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Abstract Background and Aim High autoimmune hepatitis (AIH) and overlap syndrome (OS) prevalence have been previously documented among Alaska Native people. The purpose of this project is to report changes in AIH/OS prevalence over time, clinical characteristics, and factors associated with biochemical remission. Methods We reviewed medical records for Alaska Native/American Indian (AN/AI) patients diagnosed with AIH/OS between 1984 and 2021. Point prevalence was calculated based on AIH/OS patients alive at the end of 2021 and at 5‐year intervals from July 1, 2000, to July 1, 2020. Results We identified 189 AN/AI persons diagnosed with AIH or OS (157 AIH, 32 OS). Of these 189, 137 were alive at the end of 2021 for a point prevalence of 91.2 per 100 000 (95% confidence interval [CI]: 77.2–107.8)—75.9 (95% CI: 63.2–91.2) for AIH and 15.3 (95% CI: 10.2–23.0) for OS. Prevalence for both AIH and OS has risen steadily since 2000. Eighty‐nine consented participants (62.7%) achieved biochemical remission with a median time from diagnosis to start of remission of 1.9 years (IQR 0.5–5.0 years). Consented patients with fatty liver were less likely to achieve remission, but their time to remission was shorter than for patients without fatty liver. Conclusion The AN/AI population in Alaska continues to have the highest reported prevalence of AIH/OS in the world, with prevalence rising steadily since 2000. High reported AIH/OS prevalence is likely due in part to strong referral networks for liver disease. Detection and treatment can lead to biochemical remission and improved health outcomes.

Overlapping syndrome is a syndrome that meets the criteria for at least two connective tissue diseases. When systemic lupus erythematosus (SLE) overlaps with systemic sclerosis (SSc), dermatomyositis/polymyositis, Sjogren's syndrome (SS), rheumatoid arthritis (RA), and other diseases, the lack of specific serological indicators and clinical manifestations can result in missed diagnosis and/or misdiagnosis, leading to life-threatening in severe cases. Early diagnosis and treatment of overlap syndrome can help alleviate the impact on patients′ quality of life and improve the prognosis. This article reviews the research progress in this disorder and its management strategies. Although there is currently limited research on SLE related overlap syndrome, its clinical manifestations and immunological characteristics are strongly related to the overlapping diseases. Specific tests and examinations in time can facilitate the diagnosis and treatment of overlap syndrome.

Аim: to evaluate the state of small intestine permeability by the “double sugar test” in patients with overlap syndrome (autoimmune hepatitis / primary biliary cholangitis (AIH / PBC)).Materials and methods. Prospectively, 56 people were included in the study. Of these, 26 were diagnosed with AIH/PBC, 30 were in the control group. The diagnosis was made in accordance with the current recommendations. The average age of patients was 49.7 ± 13.8 years, healthy volunteers — 48.6 ± 9.2 years. The determination of the permeability of the small intestine was carried out by a “double sugar test” (the ratio of lactulose/mannitol in urine), using the method of high-performance liquid chromatography — mass spectrometry.Results. In patients with AIH/PBC, an increase in intestinal permeability was found — 0.20 [0.09; 0.30] (p < 0.001) compared with the control group 0.01 [0.01; 0.02]. We divided patients at the stage of liver damage. An increased small intestinal permeability was revealed: hepatitis stage — 0.19 [0.13; 0.30] (p < 0.001), liver cirrhosis stage — 0.18 [0.09; 0.30] (p < 0.05) compared with the control group. In the early stages of disease (1 month from the onset of the disease) had an increased lactulose/mannitol ratio — 0.13 [0.05; 0.26] (p < 0.001) compared to the control group. In the presence of portal hypertension (PH), small intestinal permeability was increased — 0.18 [0.09; 0.30] (p < 0.001) compared with the control group.Conclusions. An increase in small bowel permeability was found in patients with overlapping syndrome. All patients had increased intestinal permeability (regardless of the presence of extrahepatic manifestations).

Background & Aims: Long-term follow-up studies of paediatric onset autoimmune liver disease (AILD) are invaluable in helping better understand the clinical course of disease. In day-to-day practice clinicians struggle with disease definitions whilst patients and parents lack clear prognostic information. Methods: The clinical progression of 159 patients with childhood onset AILD between June 1990 and December 2013 was reviewed, capturing data up to adulthood (ending May 2021). Results: Presentation with autoimmune hepatitis (AIH) was dominant (n = 119); biliary presentations accounted for 25%. During follow up, biliary disease progression confirmed by cholangiography and/or liver histology was observed frequently: 19.8% (20/101) patients with childhood onset AIH type 1 (AIH-1) developed biliary features by adulthood and of these 50% phenotypically transitioned to primary sclerosing cholangitis (PSC); the remaining transitioned to an overlap disease phenotype. No patients with AIH type 2 developed biliary progression. Two-thirds of patients with overlap features (14/21) in childhood had phenotypically progressed to PSC by adulthood. Approximately 43% (6/14) of AIH-1 patients requiring a liver transplant in adulthood had explant evidence of biliary disease compared with 11% (1/9) in childhood, whereas 35.7% (5/14) of patients had histology diagnostic of PSC in their explant liver and 7.1% (1/14) had overlap features. All patients with biliary phenotypes (PSC, autoimmune sclerosing cholangitis, overlap) who required a transplant (n = 18) were found to have explant histology consistent with PSC. Twelve of 14 patients with biliary progression developed ulcerative colitis during follow-up with 92% progressing to PSC. Conclusions: Three decades of follow-up demonstrated how children presenting with AILD had a significant risk of clinical transformation to PSC. Biliary progression was significantly associated with the development of inflammatory bowel disease. Impact and implications: Childhood onset autoimmune liver disease remains very impactful for patients and families. Disease nomenclature can however be confusing. Long-term follow up studies as children become adults is important to help understand how and why disease behaves over time. Understanding more about the long-term course of childhood autoimmune liver disease will help patients, families and doctors striving to improve care and reduce poor clinical outcomes. We followed over 150 patients with childhood onset autoimmune liver diseases into adulthood. We found that amongst patients with classical autoimmune hepatitis, 1 in 5 developed biliary disease over time, mostly consisting of primary sclerosing cholangitis. This was associated with developing inflammatory bowel disease. Our study design was retrospective and has relevant limitations. Defining phenotypes of autoimmune liver diseases is difficult and there is insufficient consensus, especially between adult and childhood physicians. Our data confirms the critical importance of careful long-term follow-up of patients, including safe transition to adult care, as well as robustly demonstrates, using real-world data, how disease nature can change over time. Our study affirms the need for investment in prospective cohort studies.

Autoimmune encephalitis (AE) has been increasingly recognized in children. An 11-year-old Saudi boy presented with prodromal symptoms of fever and headache followed by behavioral changes, cognitive impairment, and focal seizures. Cerebrospinal fluid (CSF) analysis showed pleocytosis. Brain magnetic resonance imaging showed T2/fluid-attenuated inversion recovery hyperintensities involving the temporal, parietal and frontal lobes. Electroencephalography revealed diffuse encephalopathy and electrographic seizures. AE was suspected; intravenous methylprednisolone and immunoglobulin were administered. Autoantibodies against glutamic acid decarboxylase-65 were detected in his serum and CSF and against Sry-like high- mobility group box 1 in his serum only. The patient was diagnosed with seropositive AE and favorably responded to intensive immunosuppressive therapy.

