Positive Anticentromere Antibody Research Articles

Pregnant outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer.

To analyze the pregnant outcomes in patients with positive anti-centromere antibody (ACA) receiving in vitro fertilization (IVF) -embryo transfer (ET) and natural conception. A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received in vitro fertilization-embryo transfer therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnant outcomes were analyzed using self-matching analysis. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure. The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the double pronuclei rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immunosuppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant difference in miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy. Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.

to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients. SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation. One-hundred-fifty-two SSc-patients (mean age 47.3 ± 12.3 years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%) were evaluated over a median(IQR) time of 3.3(1.7-5.0) years. The primary indication for rituximab were interstitial lung disease (ILD)(38.8%), worsening skin fibrosis(36.8%), and arthritis(13.8%); 138 patients(90.8%) received more than one rituximab course. The 5-years rituximab retention rate was 59.9%(44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation[5.7(3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration[sHR 0.8(0.7-0.9)], anti-topoisomerase-I negativity[sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis[sHR 0.3 (0.1-0.8)]. Treatment failure was the second cause of rituximab discontinuation[3.7(2.2-6.0) per 100 patient-year] and was associated with anti-centromere antibody positivity[sHR 2.8(1.1-7.4)] and anti-topoisomerase-I negativity[sHR 0.2(0.1-0.6)]. Adverse events(AEs) were the less common cause of discontinuation[3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset[sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment[sHR 4.5(1.2-16.3)]. rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.

Anti-centromere antibody positivity is an independent variable associated with salivary gland ultrasonography score in Sjögren’s syndrome

Sjögren’s syndrome (SS) is an autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands. SS also exhibits extra-glandular manifestations and specific autoantibodies. Salivary gland ultrasonography (SGUS) is a common procedure used to assess the severity of glandular involvement. However, the association between SGUS and extra-glandular lesions remains poorly understood. This study aimed to identify clinical indices, including disease activity, associated with glandular involvement using SGUS in patients with SS. We included 115 patients with SS and 90 without SS. Patients with SS had significantly higher ultrasonography (US) score than patients without SS. Multivariate analysis revealed focus score, Saxon test positivity, and anti-centromere antibody (ACA) positivity as independent variables associated with the US score in patients with SS. In addition, these results were similar to those obtained in patients with primary SS. Patients with SS and ACA positivity had higher US score and an increased prevalence of hyperechoic bands in the parotid glands and submandibular glands. In conclusion, this study indicated that ACA positivity is associated with the US score in patients with SS. These results suggest that US findings in patients with ACA positivity might show specific changes in the salivary glands, especially fibrosis.

Prevalence of the limited vs. extensive scleroderma-related interstitial lung disease at the time of diagnosis of SSc-ILD based on Goh et al. criteria. Systematic review and meta-analysis

IntroductionGoh et al. proposed in 2008 a classificatory algorithm of limited or extensive SSc-ILD. The prevalence of both at the time of diagnosis of SSc-ILD is not known with exactitude. MethodsThe review was undertaken by means of MEDLINE and SCOPUS from 2008 to 2023 and using the terms: "systemic", "scleroderma" or "interstitial lung disease" [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment for observational studies and the Jadad scale for clinical trials. The inverse variance-weighted method was performed. ResultsTwenty-seven studies were initially included in the systematic review and meta-analysis (SRMA). Of these, 17 studies had no overlapping data. They reported data from 2,149 patients, 1,369 (81.2%) were female. The mean age was 52.4 (SD 6.6) years. 45.2% of the patients had the diffuse subtype and 54.8% had the limited or sine scleroderma subtype. A total of 38.7% of the patients showed positive antitopoisomerase antibodies (ATA) and 14.2% positive anticentromere antibodies (ACA). The mean percentage of forced vital capacity (FVC) at baseline was 80.5% (SD 6.9) and of diffusing capacity of the lungs for carbon monoxide (DLco) was 59.1% (SD 9.6). Twelve studies presented SSc-ILD extension data adjusted for PFTs and were included in the meta-analysis. The 10 observational cohort studies were analyzed separately. The overall percentage of limited extension was estimated at 63.5% (95%CI 55.3–73; p < 0.001) using the random-effects model. Heterogeneity between studies (I2) was 9.8% (95%CI 0–68.2%) with the random-effects model. Extensive pulmonary involvement was estimated at 34.3% (95%CI 26–45.4; p < 0.001). Heterogeneity between studies (I2) was 0% (95%CI 0–61.6%) with the random-effects model. ConclusionThe overall percentage of limited SSc-ILD at the time of diagnosis of SSc-ILD was estimated at 63.5% and extensive at 34.3%.

