Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Predictors of survival in autoimmune liver disease overlap syndromes

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.

Irritable bowel syndrome:Epidemiology,overlap disorders,pathophysiology and treatment

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disease with a significant impact on patients’ quality of life and a high socioeconomic burden. And the understanding of IBS has changed since the release of the Rome Ⅳ diagnosis in 2016. With the upcoming Rome Ⅴ revision, it is necessary to review the results of IBS research in recent years. In this review of IBS, we can highlight future concerns by reviewing the results of IBS research on epidemiology, overlap disorders, pathophysiology, and treatment over the past decade and summarizing the latest research.

Feasibility of Tiotropium Bromide Treatment in Patients with Asthma-COPD Overlap Syndrome and its Effect on Lung Function

Objective:To explore the feasibility of tiotropium bromide therapy and its effect on the lung function of patients with asthma-COPD overlap syndrome(ACOS).Method:The 58 subjects selected in this study were all ACOS patients admitted to our hospital(Hohhot First Hospital)from October 2020 to October 2022.They were grouped according to the random number table method and divided into a control group(29 cases)and an observation group(29 cases).The control group received routine treatment plus salmeterol-fluticasone powder inhalation treatment,and the observation group received tiotropium bromide treatment.The relevant indicators of the two groups were compared.Results:The total clinical effective rate of the observation group was significantly higher than that of the control group.Besides,the forced vital capacity(FVC),forced expiratory volume in 1 second(FEV1)levels,and ACT scores of the two groups increased after treatment,with the observation group having better results than the control group.The residual volume-total lung capacity ratio(RV/TLC),acute exacerbation frequency,and CAT scores all decreased,with the observation group showing smaller values than the control group.The difference between the results of both groups were significant(P<0.05)Conclusion:Tiotropium bromide has a significant clinical effect in the treatment of ACOS patients and can effectively improve the lung function of patients.

Performance of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome

AIM To investigate the performance of transient elastography(TE) for diagnosis of fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis(AIHPBC) overlap syndrome.METHODS A total of 70 patients with biopsy-proven AIH-PBC overlap syndrome were included. Spearman correlation test was used to analyze the correlation of liver stiffness measurement(LSM) and fibrosis stage. Independent samples Student's t-test or one-way analysis of variance was used to compare quantitative variables. Receiver operating characteristics(ROC) curve was used to calculate the optimal cut-off values of LSM for predicting individual fibrosis stages. A comparison on the diagnostic accuracy for severe fibrosis was made between LSM and other serological scores.RESULTS Patients with AIH-PBC overlap syndrome had higher median LSM than healthy controls(11.3 ± 6.4 k Pa vs 4.3 ± 1.4 k Pa, P < 0.01). LSM was significantly correlated with fibrosis stage(r = 0.756, P < 0.01). LSM values increased gradually with an increased fibrosis stage. The areas under the ROC curves of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.837(95%CI: 0.729-0.914), 0.910(0.817-0.965), and 0.966(0.893-0.995), respectively. The optimal cut-off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.55, 10.50, and 14.45 k Pa, respectively. LSM was significantly superior to fibrosis-4, glutaglumyl-transferase/platelet ratio, and aspartate aminotransferase-to-platelet ratio index scores in detecting severe fibrosis(F ≥ 3)(0.910 vs 0.715, P < 0.01; 0.910 vs 0.649, P < 0.01; 0.910 vs 0.616, P < 0.01, respectively).CONCLUSION TE can accurately detect hepatic fibrosis as a noninvasive method in patients with AIH-PBC overlap syndrome.

An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood

We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis （AIH） and systemic lupus erythematosus （SLE）. The patient presented with jaundice, hepatosplenomegaly, malaise, polyarthralgia, arthritis and butterfly rash on the face. Laboratory tests revealed severe liver dysfunction, Coombs positive hemolytic anemia and a positive ANA/ anti-dsDNA test. Renal biopsy showed class IIA kidney disease, while liver biopsy showed chronic hepatitis with severe inflammatory activity. The patient satisfied the international criteria for both SLE and AIH. Clinical symptoms and laboratory findings of SLE improved with high dose treatment with corticosteroids and azathioprine, however, remission of the liver disease could not be achieved. Repeat biopsy of the liver after three years of therapy revealed ongoing chronic hepatitis with high level of inflammatory activity. The present case indicates that children with liver dysfunction and SLE should be investigated for AIH. There is much diagnostic and therapeutic dilemma in patients with AIH-SLE overlap syndrome.