BACKGROUND: Overlap syndrome is a condition in which a patient experiences symptoms that correspond to two or more of these classification standards. More commonly, the overlap is limited to one or more manifestations of each disease. Sjögren's syndrome is a systemic autoimmune disease characterized by the presence of a dry syndrome, primarily xerostomia and xerophthalmia, originating from dysfunction of exocrine glands. Conversely, systemic sclerosis is a rare autoimmune disease characterized by fibrosis development in the skin, internal organs, and vasculopathies. THE CASE: Our case report presents a 62-year-old woman with a history of Sjögren's syndrome, who exhibited symptoms of xerostomia, xerophthalmia, xerodermia, and had anti-Ro antibodies exceeding 200, along with ultrasound findings of chronic sialadenitis. The patient was under treatment with hydroxychloroquine, pilocarpine, and deflazacort. She attended the rheumatology outpatient clinic for routine follow-up of her disease. During the evaluation, bilateral sclerodactyly and "salt and pepper" lesions on the limbs were observed, along with two reports of ANA with titers of 1:2650 and a centromere pattern. Due to suspicion of coexistence of limited systemic sclerosis, anticentromere antibodies were requested, yielding a positive result, while anti-Scl 70 antibodies were negative. This confirmed the diagnostic suspicion, and azathioprine 50 mg every 12 hours and colchicine 0.5 mg daily were added to her therapy. CONCLUSION: Although Sjögren's syndrome and systemic sclerosis can manifest independently, in certain instances, both conditions overlap. It is worth noting that among the various overlap syndromes related to connective tissue diseases, this overlap is infrequent. However, within connective tissue diseases, systemic sclerosis tends to exhibit overlap more frequently, reported in up to 20-30% of cases. In cases of connective tissue diseases, consideration should always be given to overlap syndromes, involving a meticulous physical examination and careful assessment of laboratory results to avoid overlooking conditions that may negatively impact patients' future quality of life.

Background: Patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome have a worse prognosis compared to AIH or PBC alone and accurately predicting the severity and dynamically monitoring the progression of disease are therefore essential. We aimed to develop a nomogram-based model to predict advanced liver fibrosis in patients with AIH-PBC overlap syndrome. Methods: A total of 121 patients with AIH-PBC overlap syndrome were retrospectively included and randomly assigned to a development set and a validation set. Backward stepwise regression's best model with the lowest AIC was employed to create a nomogram. Diagnose accuracy was evaluated using the area under the receiver operator characteristic curve (AUROC), calibration analysis, and decision curve analysis (DCA) and was compared with aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors-4 (FIB-4) score. Results: The median age of patients was 53.0 years (IQR: 46.0–63.0), and female patients accounted for 95.0 %. Platelets, globulin, total bilirubin, and prothrombin time were associated with advanced fibrosis (≥S3) and used to construct an AIH-PBC overlap syndrome fibrosis (APOSF)-nomogram (available online at https://ndth-zzy.shinyapps.io/APOSF-nomogram/). The AUROCs of APOSF-nomogram were 0.845 (95 % CI: 0.754–0.936) and 0.843 (95 % CI: 0.705–0.982) in development set and validation set respectively, which was significantly better than APRI and FIB-4. Calibration revealed that the estimated risk fits well with biopsy-proven observation. DCA outperformed APRI and FIB4 in terms of net benefit, demonstrating clinical utility. Conclusion: This novel non-invasive web-based online APOSF-nomogram provided a convenient tool for identifying advanced fibrosis in patients with AIH-PBC overlap syndrome. Further prospective, multicenter studies with large sample size are necessary to validate the applicability of APOSF-nomogram.

Background: The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is known as overlap syndrome, and both conditions share common risk factors and are associated with co-morbidities and poor outcomes. Methodology: Sixty stable COPD patients were included in the study. We assessed body measurements, pulmonary functions to diagnose and assess COPD severity, arterial blood gases, STOB-BANG questionnaire (SBQ), Epworth sleepiness scale (ESS), and polysomnography (PSG) for diagnosis and classification of OSA severity. The aim of the study is to assess predictors of OSA among COPD patients. Results: The prevalence of overlap syndrome was 70% among studied stable COPD patients, with a male-to-female ratio of 2:1, and SBQ and ESS were statistically higher in overlap syndrome with p values < 0.001 and 0.002, respectively. Oxygen desaturation index (ODI) was 42.72 ± 30.02 for overlap in comparison to 13.18 ± 5.80 for COPD with a significant p value of < 0.001, and T90 was significantly increased in the overlap group (26.75 ± 10.37) than the COPD-only group (1.8 ± 0.98, p value ≤ 0.001). We found a direct correlation between the GOLD stage and severity of OSA in overlap syndrome. The best cutoff value for the detection of overlap syndrome was ESS = 9 (sensitivity = 88.6% and specificity = 62.5%) and SBQ = 5 (sensitivity = 63.6% and specificity = 93.8%). Conclusion: Overlap syndrome represents 70% of stable COPD patients. A direct relation was found between the GOLD stage and OSA severity in overlap syndrome. ESS and SBQ can be used for screening for OSA in COPD patients but with a lower cutoff value than those used for the general population. Trial registration: Retrospectively registered, registration number is NCT05605431, date of registration October 29, 2022. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Methods: We performed a case–control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age‐, sex‐, BMI‐ and ethnicity‐matched controls. Next, we performed a systematic review and proportional meta‐analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 [AIH]; 20 August 2022 [PBC]; 11 November 2022 [PSC]). The pooled prevalence of diabetes was calculated using an inverse method random effects model. Results: Three hundred twenty‐eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%–5.7%), 1.7% (0.9%–3.1%), 3.1% (1.9%–4.8%) and of T2D 14.8% (11.1%–19.5%), 18.1% (14.6%–22.2%), 6.3% (2.8%–13.3%) in patients with AIH, PBC and PSC, respectively. Conclusions: Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the Foxp3 gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA). ANA are serological hallmarks of several autoimmune disorders including autoimmune liver diseases (AILD). However, the underlying pathogenesis and the role of Treg in AILD remain to be elucidated. The present study therefore aimed to characterize the liver disease in scurfy mice. Methods: Sera from scurfy mice were screened for ANA by indirect immunofluorescence assay (IFA) and tested for a wide range of AILD-associated autoantibodies by enzyme-linked immunosorbent assay, line immunoassay, and addressable laser bead immunoassay. CD4+ T cells of scurfy mice were transferred into T cell-deficient B6/nude mice. Monoclonal autoantibodies from scurfy mice and recipient B6/nudemice were tested for ANA by IFA. Liver tissue of scurfy mice was analyzed by conventional histology. Collagen deposition in scurfy liver was quantified via hepatic hydroxyproline content. Real-time quantitative PCR was used to determine fibrosis-related hepatic gene expression. Hepatic immune cells were differentiated by flow cytometry. Results: All scurfy mice produced ANA. AILD-associated autoantibodies, predominantly antimitochondrial antibodies, were detected at significantly higher levels in scurfy sera. CD4+ T cells from scurfy mice were sufficient to induce anti-dsDNA autoantibodies and ANA with an AILD-related nuclear envelope staining pattern. Liver histology revealed portal inflammation with bile duct damage and proliferation, as in primary biliary cholangitis (PBC), and interface hepatitis with portal-parenchymal necroinflammation, as found in autoimmune hepatitis (AIH). In scurfy liver, TNFa and fibrosis-related transcripts including Col1a1, Timp1, Acta2, Mmp2, and Mmp9 were upregulated. The level of proinflammatory monocytic macrophages (Ly-6Chi) was increased, while M2-type macrophages (CD206+) were downregulated compared to wildtype controls. Despite severe hepatic inflammation, fibrosis did not develop within 25 days, which is close to the lifespan of scurfy mice. Discussion: Our findings suggest that Treg-deficient scurfy mice spontaneously develop clinical, serological, and immunopathological characteristics of AILD with overlapping features of PBC and AIH. [ABSTRACT FROM AUTHOR]