Digital gangrene in systemic sclerosis patients: not only due to the microvascular disease.

This study aims to investigate the characteristics, risk factors, and outcomes of digital gangrenes in SSc patients, and to identify whether vasculitis is one of the causes for digital gangrene. A retrospective case-control study was performed from February 2003 to April 2021. Forty-three SSc patients with digital gangrene admitted to Peking Union Medical College Hospital were included. One-hundred forty-six age- and sex-matched SSc patients without gangrene were selected as controls during the same period. Univariate and multivariate logistic regression analysis was used to determine risk factors. Among 43 SSc patients with gangrene, 93.0% had Raynaud's phenomenon (RP) and 32.6% had current or previous digital ulcers (DU). SSc patients with digital gangrene had more ESR elevation (54.8% vs. 34.9%, p = 0.020) and higher level of high-sensitive C reactive protein (median 7.2mg/L vs. 1.8mg/L, p = 0.045) compared with controls. In the multivariable logistic regression analysis, smoking history (OR 4.119, p = 0.037), anti-centromere antibody positivity (OR 3.542, p = 0.016), anti-neutrophil cytoplasmic antibody positivity (OR 22.605, p = 0.037), and anti-phospholipid antibody positivity (OR 16.563, p = 0.001), as well as elevated ESR (OR 2.524, p = 0.038) were identified as independent risk factors for gangrenes. Most (79.1%) cases were treated with combination of immunosuppressive and vasodilating therapy, and four cases also got remised after treatment of only glucocorticoid and immunosuppressive agent. Smoking history; positive-ACA, ANCA, and anti-phospholipid antibodies; and increased ESR were independent risk factors for digital gangrenes in SSc. Vasculitis and macrovascular disease may contribute to the progression of digital gangrenes. Key Points •18.6% of SSc patients with digital gangrene had macrovascular stenosis. •Smoking, positive-ACA, ANCA, aPL, and increased ESR were indicators for digital gangrenes in SSc. •Vasculitis and macrovascular disease may involve in the pathogenesis.

Extended autoantibody panel in Turkish patients with early-stage systemic sclerosis: Coexpressions and their influences on clinical phenotypes.

To investigate the frequency and clinical relevance of an extended autoantibody profile in patients with systemic sclerosis(SSc). In this cross-sectional study, serum from 100 consecutive patients was subjected to indirect immunofluorescence (IIF)(HEp-20-10/primate liver mosaic) and Systemic Sclerosis Profile by EUROIMMUNto evaluate anti-nuclear antibodies(ANA) and autoantibodies against 13 different autoantibodies in patients with SSc less than 3 years. Ninety-three of 100 patients were positive for ANA byIIF. Fifty-three patients showed single positivity, 26 anti-topoisomerase antibodies (anti-Scl70 ab), 16 anticentromere antibodies (ACAs), six anti-RNA polymerase III antibodies (anti-RNAPIII ab), one anti-Ku antibody, one anti-PM/Scl100 antibody, two anti-PM/Scl75 antibodies, one anti-Ro52 antibody, whereas 32 patients had multiple autoantibody positivities. Among classic SSc-specific autoantibodies, anti-Scl70 and anti-RNAPIII abs showed the highest cooccurrence (n = 4). One patient was simultaneously positive for anti-RNAPIII ab and ACA, and one was positive for ACA and anti-Scl70 ab. The clinical features were not statistically different between single and multiple autoantibody-positivity for classic SSc-specific autoantibodies (ACA, anti-Scl70 ab, and anti-RNAPIII ab), except for digital ulcer in the multiantibody positive ACA group (p = .019). Based on our results, coexpression of autoantibodies is not uncommon in SSc patients. Although autoantibodies specific to SSc in early disease show generally known clinical features, it remains to be investigated how the coexpression of autoantibodies will affect clinical presentation.

