.4 ± 8.4 years and mean disease duration of 12.9 ± 10.3 months at cohort entry were enrolled. At enrollment, patients with dcSSc had a higher prevalence of ILD (78.7% vs. 45.8%, p = 0.002), and a higher total HRCT score (10.3 ± 9.5 vs. 4.4 ± 5.6, p = 0.001) compared with limited cutaneous SSc (lcSSc). DcSSc patients had a higher IR of ILD than lcSSc patients (58.8 vs.17.3 per 100 person-years, p < 0.001). Univariable analysis revealed that male gender, presence of anti-Scl 70 and absent anti-centromere antibody was significant predictors of ILD. In Cox-regression analysis, a positive anti-centromere [hazard ratio (HR) 0.09 95% confidence interval (95% CI 0.01-0.73)] was a protective factor., Conclusions: DcSSc patients had more severe HRCT scores and higher IR of ILD compared with lcSSc patients. Male gender, presence of anti-Scl 70, and absent anti-centromere antibody predicted the future development of ILD in early-SSc patients.

Objective: To compare the high-resolution computed tomographic (HRCT) findings between systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without pulmonary arterial hypertension (PAH), as well as to correlate the calculated HRCT scores and the estimated systolic pulmonary artery pressure (sPAP)., Material and Method: The medical records of all SSc-ILD patients who presented at the Rheumatology Clinic, Chiang Mai University Hospital were retrospectively reviewed Patients with the availability of echocardiography performed within six months of the corresponding HRCT were included The extent of ground glass, lung fibrosis, and honeycombing were scored The maximum diameter of the main pulmonary artery (MPAD) and ascending aortic diameter (AD) were measured The PAH was defined by sPAP >45 mmHg., Results: Fifty patients with SSc-ILD diagnosed with HRCT were included Echocardiography identified 19 (38.0%) patients with PAH. The SSc-ILD with PAH had significantly higher mean (SD) lung fibrosis (9.9 [3.6] vs. 7.8 [3.5], p = 0.03), and CT-total scores (20.5 [6.9] vs. 14.9 [6.2], p<0. 01) than those without PAH. In the total group, the CT-total score correlated positively with sPAP (r = 0.384, p<0.01). No significant correlation of MPAD or MPAD/AD with sPAP was found., Conclusion: SSc-ILD with PAH had more severe lung fibrosis than those without PAH The calculated total HRCT score may be useful to identify PAH in SSc-ILD.

A genetic study, particularly in HLA-DRs, has never been performed in Thai patients with systemic sclerosis (SSc). This study was performed to investigate the association between the HLA-DR series in Thai SSc patients. HLA-DR subtypes were determined in 50 Thai SSc patients and 99 healthy controls (HCs). All SSc patients met the ACR classification criteria for SSc. HLA-DR typing was performed using INNO-LiPA HLA-DRB Decoder kits (INNOGENETICS) and reconfirmed using MICRO SSP HLA DNA Typing kits (ONE LAMBDA). The allele frequency (AF) of HLA-DR*15, compared with HC, was significantly higher in all SSc patients (41.0 vs 21.7%, Pc = 0.0083) and SSc patients with anti-Scl70 antibody positive (anti-Scl70+) (47.1%, Pc = 0.0018). Among the HLA-DR*15 alleles, the AF of the DRB1*15:02 was increased significantly in all SSc patients (29.0 vs 12.6%, Pc = 0.0219) and SSc patients with anti-Scl70+ (32.4 vs 12.6%, Pc = 0.0196). The AF of the HLA-DRB5*01:02 allele was also increased in all SSc patients (27.0 vs 12.6%, Pc = 0.0166) and in SSc patients with anti-Scl70+ (29.4%, Pc = 0.0124). The AF of the DR*04 was significantly lower in the SSc patients (1.0 vs 9.6%, Pc = 0.0399). However, the AF of the DRB1*15:02 and DRB5*01:02 was not different among SSc patients with or without clinical manifestations (pulmonary fibrosis, digital pitting scar, sclerodactyly, myositis, and sicca symptoms). In addition, there was no significant association between clinical manifestations among individuals who carried HLA-DRB1*15:02 or DRB5*01:02. HLA-DRB1*15:02 and DRB5*01:02 alleles were significantly elevated in Thai SSc patients, especially in those with anti-Scl70+. The HLA-DRB1*04 was a protective allele against Thai SSc patients.