Background and Objectives: Evidence shows that COPD-OSA overlap syndrome (OS) is more frequently accompanied by cardiovascular disease (CVD) in comparison to either disease alone. The aim of the study was to explore whether patients with OS have a higher burden of subclinical myocardial injury and wall stress compared with OSA patients. Materials and Methods: Consecutive patients, without established CVD, underwent polysomnography and pulmonary function testing, due to suspected sleep-disordered breathing. An equal number of patients with OS (n = 53, with an apnea hypopnea index (AHI) > 5/h and FEV1/FVC < 0.7) and patients with OSA (n = 53, AHI > 5/h and FEV1/FVC > 0.7) were included in the study. The detection of asymptomatic myocardial injury and wall stress was performed via the assessment of serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), respectively. Results: OS patients were older (p < 0.001) and had worse hypoxemic parameters, namely average oxyhemoglobin saturation (SpO2) (p = 0.002) and time spent with SpO2 < 90% (p = 0.003) during sleep as well as daytime pO2 (p < 0.001), than patients with OSA. No difference was observed between groups in terms of Epworth Sleepiness Scale (p = 0.432) and AHI (p = 0.587). Both levels of hs-cTnT (14.2 (9.1–20.2) vs. 6.5 (5.6–8.7) pg/mL, p < 0.001) and NT-proBNP (93.1 (37.9–182.5) vs. 19.2 (8.3–35.4) pg/mL, p < 0.001) were increased in OS compared to OSA patients. Upon multivariate linear regression analysis, levels of NT-proBNP and hs-cTnT correlated with age and average SpO2 during sleep. Conclusions: Our study demonstrated higher levels of hs-cTnT and NT-proBNP in OS patients, indicating an increased probability of subclinical myocardial injury and wall stress, compared with OSA individuals. [ABSTRACT FROM AUTHOR]

The overlap syndrome indicates an association between autoimmune hepatitis (AIH) and sclerosis cholangitis or primary biliary cholangitis (PBC). We report a case of a 32-year-old patient who experienced overlap syndrome ten days after receiving the first dose of the mRNA Coronavirus disease-2019 (COVID-19) vaccine. Liver biopsy showed primarily AIH and "overlap syndrome" for PBC. Serum IgG was elevated, and ANA (1/100) and anti-mitochondrial antibody was positive. The patient's treatment plan included prednisolone, ursodeoxycholic acid and azathioprine. Overlap syndrome related to the mRNA COVID-19 vaccines is a very rare entity. After the histopathological diagnosis of the patient, remission was achieved following treatment. [ABSTRACT FROM AUTHOR]

Methods: In this observational study from October 2018 to August 2020, we included all the patients of MCTD and overlap syndromes. Alarcon–Segovia criteria was used as defining criteria for MCTD patients while the patients meeting diagnostic criteria for more than 1 of 6 classical autoimmune rheumatic diseases were selected in the overlap syndromes group. We compared their clinical features, laboratory parameters, and autoantibody profiles. MS Excel, STATA were used for statistical analysis, and comparison between the groups was done with t-test, Chi-square test, and Wilcoxon rank sum test. P < 0.05 was considered as statistically significant. Results: The study consisted of 60 consecutive patients (MCTD, n = 30 and overlap syndromes, n = 30) with higher female population in both groups (90% in MCTD and 84% in the overlap syndromes group) compared to males. The incidence of fever (83.3% vs. 46.6%), weight loss (60% vs. 26.6%), trigeminal neuralgia (76.6% vs. 13.3%), and myositis (63.3% vs. 20.0%) was significantly higher in MCTD than overlap syndromes whereas the incidence of cough (66.6% vs. 90.0%) and dry mouth (20.0% vs. 53.3%) was higher in overlap syndromes than MCTD (P < 0.05). Anti-U1 RNP antibodies were seen in all MCTD (100.0%) patients while anti-Scl 70 antibodies (60%) and anti-ribosomal-p-protein antibodies (13.3%) were seen in overlap syndromes. Conclusion: Fever and weight loss, trigeminal neuralgia, and myositis were more common in MCTD than overlap syndromes. Anti-U1 RNP antibodies seen in MCTD while Anti-Scl 70 antibodies and anti-ribosomal-P antibodies were commonly were seen in overlap syndromes. [ABSTRACT FROM AUTHOR]

Abstract Background Overlap syndrome between primary biliary cholangitis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only few published cases so far in the literature. We highlight here the rarity of this condition and indicate the importance of its recognition. Case presentation We report two cases showing the manifestations of both primary biliary cholangitis and primary sclerosing cholangitis in two Tunisian female patients aged 74 and 42 years, respectively. The first case is a woman who was initially diagnosed with decompensated cirrhosis. Magnetic resonance cholangiopancreatography showed multiple strictures of the common bile duct, and histological findings led to the diagnosis of primary biliary cholangitis/primary sclerosing cholangitis. She was successfully treated with ursodeoxycholic acid. The second case is a middle-aged woman, suffering from primary biliary cholangitis and who was treated with ursodeoxycholic acid. At her 12 month follow-up appointment, she presented with a partial clinical and biochemical response. Tests showed normal thyroid function, liver autoimmune tests for autoimmune hepatitis were negative, and celiac disease markers were also negative. The diagnosis of overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis was finally made on the results of magnetic resonance cholangiopancreatography that showed multiple strictures of the common as well as intrahepatic bile ducts. The patient was put on ursodeoxycholic acid at a higher dose. Conclusions Our cases raise awareness for this rare condition and indicate the importance of recognizing a possible overlap syndrome, especially in patients with primary biliary cholangitis, to optimize treatment. We suggest considering the overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis when a patient presents with the diagnostic criteria of both diseases.

Prinpat Pinyowiwat, Suthinee Rutnin, Kumutnart Chanprapaph Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Kumutnart Chanprapaph, Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Road, Ratchatewi, Bangkok, 10400, Thailand, Tel +662-201-1141, Fax +662-201-1211, Email kumutnartp@hotmail.comAbstract: Sclerodermic or scleroderma-like lupus erythematosus panniculitis (SLEP) shares both clinical and histopathological features between lupus panniculitis and localized scleroderma. It is exceedingly rare. We herein report a case of SLEP manifested with a solitary, firm-to-hard, erythematous plaque in an Asian woman. This patient responded well to intralesional corticosteroid and antimalarials. We have reviewed the pathogenesis of fibrosis in patients with chronic cutaneous lupus erythematosus as well as documented cases of SLEP in the literature.Keywords: cutaneous lupus erythematosus, scleroderma-like lupus erythematosus panniculitis, sclerodermic lupus panniculitis, localized scleroderma, lupus profundus, overlap syndrome

Abstract Background and objective The aim of this study was to elucidate the clinical and myopathological characteristics of patients with anti-signal recognition particle (SRP) positive immune-mediated necrotizing myopathy (IMNM) overlap Sjogren’s syndrome (SS). Materials and methods We retrospectively analyzed the data of anti-SRP positive IMNM patients admitted in the Neurology Department of Tongji Hospital between January 2011 to December 2020. Patients were divided into two groups: anti-SRP IMNM overlap SS group and anti-SRP IMNM control group. The clinical features, laboratory results, histological features, treatment, and prognosis were compared between the two groups. Results A total of 30 patients with anti-SRP IMNM were included, including six anti-SRP IMNM overlap SS patients (two males, four females), with a median age of 39 years, and 24 anti-SRP IMNM patients (ten males, fourteen females), with a median age of 46 years. The anti-SRP IMNM overlap SS group had a lower prevalence of muscle atrophy (0 vs 50%, p = 0.019), and a higher prevalence of extramuscular manifestations, including cardiac abnormalities and ILD (Interstitial lung disease). CD4 + and CD68 + inflammatory infiltrations were significantly increased in anti-SRP IMNM overlap SS patients, with an increased presence of CD4 + cells in both necrotic(p = 0.023) and endomysial areas (p = 0.013), and more CD68 + cells (p = 0.016) infiltrated the endomysial area. Deposition of membrane attack complex (MAC) on sarcolemma (p = 0.013) was more commonly seen in the anti-SRP IMNM overlap SS group. Conclusion Our data revealed that anti-SRP IMNM-SS overlap patients may present with milder muscular manifestation, but worse extramuscular manifestations compared to anti-SRP IMNM patients without SS. CD4 + and CD68 + inflammatory infiltrations and MAC deposition were remarkably increased in anti-SRP IMNM-SS overlap patients.