Esclerosis sistémica sine esclerodermia en una mujer con anticuerpos antinucleares centroméricos, afectación pulmonar y digestiva: Reporte de caso

Sine entities are rare in rheumatology. In progressive systemic sclerosis there is a variant of the limited cutaneous form called systemic sclerosis sine scleroderma, whose central feature is the lack of skin involvement, but visceral involvement is present. Positive anti-topoisomerase or anti-centromere antibodies confirm the diagnosis. We present the case of a 63-year-old woman with interstitial lung disease, intestinal transit involvement and Raynaud's phenomenon, with high titers of ANA with a centromeric pattern and positivity for anti-topoisomerase antibodies. When faced with a patient with Raynaud's phenomenon, visceral involvement and elevated ANA, specific antibodies should be requested for the diagnosis of systemic sclerosis in its sine variety.

Laboratory risk factors for coexistent primary biliary cholangitis in patients with Sjögren’s syndrome: a retrospective study

BackgroundLimited research exists on the laboratory characteristics of coexistent primary biliary cholangitis (PBC) and Sjögren’s syndrome (SS). This study aimed to investigate the laboratory risk factors for the coexistence of PBC in patients with SS.MethodsEighty-two patients with coexistent SS and PBC (median age 52.50 years) and 82 age- and sex-matched SS controls were retrospectively enrolled between July 2015 and July 2021. The clinical and laboratory characteristics of the two groups were compared. Laboratory risk factors for the coexistence of PBC in patients with SS were analyzed using logistic regression analysis.ResultsBoth groups had a similar prevalence of hypertension, diabetes, thyroid disease, and interstitial lung disease. Compared with the SS group, patients in the SS + PBC group had higher levels of liver enzymes, immunoglobulins M (IgM), G2, and G3 (P < 0.05). The percentage of patients with an antinuclear antibody (ANA) titre > 1:10000 in the SS + PBC group was 56.1%, higher than that in the SS group (19.5%, P < 0.05). Additionally, cytoplasmic, centromeric, and nuclear membranous patterns of ANA and positive anti-centromere antibody (ACA) were observed more frequently in the SS + PBC group (P < 0.05). Logistic regression analysis showed that elevated IgM levels, high ANA titre, cytoplasmic pattern, and ACA were independent risk factors for PBC coexistence in SS.ConclusionsIn addition to established risk factors, elevated IgM levels, positive ACA, and high ANA titre with cytoplasmic pattern provide clues to clinicians for the early screening and diagnosis of PBC in patients with SS.

E080 Catheter-related venous thrombosis in patients with systemic sclerosis: a case series

Abstract Background/Aims Systemic sclerosis (SSc) is characterised by endothelial dysfunction and vasculopathy, which may lead to venous thrombosis. Here, we report four cases of extensive venous thrombosis of the upper limbs and right atrium associated with implantable venous access devices (port-a-cath) in patients with a diagnosis of SSc, who presented to our specialist centre between 2018 and 2022. Methods We retrospectively reviewed four patients with SSc and port-a-cath-associated thrombosis who presented to the Department of Rheumatology, Royal Free Hospital NHS Trust between 2018 and 2022. All patients are diagnosed with systemic sclerosis according to the 2013 ACR/EULAR classification criteria. Results Three patients were diagnosed with a port-a-cath-associated thrombosis in 2022, and one in 2018. Two patients had limited cutaneous SSc with positive anti-centromere antibodies, and 2 had diffuse subset with anti-U3RNP antibodies. All patients had a right-sided port-a-cath that had been in-situ for at least 3 years. Two patients were diagnosed with right atrium thrombus (measuring 2.2 and 3 cm respectively), one patient with an internal jugular vein and right subclavian thrombosis, and one with a left subclavian thrombosis. None had a history of previous thromboembolic event. A full thrombophilia screen was negative in 2 patients, and is pending in the others. Of note, 2 patients had COVID-19 infection within the 3 months prior the thrombotic event. 1 patient had tocilizumab administered through the line, 1 rituximab and IVIG, the other 2 had prostanoids only. Conclusion We described four recent cases of port-a-cath-associated thrombosis of the upper limbs and right atrium in SSc patients with no previous history of thrombosis. This highlights the increased risk of thrombosis related to long term indwelling catheters in SSc and demonstrates the potential interplay between covid microvasculopathy and the associated thrombotic risks reported with both ACA and antiU3RNP antibodies in SSc. We note that from previous reports the relative lower risk of adverse outcomes in SSc patient receiving parenteral nutrition. Further research into frequency of port-a-cath-related thrombosis in SSc patients is warranted, especially with use of prostanoids, and adequate screening and non-invasive follow up might be needed to avoid life-threatening thromboembolic complications. Disclosure C. Giacomassi: None. T. Eldaw: None. S. Vigneswaran: None. A. Debres: None. C. Denton: None. V. Ong: None.