Direct acting antiviral therapy is curative for chronic hepatitis C/autoimmune hepatitis overlap syndrome

Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting antiviral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology.

Overlap syndrome consisting of PSC-AIH with concomitant presence of a membranous glomerulonephritis and ulcerative colitis

The association of primary sclerosing cholangitis(PSC)and autoimmune hepatitis(AIH)is known as an overlap syndrome(OS).OS can also be described in the setting of concomitant presence of AIH and PSC.These diseases can in some cases be associated with ulcerative colitis.In this case report we describe,to our knowledge,the first case in the literature of a young Caucasian male suffering from ulcerative colitis and an overlap syndrome consisting of an association betweenPSC-AIH,with the concomitant presence of a membranous glomerulonephritis.

Primary pulmonary plasmacytoma accompanied by overlap syndrome:A case report and review of the literature

BACKGROUND Extramedullary plasmacytoma(EMP)is a rare kind of soft tissue plasma cell neoplasm without bone marrow involvement;this type of plasma cell neoplasm involves a lack of other systemic characteristics of multiple myeloma.Primary pulmonary plasmacytoma(PPP),with no specific clinical manifestations,is an exceedingly rare type of EMP.Because of its complexity,PPP is often difficult to diagnose,and there is no report in the literature on cases accompanied by overlap syndrome(OS).CASE SUMMARY A 61-year-old woman without a familial lung cancer history was admitted to our hospital in 2018,for intermittent cough,expectoration,and a stuffy feeling in the chest for 50 years;these symptoms appeared intermittently,especially occurred after being cold,and had been aggravated for the last 10 d.She was diagnosed with pulmonary fibrosis and emphysema,bronchiectasis,OS,and autoimmune hepatic cirrhosis in 2017.A pulmonary examination revealed rough breath sounds in both lungs;other physical examinations found no obvious abnormalities.A routine laboratory work-up showed decreased haemoglobin,increased ESR,and abnormal GGT,ALT,Ig G,γ-globulin,κ-light chain,λ-light chain,rheumatoid factor,and autoimmune antibodies.Emission computed tomography demonstrated abnormally concentrated 99 m Tc-MDP.Chest computed tomography revealed a soft tissue mass in the middle and lower lobes of the right lung.After right middle and inferior lobe resection with complete mediastinal lymph node dissection,immunohistochemical analysis revealed an isolated pulmonary plasmacytoma.The patient received chemotherapy for more than 1.5 years and remains in good general condition.CONCLUSION PPP is a type of EMP,and we report an exceedingly rare presentation of PPP accompanied by OS.

Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report

BACKGROUND Systemic lupus erythematosus(SLE)and antineutrophil cytoplasmic antibodyassociated vasculitis(AAV)are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies.Their overlap constitutes a rare rheumatologic disease.To date,only dozens of such cases with biopsyproven glomerulonephritis have been reported worldwide typically in women of childbearing age.Here,we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life.CASE SUMMARY A 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years.As his symptoms were not completely relieved,he visited our hospital for further treatment.Laboratory examinations revealed kidney dysfunction,severe anaemia,hypocomplementemia,glomerular proteinuria,and microscopic haematuria.Antinuclear antibodies,as well as anti-dsDNA antibodies,were positive.Computed tomography of the chest showed right pleural effusion.Renal biopsy was performed,and histology suggested crescentic glomerulonephritis,pauci-immune type.After treatment with plasmapheresis,glucocorticoid,and cyclophosphamide,the disease was in remission,and the patient remained in a stable condition for over 3 years post-hospital discharge.CONCLUSION Due to its complexity and rarity,SLE and AAV overlap syndrome is easily misdiagnosed.An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.