Abstract Introduction Patients with overlap syndrome (OS), that is obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), are at increased risk of acute exacerbations related to COPD (AECOPD). We assessed the effect of CPAP compliance on AECOPD, symptoms and pulmonary function in OS patients. Methods Consecutive OS patients underwent assessment at baseline and at 12 months under treatment with CPAP of: AECOPD and hospitalizations, COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) questionnaires, pulmonary function testing and 6‐min walking test (6MWT). Results In total, 59 patients (54 males) with OS were followed for 12 months and divided post hoc according to CPAP compliance into: group A with good (≥4 h CPAP use/night, n = 29) and group B with poor (

Overlap syndrome (OVS) is a distinct clinical entity that seems to result in potential cardiovascular consequences. We aimed to estimate the prevalence and risk factors for OVS in OSA patients and analyze clinical and PSG characteristics associated with OVS. In this cross-sectional study, 2616 patients evaluated for OSA underwent type-1 polysomnography (PSG). They were grouped as pure OSA (AHI > 15/h) and OVS patients. Demographics, PSG data, pulmonary function tests and arterial blood gases (ABGs) were compared between groups after adjustments for confounders. OSA was diagnosed in 2108 out of 2616 patients. Of those, 398 (19%) had OVS. Independent predictors of OVS were older age [OR: 5.386 (4.153–6.987)], current/former smoking [OR: 11.577 (7.232–18.532)], BMI [OR: 2.901 (2.082–4.044)] and ABG measurements [PaCO2 ≥ 45 OR: 4.648 (3.078–7.019), PO2 [OR: 0.934 (0.920–0.949)], HCO3− [OR: 1.196 (1.133–1.263), all p < 0.001]. OVS was also associated with prevalent hypertension [OR: 1.345 (1.030–1.758), p = 0.03] and cardiovascular disease [OR: 1.617 (1.229–2.126), p < 0.001], depressive symptoms [OR: 1.741 (1.230–2.465), p = 0.002] and nocturia [OR: 1.944 (1.378–2.742), p < 0.001], as well as with indices of OSA severity. Disturbances in sleep architecture were more prominent in OVS expressed by lower %N3 and REM% and higher arousal index. Our data suggest that OVS is prevalent among OSA patients, with distinct clinical and PSG characteristics. These characteristics could be utilized as predictive factors for early identification and further evaluation of these patients towards desirable patient-reported outcomes.

Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is implemented in selected rapidly progressive SSc with a high risk of organ failure. However, existing guidelines are based on clinical trials that do not represent the entire patient population and exclude critically ill patients with no therapeutic alternatives. Examples of AHSCT in IgG4-RD are absent. We report the case of a 44-year-old female patient with overlapping progressive diffuse SSc and sinonasal IgG4-RD. After 11 years of ineffective SSc treatment, AHSCT was performed. The 63-month follow-up showed a regression of SSc symptoms. AHSCT was not intended as treatment in the case of IgG4RD, although the first symptoms of the disease developed before transplantation. The sinus lesions progressed after AHSCT and remained indolent only after surgical treatment (bilateral ethmoidectomy, sphenoidotomy, intranasal buccal antrostomy), which allowed histopathological confirmation of IgG4-RD.

IntroductionScurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the Foxp3 gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA). ANA are serological hallmarks of several autoimmune disorders including autoimmune liver diseases (AILD). However, the underlying pathogenesis and the role of Treg in AILD remain to be elucidated. The present study therefore aimed to characterize the liver disease in scurfy mice.MethodsSera from scurfy mice were screened for ANA by indirect immunofluorescence assay (IFA) and tested for a wide range of AILD-associated autoantibodies by enzyme-linked immunosorbent assay, line immunoassay, and addressable laser bead immunoassay. CD4+ T cells of scurfy mice were transferred into T cell-deficient B6/nude mice. Monoclonal autoantibodies from scurfy mice and recipient B6/nude mice were tested for ANA by IFA. Liver tissue of scurfy mice was analyzed by conventional histology. Collagen deposition in scurfy liver was quantified via hepatic hydroxyproline content. Real-time quantitative PCR was used to determine fibrosis-related hepatic gene expression. Hepatic immune cells were differentiated by flow cytometry.ResultsAll scurfy mice produced ANA. AILD-associated autoantibodies, predominantly antimitochondrial antibodies, were detected at significantly higher levels in scurfy sera. CD4+ T cells from scurfy mice were sufficient to induce anti-dsDNA autoantibodies and ANA with an AILD-related nuclear envelope staining pattern. Liver histology revealed portal inflammation with bile duct damage and proliferation, as in primary biliary cholangitis (PBC), and interface hepatitis with portal-parenchymal necroinflammation, as found in autoimmune hepatitis (AIH). In scurfy liver, TNFα and fibrosis-related transcripts including Col1a1, Timp1, Acta2, Mmp2, and Mmp9 were upregulated. The level of proinflammatory monocytic macrophages (Ly-6Chi) was increased, while M2-type macrophages (CD206+) were downregulated compared to wildtype controls. Despite severe hepatic inflammation, fibrosis did not develop within 25 days, which is close to the lifespan of scurfy mice.DiscussionOur findings suggest that Treg-deficient scurfy mice spontaneously develop clinical, serological, and immunopathological characteristics of AILD with overlapping features of PBC and AIH.

The phenotypic spectrum of myelin oligodendrocyte glycoprotein (MOG)- IgG-associated disorders (MOGAD) has broadened in the past few years, and atypical phenotypes are increasingly recognized. Isolated seizures and MRI-negative brainstem and cerebellar symptoms or encephalitis have rarely been reported as a feature of MOGAD and represent a diagnostic challenge. Meanwhile, the coexistence of MOG IgG and other CNS autoimmune antibodies is infrequent. We report a patient presented with isolated epileptic onset, relapsed with MRI-negative brainstem symptoms and MRI-negative encephalitis. He was positive for MOG IgG throughout the disease course while concomitant NMDAR IgG was not detected positive until second relapse. He showed decreasing response to conventional first-line therapy. The last relapse was during a COVID-19 epidemic with limited inpatient resources. Fortunately, he was ultimately controlled on subcutaneous ofatumumab, a novel fully humanized anti-CD20 mAb. This is the first report about subcutaneous ofatumumab treatment in MOG and NMDAR IgG double positive encephalitis with 12-month follow-up, depicting its potential as a therapeutic option. [ABSTRACT FROM AUTHOR]

Autoimmune liver diseases are siloed into three syndromes that define clinical practice. These classifiers can, and are, challenged by variant presentations across all ages, something inevitable to disease definitions that rely on interpreting (inherently variable) semi-quantitative/qualitative clinical, laboratory, pathological or radiological findings. Furthermore this categorisation is premised on an ongoing absence of definable disease aetiologies. Clinicians thus encounter individuals with biochemical, serological, and histological manifestations that are common to both primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH), often labelled as 'PSC/AIH-overlap'. In childhood the term 'autoimmune sclerosing cholangitis (ASC)' may be used, and some propose this to be a distinct disease process. In this article we champion the concept that ASC and PSC/AIH-overlap are not distinct entities. Rather, they represent inflammatory phases of PSC frequently manifesting earlier in the disease course, most notably in younger patients. Ultimately, disease outcomes remain similar to those of a more classical PSC phenotype observed in later life. Thus, we argue that it is now time to align disease names and descriptions used by clinicians across all patient subpopulations, to help unify care. This will enhance collaborative studies and ultimately contribute to rational treatment advances. [ABSTRACT FROM AUTHOR]