DOES ADMINISTRATION OF PREDNISOLONE TO ANTI-CENTROMERE ANTIBODY-POSITIVE PATIENTS IMPROVE OOCYTE MATURATION AND FERTILIZATION RATES AFTER OVUM PICKUP AND INTRACYTOPLASMIC SPERM INJECTION?

It has been reported that anti-nuclear antibody (ANA)-positive patients have a lower oocyte maturation rate after ovum pickup (OPU). In particular, patients with positive anti-centromere antibodies (ACA), a member of the ANA family, are more likely to have a lower oocyte maturation rate and abnormal fertilization rate. Previous reports showed that administration of prednisolone in ANA-positive patients improved intracytoplasmic sperm injection (ICSI) outcomes. However, its effects in ACA-positive patients are unknown.

Therapeutic options in refractory anti-MDA5 dermatomyositis triggered by SARS-CoV-2 infection

Anti-MDA-5 dermatomyositis (DM) is a rare disease subtype characterized by rapidly progressive interstitial lung disease alongside skin, vascular and visceral involvement. The severity of the pulmonary disease is corelated with a weaker prognosis. A 31-year-old female patient was admitted for hand arthritis, upper girdle pain and multiple erythematous papular facial lesions on the face, digital ulcerations and Raynaud’s. The symptoms started immediately after the onset of the SARSCoV-2 infection. Positive anti-MDA5 and anti-centromere antibodies were identified, thus amyopathic DM - CREST syndrome overlap diagnosis was placed. Due to pulmonary involvement, corticosteroids, immunomodulatory drugs (mycophenolate mofetil, hydroxychloroquine, cyclophosphamide) were initiated, with no clinical benefits. Lack of response led to initiation of rituximab, oral tacrolimus and nintedanib with no apparent progression of the disease. Refractory cases require escalation of the standard therapeutic approach. SARS-CoV-2 infection can represent a trigger of autoimmunity in DM which needs to be further assessed.