This study was performed to determine the prevalence of anti-agalactosyl IgG antibodies in Thai patients with RA, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and determine the sensitivity and specificity of anti-agalactosyl IgG antibodies in the diagnosis of RA in comparison with IgM-rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Serum samples were obtained from 100 patients with RA, 50 cases of SLE, 50 cases of SSc, and 100 healthy controls and analyzed for the presence of anti-agalactosyl IgG antibodies, IgM-RF and anti-CCP antibodies. A serum value greater than mean + 2 standard deviation of normal value of anti-agalactosyl IgG antibodies and anti-CCP antibodies was considered positive. The prevalence of anti-agalactosyl IgG antibodies in RA, SLE, and SSc patients was 88.0%, 14.0%, and 12.0%, respectively. The serum level of anti-agalactosyl IgG antibodies in patients with RA (227.10 +/- 353.64 AU/mL) was significantly higher than those in SLE (11.84 +/- 52.04 AU/mL), SSc (18.85 +/- 99.60 AU/mL), and healthy controls (2.14 +/- 1.97 AU/mL), (p < 0.001). There was a good correlation between the log serum level of anti-agalactosyl IgG antibodies and IgM-RF (r = 0.92, p < 0.001), anti-CCP antibodies and IgM-RF (r = 0.49, p < 0.001), and anti-agalactosyl IgG antibodies and anti-CCP antibodies (r = 0.55, p < 0.001). The sensitivity and specificity in the diagnosis of RA was 88.00% and 96.00% for anti-agalactosyl IgG antibodies, 90.00% and 99.00% for anti-CCP antibodies, and 91.00% and 95.00% for IgM-RF, respectively. The serum level of anti-agalactosyl IgG antibodies was significantly higher in RA than in SLE, SSc, and healthy controls. There was a good correlation between serum levels of anti-agalactosyl IgG antibodies, anti-CCP antibodies, and IgM-RF. These three tests had comparable sensitivity and specificity.

Objective: Study the clinical features of pulmonary arterial hypertension (PAH) in Thai patients with systemic sclerosis (SSc), and compare these features between those with limited (lc) SSc and diffuse (dc) SSc., Material and Method: The medical records of SSc patients attending the Division of Rheumatology, Chiang Mai University were reviewed. PAH was defined by pulmonary arterial systolic pressure (PASP) > 35 mmHg, determined by Doppler echocardiography., Results: Among 275 patients with SSc, 66 had Doppler echocardiography measurement. Thirty-nine patients (59.1%) had PAH. Among the PAH-SSc patients, 36 (92.3%) presented with dyspnea on exertion, and 37 (94.8%) were in a New York Heart Association functional class of II and III. Twenty-four of 39 patients (61.5%) had interstitial lung disease. Diffuse SSc patients had a significantly higher proportion of males, and shorter disease duration between SSc and PAH diagnosis than lcSSc patients., Conclusion: PAH was not uncommon in Thai patients with SSc. Interstitial lung disease might have been the cause associated with over half of these cases. Annual routine Doppler echocardiography screening for PAH in patients with SSc may detect preclinical PAH, and lead to early management and improved functional outcome.

This study was performed to determine the prevalence of ocular and oral sicca symptoms in Thai patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma (Scl). The ocular symptoms and sign (the Schirmer's 1 test) and the oral sicca symptoms and sign (the Saxon's test) in each of 50 RA, SLE and Scl patients were compared with their age-matched controls. The correlation between the presence of sicca symptoms and signs with their clinical activity was also determined. Ocular sicca symptoms were found more common in patients with RA (38% vs 18%, p < 0.05), SLE (36% vs 14%, p < 0.05) and Scl (54% vs 16%, p < 0.01), and oral sicca symptoms were found more common in SLE (22% vs 0%, p < 0.01), and Scl (16% vs 4%, p < 0.05) than their controls. However, only RA patients had a significantly higher proportion of positive Schimer-1 test compared with their controls (p < 0.01). There was no strong correlation between sicca symptoms or signs and other clinical or laboratory variables (age, disease duration, disease activity, disease severity, and antibody to Ro and La antigens) in these three groups. In conclusion, sicca symptoms were seen significantly more common in Thai patients with connective tissue diseases, but the symptoms did not show a good correlation with the clinical and laboratory variables.

Causes of death and poor prognostic factors for patients with systemic sclerosis (SSc) were studied in 222 cases. Their mean age at the onset and duration of disease was 48.9 +/- 12.0 years and 23.3 +/- 29.3 months, respectively. Fifty-three per cent were diffuse subtype. Patients with diffuse SSc had more digital pitting scars and more muscle, heart, lung, and esophageal involvement than those with limited subtypes (p < or = 0.02). One hundred and six patients were lost to follow-up. With a median follow-up duration of 25 months, 31 of the remaining 116 patients (26.7%) died. SSc related death occurred in 18 cases, in which the lung, heart and kidney (renal crisis) were the major causes. Infection contributed to the remaining 13 deaths. When compared with living patients, using a univariate analysis, factors associated with a reduced survival rate were age of > 45 years at the onset, diffuse skin thickness, and lung, gastrointestinal tract, heart, kidney and muscle involvement (p < or = 0.001). In the multivariate analysis, only age of > 45 years at onset and cardiac involvement remained poor prognostic factors (p = 0.04 and 0.001, respectively).