La sclérodermie systémique (ScS) est une maladie auto-immune rare touchant principalement la femme entre 40 et 60 ans. Elle se caractérise par une fibrose cutanée et viscérale, une altération du réseau microvasculaire et la présence d'auto-anticorps. La ScS peut être associée à une autre connectivite ou à d'autres maladies auto-immunes définissant ainsi le syndrome de chevauchement. L'objectif de notre étude est de décrire ces syndromes de chevauchement. Nous avons analysé les données d'une cohorte rétrospective et bicentrique (unité de médecine interne de l'hôpital Nord de Marseille et unité de médecine interne de l'hôpital d'instruction des Armées Sainte-Anne à Toulon) de patients suivis pour une ScS entre le 1er janvier 2019 et le 1er décembre 2021. Nous avons recueilli leurs caractéristiques cliniques, immunologiques, les maladies auto-immunes et inflammatoires associées ainsi que la morbi-mortalité. La cohorte incluait 151 patients dont 134 étaient des ScS cutanées limitées. Cinquante-deux (34,4 %) patients présentaient au moins une atteinte auto-immune ou inflammatoire associée. L'association de deux connectivites dont la ScS concernait 24 patients (15,9 %) avec un tiers de syndrome de Sjögren et un tiers de myosite auto-immune. La principale maladie auto-immune associée à la ScS était la thyroïdite auto-immune, retrouvée chez 17 patients (11,3 %). La survenue de complications (recours à l'hospitalisation, oxygénothérapie au long cours, décès) n'était pas significativement différente en fonction de l'existence d'un syndrome de chevauchement ou non. La ScS s'accompagne souvent d'autres pathologies auto-immunes. Cette intrication de pathologies associées, modifiant parfois l'évolution de la ScS, impose un suivi personnalisé. Systemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. We have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. The cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. SSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up. [ABSTRACT FROM AUTHOR]

A 60-year-old man with type-2 diabetes and chronic hepatitis C (HCV) was diagnosed with single hepatocellular carcinoma (HCC) of 67 mm in the hepatic posterior right lobe. Lenvatinib 8 mg was initiated but discontinued because of grade 3 liver injury. The patient continued to have prolonged liver injury and persistently high immunoglobulin G levels. Antinuclear antibody titer increased from 1:40 to 1:320. Histopathological examination of a liver biopsy specimen revealed interface hepatitis with lymphocyte and plasma cell infiltration, rosette formation, and emperipolesis, suggesting the possibility of autoimmune hepatitis (AIH). First, treatment with prednisolone was initiated; however, the response was poor. After starting glecaprevir/pibrentasvir (GLE/PIB) as direct-acting antivirals (DAA), HCV RNA rapidly disappeared, and serological liver function improved. After confirmation of sustained virological response 24, HCC recurrence was observed, and partial hepatectomy was performed. Background liver findings showed that liver parenchymal inflammation improved compared with that before DAA treatment. This is the first case of HCV-AIH overlap syndrome treated with DAA using GLE/PIB. Liver function improved within a short treatment period of 8 weeks, as confirmed using serology and histology. [ABSTRACT FROM AUTHOR]

Background and Aim: High autoimmune hepatitis (AIH) and overlap syndrome (OS) prevalence have been previously documented among Alaska Native people. The purpose of this project is to report changes in AIH/OS prevalence over time, clinical characteristics, and factors associated with biochemical remission. Methods: We reviewed medical records for Alaska Native/American Indian (AN/AI) patients diagnosed with AIH/OS between 1984 and 2021. Point prevalence was calculated based on AIH/OS patients alive at the end of 2021 and at 5‐year intervals from July 1, 2000, to July 1, 2020. Results: We identified 189 AN/AI persons diagnosed with AIH or OS (157 AIH, 32 OS). Of these 189, 137 were alive at the end of 2021 for a point prevalence of 91.2 per 100 000 (95% confidence interval [CI]: 77.2–107.8)—75.9 (95% CI: 63.2–91.2) for AIH and 15.3 (95% CI: 10.2–23.0) for OS. Prevalence for both AIH and OS has risen steadily since 2000. Eighty‐nine consented participants (62.7%) achieved biochemical remission with a median time from diagnosis to start of remission of 1.9 years (IQR 0.5–5.0 years). Consented patients with fatty liver were less likely to achieve remission, but their time to remission was shorter than for patients without fatty liver. Conclusion: The AN/AI population in Alaska continues to have the highest reported prevalence of AIH/OS in the world, with prevalence rising steadily since 2000. High reported AIH/OS prevalence is likely due in part to strong referral networks for liver disease. Detection and treatment can lead to biochemical remission and improved health outcomes. [ABSTRACT FROM AUTHOR]

The SCN5A-1795insD founder variant is a unique SCN5A gene variant found in a large Dutch pedigree that first came to attention in the late 1950s. To date, this is still one of the largest and best described SCN5A founder families worldwide. It was the first time that a single pathogenic variant in SCN5A proved to be sufficient to cause a sodium channel overlap syndrome. Affected family members displayed features of Brugada syndrome, cardiac conduction disease and long QT syndrome type 3, thus encompassing features of both loss and gain of sodium channel function. This brief summary takes us past 70 years of clinical experience and over 2 decades of research. It is remarkable to what extent researchers and clinicians have managed to gain understanding of this complex phenotype in a relatively short time. Extensive clinical, genetic, electrophysiological and molecular studies have provided fundamental insights into SCN5A and the cardiac sodium channel Nav1.5. [ABSTRACT FROM AUTHOR]

Background and objectives: Obstructive sleep apnea-hypopnea syndrome (OSAHS) and chronic obstructive pulmonary disease (COPD) are independently linked to an increase in cardiovascular disease (CVD). Only a few studies have been published linking the association between overlap syndrome and congestive heart failure (CHF). This review highlights the interplay between overlap syndrome (OSAHS-COPD) and CHF. Materials and methods: We thoroughly reviewed published literature from 2005 to 2022 in PubMed, Google Scholar, and Cochrane databases to explore the link between overlap syndrome and cardiovascular outcomes, specifically congestive heart failure. Results: Research indicates that individuals with overlap syndrome are more likely to develop congestive heart failure than those with COPD or OSA alone. Congestive heart failure is a common comorbidity of overlap syndrome, and it has a two-way connection with sleep-related breathing disorders, which tend to occur together more frequently than expected by chance. Conclusions: CHF seems to have a strong relationship with OS. Further research is required to understand the relationship between OS and CHF. [ABSTRACT FROM AUTHOR]

A close relationship between inflammatory bowel diseases (IBD) and hepatobiliary disorders, such as autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC), is well established. Hepatobiliary manifestations occur in 30% of patients with IBD, and 5% develop chronic liver disease. The spectrum of symptoms of the overlap syndrome ranges from asymptomatic elevated liver function tests to serious diseases. The pathogenesis of liver complications in IBD is not fully recognized. It may either have an autoimmune background or be caused by intestinal inflammation, metabolic impairment, or drug toxicity. The aim of this review is to summarize AIH and PSC overlap syndrome in IBD. [ABSTRACT FROM AUTHOR]

Introduction and aim. Autoimmune rheumatic diseases are a group of disorders with similar clinical, laboratory and immunological manifestations. Connective tissue diseases include systemic scleroderma, dermatomyositis or polymyositis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus. If the patient meets the diagnostic criteria for at least two of these diseases and has specific serologic markers, a diagnosis of overlap syndrome is possible. Description of the case. This case describes a 27-year-old man who had a history of paroxysmal fever, night sweats, erythema- like skin lesions on the forearms and lower legs, a feeling of progressive muscle weakness especially in the proximal muscles, and dry mouth. The patient was diagnosed with an overlap syndrome: systemic lupus erythematosus, dermatomyositis, and Sjögren's syndrome. Conclusion. Overlap syndrome is difficult to treat due to its multisystem nature, requiring a symptomatic therapeutic approach and careful control of medication doses to reduce side effects while controlling disease activity. [ABSTRACT FROM AUTHOR]

Overlapping syndrome is a syndrome that meets the criteria for at least two connective tissue diseases. When systemic lupus erythematosus(SLE) overlaps with systemic sclerosis(SSc), dermatomyositis/polymyositis, Sjogren's syndrome(SS), rheumatoid arthritis(RA), and other diseases, the lack of specific serological indicators and clinical manifestations can result in missed diagnosis and/or misdiagnosis, leading to life-threatening in severe cases. Early diagnosis and treatment of overlap syndrome can help alleviate the impact on patients' quality of life and improve the prognosis. This article reviews the research progress in this disorder and its management strategies. Although there is currently limited research on SLE related overlap syndrome, its clinical manifestations and immunological characteristics are strongly related to the overlapping diseases. Specific tests and examinations in time can facilitate the diagnosis and treatment of overlap syndrome. [ABSTRACT FROM AUTHOR]