P27 Challenging management of GI complications in Systemic Sclerosis

Introduction/BackgroundSystemic sclerosis is a chronic, progressive, multisystemic autoimmune disease in which there is excessive collagen deposition in the dermis and internal organs. It is commonly categorized into limited cutaneous or diffuse cutaneous systemic sclerosis. In more than 80% of patients there is GI involvement. Gut complications can impair oral intake, absorption and even faecal continence, and consequently can have severe adverse effect on quality of life. With disease progression, management of GI symptoms may become more of a challenge. We present a challenging case of SSs with esophageal involvement along with severe regurgitation who eventually responded to a specific prokinetic.Description/Method70 y/o female initially presented to gastroenterology clinic in 2013 due to dysphagia to solids and was found to have benign fibrotic oesophageal stricture for which she had therapeutic dilatation, (normal biopsy result). Subsequently, she had barium swallow which showed severe regurgitation. Manometry confirmed severely hypo-contractile oesophagus thus she was referred to rheumatology for suspected connective tissue disorder.On initial review, she did not describe typical inflammatory symptoms, scleroderma, sclerodactyly, Raynaud’s phenomenon, digital ulcers, calcinosis, telangiectasia or any other connective tissue features but was diagnosed with limited cutaneous systemic sclerosis due to ANA & anti-centromere antibody positivity, severe oesophageal dysmotility and diagnosis of mild pulmonary hypertension (on right heart catheter studies).Her main disabling SSs symptom was refractory belching, intermittent dysphagia and reflux disease resulting in poor oral intake and resultant malnutrition. She had 4-week trial of antibiotics to treat for presumptive small intestine bacterial overgrowth (SIBO) due to persistent belching but had no evident improvement. She had multiple endoscopies which only showed grade B oesophagitis due to which she remained on high dose PPI (Omeprazole 40mg BD) but showed no recurrent stricture. She was also given dual therapy with Ranitidine 150mg bd but derived no benefit.In Rheumatology clinic she was started on erythromycin 250 mg BD as a pro-kinetic and in liquid form for better tolerability (due to the dysphagia) with gradual but significant improvement of her upper GI symptoms. Switching liquid form to tablets/capsule form via GP resulted in worsening symptoms so was switched back to liquid form. GI symptoms worsened again in 2017 and impression was tachyphylaxis to erythromycin. She was started on trial of another pro-kinetic (metoclopramide) but symptoms continued worsening. In view of this she was started back on liquid erythromycin and her symptoms gradually improved again and has remained stable since.Discussion/ResultsSystemic sclerosis (SSc) is an incurable connective tissue disorder. It is estimated that approximately 90% of patients with SSc have some form of oesophageal involvement. For first three years, this patient’s main symptoms were her upper GI tract issues with reflux and oesophageal dysmotility causing delayed gastric emptying.Considering the severity of her GI symptoms, it was of great importance for her to maintain a regular follow up with gastroenterology team for a regular review of symptoms and repeat investigations as needed such as multiple repeat UGI endoscopy to ensure no recurrence of oesophageal stricture, monitoring of GORD, and hydrogen breath testing.We recommend for patients with severe oesophageal dysmotility to be started on prokinetics early to control GI symptoms and have minimal impact of these on quality of life. Liquid preparation has shown a significant improvement in symptoms in our patient as compared to tablet or capsule form which actually worsened the symptoms.Key learning points/ConclusionDysphagia can be a presenting symptom of systemic sclerosis in some cases. Upper gastro-intestinal symptoms can be severe with significant effect on quality of life.Management of these symptoms can be challenging and may require a combination of treatments.Pro-kinetics mainly erythromycin can have a major positive impact in controlling GI symptoms,Liquid form had better outcome in this case as compared to tablet or capsule form.Poor control of GI symptoms can result in significant malnutrition which is associated with more aggressive disease progression, so GI symptoms management plays a key role in disease control.

Patients with inflammatory myopathies overlapping with systemic sclerosis: A Brazilian-Japanese bicentric study.

This study aims to describe and compare the demographic, clinical, and laboratory characteristics and follow-up of representative samples of patients with myopathies and systemic sclerosis overlap syndromes (Myo-SSc) from two tertiary centers. This is a cross-sectional and retrospective study conducted between January 2000 and December 2020. Fourty-five patients were analyzed with Myo-SSc (6 males, 39 females; mean age: 50.2±15.4 years; range, 45 to 65 years) from two tertiary centers (n=30 from Brazil and n=15 from Japan). The median follow-up was 98 (range, 37 to 168) months. Muscle impairment started simultaneously with the diagnosis of systemic sclerosis in 57.8% (26/45) of cases. Muscle involvement occurred before the onset of systemic sclerosis in 35.5% (16/45) of cases, and after in 6.7% (3/45). Polymyositis was observed in 55.6% (25/45) of cases, followed by dermatomyositis in 24.4% (11/45) and antisynthetase syndrome in 20.0% (9/45). Concerning systemic sclerosis, the diffuse and limited forms occurred in 64.4% (29/45) and 35.6% (16/45) of the cases, respectively. Comparing the subgroups, Myo or SSc onset was earlier in Brazilian patients, and they had a higher frequency of dysphagia (20/45, [66.7%]) and digital ulcers (27/45, [90%]), whereas Japanese patients had higher modified Rodnan skin scores (15 [9 to 23]) and prevalence of positive anti-centromere antibodies (4/15 [23.7%]). The current disease status and mortality were similar in both groups. In the present study, Myo-SSc affected middle-aged women, and its manifestation spectrum varied according to geographic distribution.