Therapeutic Effect Observation of Tiotropium Bromide in the Treatment of Overlap Syndrome

Objective:To study the M receptor blocker on inhalation in patients with overlap syndrome(chronic obstructive pulmonary disease and Obstructive sleep apnea syndrome)curative effect analysis.Methods:25 patients with overlap syndrome as the experimental group,chronic obstructive pulmonary disease patients(30)as control group,patients with overlap syndrome use inhaled tiotropium powder treat 30 days,to observe the changes of pulmonary function,polysomnography,and other indicators after treatment.Results:Overlap syndrome were treated by tiotropium bromide inhalation powder,has improved the pulmonary function,the sleep apnea index and lowest nocturnal oxygen saturation after treatment.Conclusion:tiotropium bromide has a preferable effective in treatment of overlap syndrome,COPD and OSAHS are interacting with each other.

Autoimmune Hepatitis-Primary Biliary Cirrhosis: Overlap Syndrome Concomitant with Unexpected Myasthenia and Thymoma

The myasthenia gravis is an autoimmune disease which can be associated frequently with a thymoma and also with autoimmune pathologies. We report the case of a 64-year-old man affected an overlap syndrome corresponding to the association of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). He also presented concomitant myasthenia gravis and thymoma. The physical examination notes only a disturbed voice. The liver tests showed: alkaline phosphatase 600 U/l, alanine aminotransferase 1280 U/l, and aspartate aminotransferase 985 U/l. Viral serologies of hepatitis were all negative, as well as antinuclear, antimitochondrial and antismooth muscle antibodies. The diagnosis of an overlap syndrome was posed according to the biological and hepatic histhological results. An associated myasthenia was confirmed by the results of the EMG and the positivity of the anti-acetylcholine receptor antibody. A chest CT revealed a thymoma. The treatment consisted of ursodeoxycholic acid, prednisone, azathioprine and pyridostigmine. And the patient improved his voice and the liver function. Thymectomy was practiced without incidents.

Asthma-chronic obstructive pulmonary disease overlap syndrome: A diagnostic puzzle for the clinicians

Although asthma and chronic obstructive pulmonary disease(COPD) are distinct airway diseases characterized by chronic inflammation, in some cases distinguishing between them is puzzling. For example, chronic smoking leads asthmatic inflammation to a differentiated pattern resembling the COPD inflammation, and in some cases to fixed obstruction as in COPD, and on the other hand, few COPD patients may present with airway reversibility. ACOS is the condition sharing features encountered both in asthma and COPD. Asthma-COPD overlap syndrome(ACOS) represents a diagnostic challenge in the clinical practice, since there is lack of specific indicators to distinguish it from asthma or COPD, and moreover, genetic risk factors, underlying pathology and molecular pathways, clinical characteristics, therapeutic interventions, response to treatment and prognosis are poorly described. The management of ACOS is recommended to be individualized and should target on the maximum effectiveness with the least side effects. Combination therapy with ICS/LABA or LAMA, or newly developed specific anti-eosinophil therapies and treatments specifically targeting neutrophils might be of relevance in the management of ACOS, but studies are needed in order to assess the response and prognosis. Based on the current knowledge about ACOS thus far, it would be recommended that we approached chronic obstructive airway disease rather by describing than by classifying the disease; this would allow us to have a picture that better describes the disease and to implement an individualized therapeutic approach, according to the custom phenotype. Nevertheless, more studies are needed in order to clarify several important issues with regard to ACOS, such as the genetic risk factors for developing ACOS, the links between genotype and phenotype, the molecular pathways and underlying mechanisms of ACOS, the identification of possible specific biomarkers for diagnosis and targeted treatment, the optimal therapeutic interventions, and finally, the prognosis of ACOS.

Management of Overlap Syndrome between Functional Dyspepsia and Irritable Bowel Syndrome by Western and Traditional Chinese Medicine

The overlap syndrome of functional dyspepsia and irritable bowel syndrome (FD-IBS) is very common and difficult to treat. There are many risk factors of FD-IBS. Mental illness of FD-IBS patients is more serious. Functional dyspepsia and irritable bowel syndrome have some similarities in the aspects of pathophysiology, pathogenesis, and treatment. We should pay attention to two aspects of the treatment of overlap syndrome, one is simplifying medications, the other is using gastrointestinal motility drug with bidirectional regulative function when necessary. Traditional Chinese medicine in this respect shows some advantages. This review addresses the epidemiology, risk factors, clinical features, pathogenesis and management of FD-IBS.