Purpose: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is known as "overlap syndrome" (OS). Patients with OS are usually older than patients with OSA alone, suffer from more profound oxygen desaturation during the obstructive events often accompanied by sustained nocturnal hypoventilation. Although oxygen-enriched positive airway pressure (PAP) is the treatment of choice in these patients, this therapy is often poorly tolerated particularly by the elderly. The aim of this study was to assess the usefulness of nocturnal oxygen therapy via nasal high flow (NHF-OT) as a possible alternative to PAP in patients with OS. Methods: Patients > 65 years old with OS and nocturnal respiratory failure (time spent below SaO2 90% (T90) > 30%) had cardio-respiratory monitoring performed at baseline, during NHF-OT, or during conventional oxygen therapy (COT). Results: A total of 40 patients were enrolled in the study. NHF-OT significantly reduced the apnea–hypopnea index (AHI) in all patients compared to baseline and COT. The mean basal AHI was 25.4 ± 8.6. During COT and NHF-OT, the AHI was 19.4 ± 7 and 5.4 ± 4.6, respectively (P < 0.001) and 19 patients reached an AHI < 5 during NHF-OT. The mean nocturnal SaO2% was 86.2 ± 2.6 at baseline and at equivalent FiO2 it significantly increased to 91.8 ± 2.4 during COT and to 93.9 ± 2.5 during NHF-OT (P < 0.001). The T90% was 48.7 ± 20.1 at baseline, 16.8 ± 11.7 during COT, and 8.8 ± 8.0 during NHF-OT (P < 0.001). Conclusions: In elderly patients with OS, nocturnal treatment with NHF-OT significantly reduces obstructive episodes and improves oxygenation. As the treatment is generally well tolerated compared to PAP, NHF-OT may be a possible alternative therapy in this subgroup of patients. [ABSTRACT FROM AUTHOR]

The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), termed the overlap syndrome (OVS), is associated with adverse outcomes that may be reversed with treatment. However, diagnosis is limited by the apparent need for in-laboratory polysomnography (PSG). WatchPAT is a portable diagnostic device that is validated for the diagnosis of OSA that might represent an attractive tool for the diagnosis of OVS.Subjects with established COPD were recruited from a general population. Subjects underwent PSG and simultaneous recording with WatchPAT. Pulmonary function testing and questionnaires were also performed.A total of 36 subjects were recruited and valid data was obtained on 33 (age 63 ± 7, BMI 28 ± 7, 61% male, FEV1 56 ± 20% predicted). There was no significant difference in the apnea-hypopnea index (AHI) between PSG and WatchPAT (19 ± 20 versus 20 ± 15 events/h; mean difference 2(-2, 5) events/h; p = 0.381). The AHI was not significantly different in rapid eye movement (REM) and non-rapid eye movement (NREM) determined by PSG versus REM and NREM determined by WatchPAT. WatchPAT slightly overestimated total and REM sleep time, and sleep efficiency. The sensitivity of WatchPAT at an AHI cut-off of ≥5, ≥15, and ≥30 events/h for corresponding PSG AHI cut-offs was 95.8, 92.3, and 88.9, respectively; specificity was 55, 65.0, and 95.8, respectively.WatchPAT is able to determine OSA reliably in patients with COPD. The availability of this additional diagnostic modality may lead to improved detection of OVS, which may in turn lead to improved outcomes for a group of COPD patients at high risk of poor outcomes.

Abstract Background Immune checkpoint inhibitors can result in overlap syndrome comprised of myasthenia gravis, myositis and myocarditis. However, the mortality predictors have not been clearly delineated. Methods We examined the characteristics of 11 patients diagnosed with overlap syndrome at Cleveland Clinic. All the available clinical, diagnostic, biochemical and disease specific factors were examined. Clinical predictors of increased mortality were using student t‐test for parametric data and Wilcoxon‐signed rank testing for nonparametric data. Results Seven patients out of eleven patients were alive during the analysis. Our study did confirm that troponins were indicator of early demise. However, study showed that elevated creatinine, BUN, and decreased hemoglobin were also observed in patients who met early demise. Unlike previously published studies, elevated NT Pro‐BNP and reduced left ventricular ejection fraction were not a seen in this study. However, there were higher incidence of electrical abnormalities in deceased patients when compared to alive. Conclusion Our study is first to examine various clinical parameters of overlap syndrome that might be predictive of mortality. This study confirms troponin as possible predictor and adds elevated creatinine, BUN and reduced hemoglobin as possible early biomarkers in deceased patients. The analysis showed that reduced LVEF was not a seen in deceased patients.

Methods: In this observational study from October 2018 to August 2020, we included all the patients of MCTD and overlap syndromes. Alarcon–Segovia criteria was used as defining criteria for MCTD patients while the patients meeting diagnostic criteria for more than 1 of 6 classical autoimmune rheumatic diseases were selected in the overlap syndromes group. We compared their clinical features, laboratory parameters, and autoantibody profiles. MS Excel, STATA were used for statistical analysis, and comparison between the groups was done with t-test, Chi-square test, and Wilcoxon rank sum test. P < 0.05 was considered as statistically significant. Results: The study consisted of 60 consecutive patients (MCTD, n = 30 and overlap syndromes, n = 30) with higher female population in both groups (90% in MCTD and 84% in the overlap syndromes group) compared to males. The incidence of fever (83.3% vs. 46.6%), weight loss (60% vs. 26.6%), trigeminal neuralgia (76.6% vs. 13.3%), and myositis (63.3% vs. 20.0%) was significantly higher in MCTD than overlap syndromes whereas the incidence of cough (66.6% vs. 90.0%) and dry mouth (20.0% vs. 53.3%) was higher in overlap syndromes than MCTD (P < 0.05). Anti-U1 RNP antibodies were seen in all MCTD (100.0%) patients while anti-Scl 70 antibodies (60%) and anti-ribosomal-p-protein antibodies (13.3%) were seen in overlap syndromes. Conclusion: Fever and weight loss, trigeminal neuralgia, and myositis were more common in MCTD than overlap syndromes. Anti-U1 RNP antibodies seen in MCTD while Anti-Scl 70 antibodies and anti-ribosomal-P antibodies were commonly were seen in overlap syndromes.

Antimitochondrial antibody-positive primary biliary cholangitis (AMA-pos PBC) is an autoimmune disorder in which monoclonal antibodies are produced against epitopes in the mitochondrial membranes of biliary epithelial cells, resulting in progressive nonsuppurative biliary cholangitis. Up to 5% of patients lack these autoantibodies, termed antimitochondrial antibody-negative (AMA-neg) PBC. Although a somewhat new variant of AMA-pos PBC, it is not an overlapping syndrome. Few studies to date have described this phenomenon. An 87-year-old woman was referred to our clinic with elevated serum alkaline phosphatase (714 U/L). She reported fatigue but no other symptoms. A physical examination revealed a benign lesion and bilateral lower extremity swelling secondary to lymphedema. The serological profile was significant for a high antinuclear antibody titer (>1:2,560) with a centromere pattern and negative for antimitochondrial antibody (AMA). The hepatitis panel was negative for viruses A, B, and C. Her serum immunoglobulin G level was 871 mg/dL (normal,

Background and Aim: Sleep-disordered breathing (SDB) is an extremely common disorder with a high impact on morbidity and mortality. The purpose of this study was to compare overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) and to highlight and understand the differences between them. Material and Methods: The study was conducted retrospectively on 132 subjects selected by consecutive sampling from those attending our unit for suspected SDB. After clinical evaluation as well as functional and sleep investigations, the population was divided according to diagnosis in OS and OHS; then, the clinical parameters of two groups were compared with different statistical analysis. Results: The subjects with OHS were younger and reported higher rated daytime sleepiness (p = 0.005). In addition, they presented more nocturnal respiratory events (apnea-hypopnea index (AHI) 63.61 ± 22.79 events·h−1 vs. AHIOS 42.21 ± 22.91 events·h−1, p < 0.0001) at the sleep investigation as worse gas exchange during sleep leading to a higher percentage of nocturnal hypoxemia (p < 0.0001). In contrast, subjects with OS had more an impaired respiratory function. With regard to night-time ventilatory therapy, more subjects with OS were effectively treated with continuous positive airway pressure (CPAP) (p = 0.011), while more OHS were treated with auto-adjusting PAP (APAP) (14% vs. 1%, p = 0.008). Conclusions: The present study tried to establish a framework for OS and OHS because proper management of the two disorders would reduce their burden on healthcare.