Coxiella burnetii Infection Associated With Thromboangiitis Obliterans-like Phenomena With Digital Autoamputation: A Case Report and Review of Q Fever-Associated Autoimmunity.

We present a case of a patient with chronic Q fever who presented with digital necrosis, autoamputations, and positive anticentromere antibody, mimicking a scleroderma vasculopathy or thromboangiitis obliterans. Coxiella burnetii infection has long been associated with the presence of autoantibodies and autoimmune phenomena including vasculitis. Clinicians should consider Q fever testing in patients with new-onset autoimmune diseases or autoantibodies and appropriate exposure histories.

Ultrasonographic characteristics of major salivary glands in anti-centromere antibody-positive primary Sjögren's syndrome.

To investigate salivary gland ultrasonography (SGUS) findings in primary Sjögren's syndrome (pSS) patients positive for the anti-centromere antibody (ACA) and compare these with those in ACA-negative pSS patients. We analyzed demographic, clinical, laboratory, and SGUS data of pSS patients who fulfilled the 2002 American-European Consensus Group classification criteria for pSS. SGUS findings of four major salivary glands (bilateral parotid and submandibular glands) were scored in five categories and compared between ACA-positive and ACA-negative pSS patients. Linear regression analysis was performed to elucidate the factors associated with SGUS score. In total, 121 pSS patients were enrolled (19, ACA-positive). The ACA-positive patients were older (67.0 vs 58.0 years, P = 0.028), whereas anti-Ro/SSA and anti-La/SSB positivity was more prevalent in the ACA-negative group (89.2% vs 21.1%, P < 0.001, and 47.1% vs 10.5%, P = 0.007, respectively). The total SGUS and hypoechoic area scores were lower in ACA-positive patients (16.0 vs 23.0, P = 0.027, and 4.0 vs 7.0, P = 0.004, respectively). In univariate regression analysis, being positive for unstimulated salivary flow rate (USFR < 1.5 ml/15 min), anti-Ro/SSA, and rheumatoid factor were positively associated whereas ACA positivity was negatively associated with the SGUS score. In multivariate regression analysis, being positive for USFR, anti-Ro/SSA, and rheumatoid factor showed significant association with the SGUS score. ACA-positive pSS patients showed a lower SGUS score than ACA-negative patients, which was especially prominent in the hypoechoic area component.

Persistent eosinophilia and associated organ involvement in Thai patients with systemic sclerosis: Data from the Siriraj scleroderma cohort.

Objectives This study aims to investigate the prevalence of persistent eosinophilia and associated organ complications in Thai patients with systemic sclerosis (SSc).Patients and methods This post-hoc study included 107 adult patients (23 males, 84 females; mean age: 50.4±11.6 years; range, 18 to 79 years) diagnosed with SSc between November 2013 and June 2017. Eosinophilia was defined as an absolute eosinophil count of >500/μL or a percentage count of >7%. Eosinophil levels collected at every visit over one year were categorized as persistently high (PH), persistently low (PL), high-to-low (HL), low-to-high (LH), or variable levels (VL). The study compared variables between PH and non-PH (PL+HL+LH+VL) groups. The patients with baseline eosinophilia were also identified and compared with the non-eosinophilia group.Results The median disease duration was 3.2 years. Of the patients, 79.4% had diffuse cutaneous SSc and 76.7% had anti-Scl-70 positivity. A total of 11.2%, 66.4%, 1.9%, 8.4%, and 12.1% of the patients were categorized into the PH, PL, HL, LH, and VL groups, respectively. Compared to non-PH groups, the PH group had a higher prevalence of anti-centromere antibody (ACA), higher baseline percent predicted total lung capacity, and lower baseline C-reactive protein and creatine phosphokinase (p<0.05 for all). The ACA positivity (odds ratio [OR]: 18.5; 95% confidence interval [CI]: 1.64-208.46) was associated with PH. The patients with baseline eosinophilia (17.8%) had a higher prevalence of non-specific interstitial pneumonia with periodic eosinophilia at the time of diagnosis (100% vs. 6.5%, p<0.0001; OR: 4.667; 95% CI: 1.712-12.724).Conclusion The PH was seldom (11%) in patients with SSc compared to periodic eosinophilia, which was more prevalent (18%). It may be related to ACA positivity and better pulmonary outcomes, whereas periodic eosinophilia may involve interstitial lung disease.