Druggable monogenic immune defects hidden in diverse medical specialties:Focus on overlap syndromes

In the last two decades two new paradigms changed our way of perceiving primary immunodeficiencies:An increasing number of immune defects are more associated with inflammatory or autoimmune features rather than with infections.Some primary immune defects are due to hyperactive pathways that can be targeted by specific inhibitors,providing innovative precision treatments that can change the natural history of diseases.In this article we review some of these“druggable”inborn errors of immunity and describe how they can be suspected and diagnosed in diverse pediatric and adult medicine specialties.Since the availability of precision treatments can dramatically impact the course of these diseases,preventing the development of organ damage,it is crucial to widen the awareness of these conditions and to provide practical hints for a prompt detection and cure.

Differential Diagnosis and Association of Acquired Immunodeficiency Syndrome and Systemic Erythematous Lupus: A Brief Review

Acquired immunodeficiency syndrome and lupus erythematosus are multisystem diseases that can affect several organs and systems at different stages of disease evolution. Both diseases share common clinical manifestations, which may lead to diagnostic difficulties, especially at the onset of the disease. Another additional challenge is when there is an association of the two pathologies. The objective of this brief review is to describe the clinical manifestations of the diseases and to make considerations regarding the moment of onset of symptoms. Knowledge of these common manifestations and their peculiarities may alert clinicians to possible diagnoses and avoid errors in the evaluation and conduction of these patients.

抗核抗体谱对AIH-PBC OS及单纯AIH患者激素应答的影响

目的探讨抗核抗体谱(ANAs)对自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征(AIH-PBC OS)及单纯AIH患者半年内激素应答的影响。方法回顾性分析2018年1月-2021年12月兰州大学第一医院收治的77例自身免疫性肝病(AILD)患者的资料,其中AIH-PBC OS组46例,单纯AIH组31例。均经肝穿刺活检组织病理检查确诊,并行糖皮质激素治疗。比较两组患者的一般临床特征、肝穿刺相关指标、自身抗体及免疫球蛋白指标,以及患者使用糖皮质激素初始及6个月内复查的生化及免疫球蛋白指标,根据谷草转氨酶(AST)、谷丙转氨酶(ALT)及免疫球蛋白G(IgG)水平评估治疗6个月内的激素应答情况,采用多因素有序logistic分析ANAs对两组患者激素应答结果的影响。结果ANAs阳性及阴性AILD患者中,AIH-PBC OS及单纯AIH患者占比均无统计学差异(55.6%vs.44.4%,65.6%vs.34.4%,P>0.05)。46例AIH-PBC OS患者中,ANAs阳性组25例,ANAs阴性组21例。ANAs阳性组半年内激素完全应答率低于ANAs阴性组(44.0%vs.76.2%),而激素不应答率高于ANAs阴性组(20.0%vs.0),差异有统计学意义(P<0.05)。31例单纯AIH患者中,ANAs阳性组20例,ANAs阴性组11例。两组患者半年内激素应答结果差异无统计学意义(P>0.05)。多因素有序logistic分析结果显示,AIHPBC OS患者中,ANAs阳性者半年内激素不应答的可能性较大,差异有统计学意义(P<0.05)。而单纯AIH患者中ANAs类型对激素应答结果无明显影响(P>0.05)。结论在AIH-PBC OS患者中,ANAs阳性者半年内激素应答结果欠佳;在单纯AIH患者中,ANAs对激素应答结果无明显影响。