Aim: to review the common risk factors and links in the pathogenesis of functional gastrointestinal disorders (FGID) to optimize therapy of patients with a combination of multiple FGID.Key points. FGID occurs in more than 40 % of people globally, mainly affecting the working-age population in young and middle-aged subjects. At the same time, more than 30 % of patients have a combination of 2 or more functional gastrointestinal (GI) disorders i.e. overlap syndrome. Common links in the pathogenesis of FGID include disorders of gut-brain interaction, visceral hypersensitivity, changes in intestinal microbiota, overproduction of proinflammatory cytokines, impaired epithelial permeability and motor activity of the gastrointestinal tract. The combination of FGID in various gastrointestinal segments is associated with more pronounced clinical symptoms (mutual burden syndrome). Common risk factors and pathogenetic links of the functional disorders enables reducing the number of prescribed medications when several FGIDs overlap in one patient, which also increases adherence to therapy. Treatment of FGID includes adjustment of risk factors and drug therapy. As a pathogenetically justified pharmacotherapy of overlap syndrome, Kolofort, highly diluted antibodies to TNF-α, histamine and brain-specific protein S-100, is of interest.Conclusion. Kolofort has demonstrated high efficacy and safety including among patients with overlap FGID enabling to consider it as the treatment of choice in these patients.

Abstract Background The peculiar presentation of overlap syndrome in children makes precise diagnosis difficult. Children with overlap syndrome may or may not have specific antibodies. We present the case of a 12-year-old girl diagnosed with overlap syndrome of systemic lupus erythematosus (SLE) and juvenile polymyositis (JPM) who tested positive for anti-OJ antibodies. Case presentation We describe the case of a 12-year-old girl diagnosed with SLE at the age of 7 and presented with fever with malar rash, periungual erythema, generalized weakness, and multiple joint pain at admission. The patient had persistent joint pain and weakness after intravenous methylprednisolone administration and complained of an inability to walk with a positive test for Gower's sign one week after admission, accompanied by elevated alanine aminotransferase (ALT) and creatine-phospho-kinase (CPK) levels. The results of nerve conduction velocity test were normal. Electromyography revealed abundant spontaneous activity and myopathic motor unit action potentials in the right deltoid, biceps, and iliopsoas, in addition to fibrillation and mild myopathic motor unit action potentials in the right rectus femoris muscle. Magnetic resonance imaging revealed diffusely increased signal intensities in the myofascial planes of the bilateral iliopsoas, gluteus, obturator, pectineus, and hamstring muscles. Anti-nuclear antibody, anti-RNP, and rheumatoid factor IgG tests were positive, and inflammatory myopathy autoantibodies revealed anti-OJ antibody positivity, which strongly indicated autoimmune myositis. High-resolution computed tomography of the lung revealed mild pericardial effusion without any evidence of interstitial lung disease. We initiated intravenous pulses of methylprednisolone treatment, followed by cyclosporine, mycophenolate mofetil, and oral steroids. Clinical improvement with a delayed, slowly reduced CPK level after the above treatment and she was discharged after the 18th day of hospitalization. Conclusion Overlap syndrome with inflammatory myositis can occur years later in pediatric SLE cases. We should be alert when patients with SLE develop a new presentation characterized by decreased SLE-specific autoantibody titers, positive anti-RNP antibodies, and elevated CPK. Treatment of the overlap syndrome of SLE and JPM is individualized, and the course differs between pediatric and adult patients.

Primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and ulcerative colitis (UC) are immune diseases of the digestive system. Some patients develop overlap syndrome, the presentation of two or more of the clinical, biochemical, immunological, and histological features of these conditions simultaneously or sequentially. The incidence of UC in PSC-AIH overlap syndrome is as high as 50%. In contrast, PSC-AIH overlap syndrome is rare in UC patients. However, because it has a low prevalence and has been studied in less detail, PSC is often misdiagnosed as primary biliary cholangitis (PBC) in its early stage. Herein, we reported a case of a 38-year-old male patient who presented to a clinician in 2014 with irregular bowel habits. A colonoscopy suggested UC. In 2016, the patient was found to have abnormal liver function and was diagnosed with PBC by pathology. He was treated with ursodeoxycholic acid (UDCA) but this had no effect on his liver function. Additional liver biopsies in 2018 indicated PBC-AIH overlap syndrome. The patient refused hormone therapy for personal reasons. Following UDCA monotherapy, his liver function remained abnormal. The patient was reexamined after repeated abnormal liver function tests and bowel symptoms. Systematic laboratory testing, imaging diagnosis, colonoscopy, liver biopsy, and various pathological examinations conducted in 2021 were used to diagnose the patient with PSC-AIH-UC overlap syndrome. He was treated with various drugs, including UDCA, methylprednisolone, mycophenolate mofetil, and mesalazine. His liver function improved significantly after treatment and follow-up is ongoing. Our case report highlights the need to raise awareness about rare and difficult-to-diagnose clinical disorders. [ABSTRACT FROM AUTHOR]

Because of some similarities in organ involvement, clinical manifestations, and histopathological features, IgG4-related disease (IgG4-RD) may occur concurrently with some clinicopathologic variants of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). An overlap syndrome of IgG4-RD and AAV has recently been proposed in clinical and/or histopathological studies, indicating that there may be some potential pathophysiological associations between the two disease entities; however, the mechanisms underlying these are incompletely understood. Here, we describe a rare case of a 63-year-old man with IgG4-related tubulointerstitial nephritis (IgG4-TIN) and microscopic polyangiitis-associated glomerulonephritis (MPA-GN) overlap syndrome. The clinical diagnosis of MPA was based on the 2022 American College of Rheumatology (ACR)/European League Against Rheumatology (EULAR) classification criteria. Remission induction therapy with intravenous methylprednisolone was initiated, followed by oral prednisone maintenance therapy with gradual tapering. The patient remained asymptomatic and his renal function was essentially normalized within 3.5 months of follow-up. The serum IgG4 levels decreased to 5 g/L. We also conducted a literature review to identify clinical findings, treatment options, and outcomes of patients with concurrent IgG4-RD and MPA and briefly discussed the potential pathophysiological association between IgG4-RD and MPA. Our findings enrich the database of this rare overlap syndrome and provide a basis for the diagnosis and early intervention in both diseases. These results provide some insights for clinicians to recognize and treat this overlap syndrome. Key Points • We report a unique case that enriches the database of this rare overlap syndrome and provides a basis for the outcome and early intervention in both diseases. •Several studies have suggested that IgG4-RD and MPA have a potential association, and we describe the pathophysiological mechanism of the overlap syndrome for the first time. • There have been no standardized diagnostic criteria for MPA for over 30 years; the 2022 ACR/EULAR classification criteria are expected to solve this problem. • We provide some clues for the diagnosis and treatment of this overlap syndrome based on the literature review. [ABSTRACT FROM AUTHOR]