Кальциноз при системній склеродермії: поширеність, клініка, менеджмент, ускладнення

У даному літературному огляді підсумовано сучасні дані щодо епідеміології, патофізіології, діагностики та лікування шкірного кальцинозу у пацієнтів із системною склеродермією (ССД). Проведено аналіз обсерваційних досліджень, що описують частоту кальцинозу при ССД і асоційованих з ним клінічних ознак; молекулярних досліджень, що вивчають потенційні патогенетичні механізми; наведені клінічні випадки, що описують нові діагностичні підходи і методи лікування кальцинозу. Шкірний кальциноз — це відкладення нерозчинного кальцію в шкірі і підшкірних тканинах. Кальциноз — одна з основних, погано керованих клінічних проблем у пацієнтів із ССД, яка зачіпає щонайменше одну четверту частину хворих. Кальциноз асоційований з більшою тривалістю хвороби, дигітальними виразками, акроостеолізом, позитивними антицентромерними і антитопоізомеразними антитілами. Хоча патогенез кальцинозу остаточно невідомий, є докази, що підтверджують роль місцевої хронічної травматизації, хронічного запалення, судинної гіпоксії і дисрегуляції білків кісткового матриксу як потенційних механізмів розвитку цього патологічного стану у пацієнтів із ССД. Діагноз може бути встановлений на основі клінічних даних або за допомогою стандартної рентгенографії. Кілька фармакологічних методів лікування були застосовані у пацієнтів із кальцинозом зі змінними і не такими значущими результатами, у свою чергу, хірургічне видалення депозитів кальцію залишається основним методом лікування.

POS0718 CLINICAL CHARACTERISTICS ASSOCIATED WITH GLANDULAR INVOLVEMENT EVALUATED BY SALIVARY GLAND ULTRASONOGRAPHY IN SJÖGREN’S SYNDROME

Background:Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands, which results in reduced secretory functions and oral and ocular dryness (1). In addition, patients often have extraglandular manifestations, such as interstitial pneumonia and interstitial nephritis, and the appearance of autoantibodies such as anti-Ro/SS-A and La/SS-B antibodies. Salivary gland ultrasonography (SGUS) is typically used to evaluate the findings of salivary glands; thus, we can evaluate the severity of salivary gland disorders due to SS using SGUS in real time (2).Objectives:To identify clinical indices, including disease activity, associated with glandular involvement evaluated using SGUS in patients with SS.Methods:We enrolled patients with SS (n=115) and non-SS sicca subjects (n=90) who visited Nagasaki University Hospital between 1995 and 2019. The patients’ SS classifications were based on the 2002 American–European Consensus Group (AECG) SS classification criteria (3). The non-SS sicca subjects exhibited sicca symptoms but did not fulfill the AECG SS classification criteria. SGUS and clinical indices such as age, sex, the focus score (FS), sicca symptoms, the Saxon test results, Schirmer’s test results, anti-SS-A/Ro antibody positivity, anti-SS-B/La antibody positivity, anti-centromere antibody (ACA) positivity, serum immunoglobulin G levels, and the clinical European League Against Rheumatism SS disease activity index were examined. The ultrasonography (US) score was calculated based on SGUS imaging (hypoechoic area, hyperechoic band, and irregular border) (4).Results:The US score was significantly higher in patients with SS than that in non-SS sicca subjects. In addition, we found significant correlations between the US score and FS in patients with SS. Multivariate analysis revealed the FS, Saxon test positivity, and ACA positivity as the variables independently associated with the US score in patients with SS. These results were the same in the primary SS patient group (n=96). Patients with ACA positivity had significantly higher US scores compared to those in patients with ACA negativity, whereas the FS was not significantly high. In addition, patients with ACA positivity had significantly greater positivity of hyperechoic bands than that in patients with ACA negativity.Conclusion:This study indicated that ACA positivity, which is not reflected in sialadenitis of SS, is associated with the US score in patients with SS. These results suggest that US findings of patients with ACA positivity might show specific changes in salivary glands, such as fibrosis, and not only sialadenitis (5).

