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.

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.

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.

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.

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.

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.

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.

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.

Update on autoimmune hepatitis

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features,hyperglobulinemia (IgG),and the presence of circulating autoantibodies,as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years,a couple of new insights into the genetic aspects,clinical course and treatment of AIH have been reported,which will be the focus of this review. In particular,we concentrate on genome-wide microsatellite analysis,a novel mouse model of AIH,the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH,and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis

Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease （AILD） remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry （UPLC-MS）, differed between autoimmune hepatitis （AIH） and primary biliary cir- rhosis （PBC）, to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS： Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS： The partial least squares discrimination analysis model （R2y=0.991, Q2=0.943） was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS： The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

Anti-N-methyl-D-aspartate Receptor Encephalitis Associated with Peripheral Nerve Injury:A Case Report

A patient with Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis presented with quadriplegia and multiple peripheral neuropathy with axonal lesion,confirmed by electrophysiological examination.The muscle strength in the limbs of the patient gradually recovered almost completely,accompanied by the reversal of neuroelectrophysiological symptoms,and the improvement of clinical manifestations,including consciousness,respiration and cognitive function.It was revealed that the neuropathy in NMDAR encephalitis involved motor or sensorimotor nerves more than pure sensory nerves.No autoantibodies were detectable,in contrast to other anti-NMDAR overlapping syndromes.Although the underlying mechanism remains unclear,it may be associated with autoimmune generalization.In conclusion,when patients with NMDAR encephalitis present with severe limb paralysis,the possibility of peripheral nerve damage should be considered.

Clinical features of the overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis: retrospective study

PBC-AIH overlap syndrome is an autoimmune liver disease between AIH （autoimmunehepatitis） and PBC （primary biliary cirrhosis）. To investigate the characteristic of the PBC-AIH ovedap syndrome, we have conducted a retrospective study of 12 diagnosed ovedap syndrome patients and compared them with typical PBC and AIH on the basis of clinical, biochemical, serological and histopathological findings.

Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis Overlap Syndrome:A Review

Primary sclerosing cholangitis(PSC)and primary biliary cirrhosis(PBC)are slow progressive diseases which have been increasing in prevalence.The pathogeneses of PBC and PSC are incompletely understood but the underlying mechanisms appear to be fundamentally autoimmune in origin.Although PBC and PSC appear to be separate entities,overlap has been described.Diagnosis depends on a combination of serological markers,imaging,and pathological criteria.The mainstay of treatment has been ursodeoxycholic acid and in some cases of extrahepatic biliary obstruction and overlap disorder,endoscopic retrograde cholangiopancreatography has been useful.

A Case of Autoimmune Hepatitis and Primary Biliary Cirrhosis Overlap Syndrome Treated with Chinese Herbs

Some patients present with overlapping features between disorders within the spectrum of autoimmune liver diseases, i.e., autoimmune hepatitis （AIH）, primary biliary cirrhosis （PBC）, and primary sclerosing cholangitis （PSC）, and are commonly classified as having an ＂overlap syndrome＂. The pathophysiological mechanisms underlying AIH-PBC overlap remain unclear.^（1） Due to the lack of standardization and variations in the populations under study,

Efficacy of ursodeoxycholic acid alone or combined with immunosuppressant in primary biliray cirrhosis- autoimmune hepatitis overlap syndrome

Objective To evaluate the efficacy of ursodeoxycholic acid(UDCA)alone or combined with immunosuppressant in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome(PBC-AIH).Methods From January2001 to December 2014,41 patients with PBC-AIH were screened out from patients with autoimmune hepatitis(AIH)and retrospectively analyzed.According to

Retrospective Analysis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in 88 Chinese Patients

Background： Stevens-Johnson syndrome （SJS） and toxic epidennal necrolysis （TEN） are life-threatening diseases with high mortality rates. This study was designed to analyze the pathogenic factors, clinical manifestations, complications, treatment, and prognosis of SJS/TEN and to explore the differences between surviving and deceased patients. Methods： SJS/TEN patients admitted to Beijing Friendship Hospital from January 2006 to December 2015 were included in the study. Patients＇ data were retrospectively analyzed. Comparative studies were performed on the survival group and the deceased group, and Fisher＇s exact probability test was used for statistical analysis. Results： Among the 88 patients included, 40 （45.5%） were male with a mean age of 45 - 18 years. Forty-eight （54.5%） had SJS, 34 （38.6%） had SJS/TEN, and 6 （6.8%） had TEN. Fifty-three （60.2%） cases were caused by medications, mainly antibiotics （n = 24） followed by traditional Chinese medicines 97 - 7）. Forty-two cases （47.7%） developed visceral damage. Eighty-two patients improved or recovered and were discharged from hospital, and six patients died. Comparative studies on the survival group and the deceased group showed that the presence of malignant tumor （Z2 = 27.969, P 〈 0.001）, connective tissue diseases （x^2 - 9.187, P = 0.002）, previous abnormal liver/kidney functions （x^2 = 6.006, P = 0.014）, heart rate 〉100 times/rain （x^2 = 6.347, P = 0.012）, detached skin area 〉20% （x^2 = 5.594, P = 0.018）, concurrent mucosal involvement at the mouth, eyes, and external genitals （Z2 = 4.945, P = 0.026）, subsequent accompanying liver/kidney damage （x^ = 11.839, P = 0.001, and x^2 = 36.302, P 〈 0.00 l, respectively）, and SCORTEN score 〉2 （x^2 = 37.148, P 〈 0.001 ） increased the risk of death. Conclusions： SJS/TEN is mainly caused by medications, and nearly half of patients develop visceral damage. Multiple factors increase the mortality risk.

A ＂Triple Trouble＂ Case of Facioscapulohumeral Muscular Dystrophy Accompanied by Peripheral Neuropathy and Myoclonic Epilepsy

Background： Facioscapulohumeral muscular dystrophy （FSHD） is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a ＂complex disease plus＂ patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. Methods： Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification （MLPA）, whole exome sequencing （WES）, and targeted methylation sequencing. Results： The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient＇s mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES. Conclusions： The present study described a ＂tripe trouble＂ with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.