Background: Overlap syndrome between primary biliary cholangitis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only few published cases so far in the literature. We highlight here the rarity of this condition and indicate the importance of its recognition. Case presentation: We report two cases showing the manifestations of both primary biliary cholangitis and primary sclerosing cholangitis in two Tunisian female patients aged 74 and 42 years, respectively. The first case is a woman who was initially diagnosed with decompensated cirrhosis. Magnetic resonance cholangiopancreatography showed multiple strictures of the common bile duct, and histological findings led to the diagnosis of primary biliary cholangitis/primary sclerosing cholangitis. She was successfully treated with ursodeoxycholic acid. The second case is a middle-aged woman, suffering from primary biliary cholangitis and who was treated with ursodeoxycholic acid. At her 12 month follow-up appointment, she presented with a partial clinical and biochemical response. Tests showed normal thyroid function, liver autoimmune tests for autoimmune hepatitis were negative, and celiac disease markers were also negative. The diagnosis of overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis was finally made on the results of magnetic resonance cholangiopancreatography that showed multiple strictures of the common as well as intrahepatic bile ducts. The patient was put on ursodeoxycholic acid at a higher dose. Conclusions: Our cases raise awareness for this rare condition and indicate the importance of recognizing a possible overlap syndrome, especially in patients with primary biliary cholangitis, to optimize treatment. We suggest considering the overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis when a patient presents with the diagnostic criteria of both diseases. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This is an extremely rare case that has not been presented or discussed in the literature to the best of our knowledge. The overlap of connective tissue disease is a challenge for physicians and patients, and it needs special care and regular clinical and laboratory follow‐up. This report describes a rare case of overlapping connective tissue diseases in a 42‐year‐old female with rheumatoid arthritis, Sjogren's syndrome, antiphospholipid syndrome, and dermatomyositis. The patient presented with a hyperpigmented erythematous rash, muscle weakness, and pain, highlighting the challenges of diagnosis and treatment that require regular clinical and laboratory follow‐up. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) leads to pulmonary and systemic involvement that could damage the cardiac autonomic modulation (CAM), increasing cardiovascular risks and mortality rates. The obstructive sleep apnea (OSA) syndrome is also associated to harmed CAM. However, it is not clear if the presence of OSA in COPD patients causes an additional loss on the autonomic nervous function. Objective: To compare the responses of CAM during the respiratory sinus arrhythmia maneuver (RSA‑M) between patients with OSA and COPD overlapped and COPD on isolation. Materials and Methods: Twenty‑four patients(COPD, n = 11; OSA‑COPD, n = 13) underwent pulmonary, cardiac function, and home sleep tests for diagnosis and staging of the disease. Heart rate (HR) and R-R intervals were collected during spontaneous breathing (SB) (sitting [10 min]) and the slow and deep breaths to trigger RSA‑M (sitting [4 min]). Results: Both groups showed impaired responses when SB and RSA‑M were compared. Both COPD and OSA‑COPD patients showed increased sympathetic modulation, observed through increased LF (low frequency), and LF/HF ratio (P < 0.05) and decreased HF (high frequency) (P < 0.05), an opposite pattern to that expected for RSA‑M. In addition, OSA‑COPD showed worse HR variability complexity response on RSA‑M (interaction effect, P < 0.05) and reduced spectral peak when contrasted with COPD alone (P < 0.05). Conclusions: The results suggest the presence of both COPD and OSA lead to a negative impact on the autonomic control of HR and deep‑breathing exercises. Future clinical trials that investigate the impact of breathing exercises on these autonomic indices should address the relevance of improving the autonomic balance in these patients. [ABSTRACT FROM AUTHOR]

Background and objective: The aim of this study was to elucidate the clinical and myopathological characteristics of patients with anti-signal recognition particle (SRP) positive immune-mediated necrotizing myopathy (IMNM) overlap Sjogren's syndrome (SS). Materials and methods: We retrospectively analyzed the data of anti-SRP positive IMNM patients admitted in the Neurology Department of Tongji Hospital between January 2011 to December 2020. Patients were divided into two groups: anti-SRP IMNM overlap SS group and anti-SRP IMNM control group. The clinical features, laboratory results, histological features, treatment, and prognosis were compared between the two groups. Results: A total of 30 patients with anti-SRP IMNM were included, including six anti-SRP IMNM overlap SS patients (two males, four females), with a median age of 39 years, and 24 anti-SRP IMNM patients (ten males, fourteen females), with a median age of 46 years. The anti-SRP IMNM overlap SS group had a lower prevalence of muscle atrophy (0 vs 50%, p = 0.019), and a higher prevalence of extramuscular manifestations, including cardiac abnormalities and ILD (Interstitial lung disease). CD4 + and CD68 + inflammatory infiltrations were significantly increased in anti-SRP IMNM overlap SS patients, with an increased presence of CD4 + cells in both necrotic(p = 0.023) and endomysial areas (p = 0.013), and more CD68 + cells (p = 0.016) infiltrated the endomysial area. Deposition of membrane attack complex (MAC) on sarcolemma (p = 0.013) was more commonly seen in the anti-SRP IMNM overlap SS group. Conclusion: Our data revealed that anti-SRP IMNM-SS overlap patients may present with milder muscular manifestation, but worse extramuscular manifestations compared to anti-SRP IMNM patients without SS. CD4 + and CD68 + inflammatory infiltrations and MAC deposition were remarkably increased in anti-SRP IMNM-SS overlap patients. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea syndrome (OSA) is increasingly reported in patients with chronic obstructive pulmonary disease (COPD). Our research aimed to analyze the clinical characteristics of patients with overlap syndrome (OS) and develop a nomogram for predicting OSA in patients with COPD. Methods: We retroactively collected data on 330 patients with COPD treated at Wuhan Union Hospital (Wuhan, China) from March 2017 to March 2022. Multivariate logistic regression was used to select predictors applied to develop a simple nomogram. The area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the value of the model. Results: A total of 330 consecutive patients with COPD were enrolled in this study, with 96 patients (29.1%) confirmed with OSA. Patients were randomly divided into the training group (70%, n=230) and the validation group (30%, n=100). Age [odds ratio (OR): 1.062, 1.003-1.124], type 2 diabetes (OR: 3.166, 1.263-7.939), neck circumference (NC) (OR: 1.370, 1.098-1,709), modified Medical Research Council (mMRC) dyspnea scale (OR: 0.503, 0.325-0.777), Sleep Apnea Clinical Score (SACS) (OR: 1.083, 1.004-1.168), and C-reactive protein (CRP) (OR: 0.977, 0.962-0.993) were identified as valuable predictors used for developing a nomogram. The prediction model performed good discrimination [AUC: 0.928, 95% confidence interval (CI): 0.873-0.984] and calibration in the validation group. The DCA showed excellent clinical practicability. Conclusion: We established a concise and practical nomogram that will benefit the advanced diagnosis of OSA in patients with COPD. [ABSTRACT FROM AUTHOR]

Introduction: Patients with overlap syndrome (OS), that is obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), are at increased risk of acute exacerbations related to COPD (AECOPD). We assessed the effect of CPAP compliance on AECOPD, symptoms and pulmonary function in OS patients. Methods: Consecutive OS patients underwent assessment at baseline and at 12 months under treatment with CPAP of: AECOPD and hospitalizations, COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) questionnaires, pulmonary function testing and 6‐min walking test (6MWT). Results: In total, 59 patients (54 males) with OS were followed for 12 months and divided post hoc according to CPAP compliance into: group A with good (≥4 h CPAP use/night, n = 29) and group B with poor (<4 h CPAP use/night, n = 30) CPAP compliance. At 12 months, group A showed improvements in FEV1 (p = 0.024), total lung capacity (p = 0.024), RV/TLC (p = 0.003), 6MWT (p < 0.001) and CAT (p < 0.001). COPD exacerbations decreased in patients with good CPAP compliance from baseline to 12 months (17 before vs. 5 after, p = 0.001), but not in those with poor compliance (15 before vs. 15 after, p = 1). At multivariate regression analysis, COPD exacerbations were associated with poor CPAP compliance (β = 0.362, 95% CI: 0.075–0.649, p = 0.015). Conclusions: When compared to poorly compliant patients, OS patients with good CPAP compliance had a lower number of AECOPD and showed improved lung function and COPD related symptoms. [ABSTRACT FROM AUTHOR]