Clinical manifestations in anti-Ro52/SS-A antibody-seropositive patients with Sjögren's syndrome

Background: The relationship between anti-Ro52/SS-A antibody (anti-Ro52) and the clinical manifestations of Sjögren's syndrome (SS) has not been fully clarified. We determined the clinical factors relevant to SS patients with anti-Ro52. Methods: We conducted a retrospective study of 149 subjects suspicious for SS and 50 healthy control subjects. We analyzed items of the American-European Consensus Group (AECG) criteria and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results: SS was documented in 115 subjects. Anti-Ro52 was observed in 70 SS patients. Anti-Ro52 positivity showed a significantly higher association with anti-Ro60 positivity than with anti-centromere antibody (ACA) positivity (p < 0.05). Regarding the difference in the anti-Ro52 concentration, we observed six significantly relevant components: two AECG components and four non-AECG components. The anti-Ro52 concentration well-discriminated three clinical factors (ROC AUC >0.75), i.e., ACA seropositivity, ESSDAI score ≥1, and RF, and it moderately discriminated high serum IgG, focus score ≥1, and anti-La/SS-B antibody seropositivity (ROC AUC >0.7). A linear relationship between the ESSDAI score and the anti-Ro52 concentration was observed. Conclusion: A significant association between clinical factors (including the ESSDAI) and the anti-Ro52 concentration were revealed. Anti-Ro52 was more highly associated with anti-Ro60 positivity than with ACA positivity.

The clinical and laboratory features associated with cancer in patients with primary biliary cholangitis: a longitudinal survey-based study.

To analyze the clinical and laboratory features of primary biliary cholangitis (PBC) patients complicated with cancer, and explore the potential factors associated with cancer. We consecutively enrolled PBC patients from January 2002 to February 2016 in Peking Union Medical College Hospital and performed a structured interview, systemic rheumatologic evaluation, and laboratory tests. The risk factors associated with cancer were analyzed with univariate and multivariable logistic regression and proportional hazard model. Among the 580 PBC patients enrolled, 51 cancers were identified in 51 patients (8.8%), including 45 (88.2%) solid tumors and 6 (11.8%) hematologic malignancies. Patients with cancer were older (62.1 ± 9.6 vs. 55.4 ± 11.6 years, p < 0.01) than patients without cancer. Additionally, positive anti-centromere antibody (ACA) was more frequently observed in patients without cancer (25.9% vs 4.3%, p = 0.019) compared with patients with cancer diagnosed after establishing PBC. The median follow-up after the diagnosis of PBC was 4 years (IQR 2.0-6.6). Furthermore, multivariable logistic regression confirmed that older age was associated with cancer in PBC patients (odds ratio (OR) = 1.045, 95% confidence interval (CI): 1.006-1.085), and positive ACA was a protective factor (OR = 0.116, 95% CI: 0.015-0.876). Additionally, proportional hazard model analysis revealed that age was a risk factor (hazard ratio = 1.045, 95% CI: 1.012-1.080), and positive ACA was a protective factor (hazard ratio = 0.232, 95% CI: 0.055-0.977) for cancer. Both solid tumor and hematologic malignancy were prevalent in PBC patients. Older age was associated with cancer, and positive ACA was a protective factor of cancer in PBC patients. Key Points • Patients with PBC could present with both solid tumors and hematologic malignancies. • Multivariable logistic regression and proportional hazard model analysis revealed that age was a risk factor as we know, and positive ACA was a protective factor.