糠酸氟替卡松/乌美溴铵/维兰特罗三联疗法与传统ICS/LAMA疗法对ACO患者的临床疗效差异分析

目的探讨糠酸氟替卡松/乌美溴铵/维兰特罗(FF/UMEC/VI)三联疗法对哮喘-慢性阻塞性肺疾病重叠综合征(ACO)患者的临床疗效及与吸入型糖皮质激素(ICS)/长效抗胆碱能拮抗剂(LAMA)联合疗法的差异性。方法纳入2019年6月至2022年6月呼吸与危重症医学科收治的90例ACO患者,随机分为研究组与对照组,各45例。对照组患者予以ICS/LAMA治疗,研究组患者予以FF/UMEC/VI三联疗法治疗,治疗12周后比较两组患者用药前后肺功能指标变化、症状改善情况及疗效评价。结果治疗前研究组与对照组患者基础临床资料及各项肺功能指标差异无统计学意义(P>0.05)。治疗12周后研究组患者各项肺功能指标及血气分析指标较治疗前均显著改善(P<0.05)。不同方案治疗12周后,研究组患者各项肺功能改善程度均高于对照组患者(P<0.05)。治疗12周后研究组患者症状改善指标及治疗有效率均高于对照组患者(P<0.05)。结论FF/UMEC/VI三联疗法对于ACO患者具有显著治疗效果,能够改善患者肺功能,缓解患者临床症状,具有较为广阔的应用前景。

基于NHANES数据库低氧重叠综合征与心血管病的关联性研究

目的探讨阻塞性睡眠呼吸暂停综合征(Obstructive sleep apnea,OSA)、慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)及重叠综合征(overlap syndrome,OS)与心血管疾病的相关性。方法选取2005年~2008年美国国家健康和营养调查(National health and nutrition examination survey,NHANES)数据,共7716名参与者纳入本研究。按照是否存在OSA、COPD分为4组:无OSA及COPD组(n=3072)、单纯OSA组(n=4062)、单纯COPD组(n=180)、OS组(n=402)。本研究采用多因素logistic回归以探究OSA、COPD及OS与多种心血管疾病的关联。同时探究OSA、COPD和OS与年龄、性别、肥胖等心血管危险因素在心血管疾病中的关联性。结果相较于无OSA及COPD组,OS组心肌梗死(OR=2.85,95%CI=1.94~4.21)、充血性心力衰竭(OR=4.32,95%CI=2.73~6.84)、心绞痛(OR=3.07,95%CI=1.92~4.91)、卒中(OR=2.52,95%CI=1.61~3.97)、冠心病(OR=3.1,95%CI=2.22~4.31)及总体心血管疾病(OR=3.43,95%CI=2.54~4.63)的风险增加显著相关。单纯OSA症状人群中卒中发生率为无OSA及COPD组的1.46倍(OR=1.46,95%CI=1.07~1.99),充血性心力衰竭(OR=3.27,95%CI=1.77~6.07)、冠心病(OR=1.68,95%CI=1.03~2.73)和总体心血管疾病(OR=1.93,95%CI=1.25~3.00)的风险也显著升高。未观察到单纯OSA症状与心血管疾病的风险增加的相关性。OSA、COPD及重叠综合征与总体心血管疾病、冠心病和心肌梗死的关联在各亚组人群中稳定。结论OSA-COPD综合征与心肌梗死、充血性心力衰竭、心绞痛、卒中、冠心病及总体心血管疾病的发生风险增高存在显著相关性。监测及控制OSA-COPD重叠综合征对心血管疾病的预防有着重要意义。

异丙托溴铵联合糖皮质激素治疗哮喘-慢阻肺重叠综合征患者的效果

目的:探讨异丙托溴铵联合糖皮质激素治疗哮喘-慢阻肺重叠综合征(ACOS)患者的效果。方法:选择2022年1月—2023年6月泰兴市中医院呼吸科接诊的84例ACOS患者作为研究对象,按照随机数表法将其分为对照组与观察组,各42例。对照组给予糖皮质激素治疗,观察组给予异丙托溴铵联合糖皮质激素治疗。比较两组肺功能、膈肌功能、临床效果及安全性。结果:观察组治疗后用力肺活量(FVC)、第1秒用力呼气容积(FEV_(1))、FEV_(1)/FVC%均高于对照组,差异有统计学意义(P<0.05);观察组治疗后膈肌增分数、膈肌活动度均高于对照组,差异有统计学意义(P<0.05);观察组治疗总有效率为97.62%,高于对照组的88.10%,差异有统计学意义(P<0.05);两组治疗过程中均未出现不良反应情况。结论:异丙托溴铵联合糖皮质激素可改善ACOS患者肺功能、膈肌功能,提升临床治疗效果,且安全性较好。