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Paraneoplastic Anti-Tif1-gamma Autoantibody-positive dermatomyositis as Clinical Presentation of Hepatocellular Carcinoma Recurrence

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Journal of Clinical and Translational Hepatology 2023年第1期11卷 253-259页

作者： Marco Ferronato Claudine Lalanne Chiara Quarneti Michele Cevolani Chiara Ricci Alessandro Granito Luigi Muratori Marco Lenzi Division of Internal Medicine and Immunorheumatology IRCCS Azienda Ospedaliero-Universitaria di BolognaBolognaItaly Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System University of BolognaBolognaItaly Department of Medical and Surgical Sciences University of BolognaBolognaItaly Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIRCCS Azienda Ospedaliero-Universitaria di BolognaBolognaItaly

Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue,myalgia,and typical skin rash.His medical history was notable for hepatitis C-related cirrhosis,successful treatment with direct-acting antiviral agents,and previously efficacious treatment of HCC.Laboratory testing showed significant rhabdomyolysis with antiTIF1-γantibodies at high titer,and DM was diagnosed.After a careful diagnostic workup,HCC recurrence was diagnosed.After first-line corticosteroid treatment,azathioprine and intravenous immunoglobulin treatments were administered;unfortunately,he mounted only partial response.Owing to the compromised performance status,no HCC treatment was feasible,and,according to international guidelines,he received only best supportive care.Here,we discuss the diagnostic,prognostic,and pathogenic roles of anti-TIF1-γantibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients.Considering the TIF1 gene family’s established role in oncogenesis,we also review the role of TIF1-γas a tumor-related neoantigen,leading to the development of clinically overt antiTIF1-γantibodies-positive DM.

关键词： dermatomyositis Anti-transcriptional intermediary factor-1 gamma(tif1-γ)antibodies Hepatocellular carcinoma Paraneoplastic syndrome

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Pneumocystis jiroveci pneumonia after total hip arthroplasty in a dermatomyositis patient:A case report

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World Journal of Clinical Cases 2022年第10期10卷 3313-3320页

作者： Mao Hong Zi-Yu Zhang Xiao-Wei Sun Wei-Guo Wang Qi-Dong Zhang Wan-Shou Guo Beijing University of Chinese Medicine Beijing 100029China Department of Orthopaedic Surgery Beijing Key Lab Immune-Mediated Inflammatory DiseasesChina-Japan Friendship HospitalBeijing 100029China Graduate School of Peking Union Medical College Chinese Academy of Medical SciencesBeijing 100029China

BACKGROUND Pneumocystis jiroveci pneumonia(PJP)is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive therapy.In non-human immunodeficiency virus-infected patients,the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive treatments.The management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special care.CASE SUMMARY We report a case of PJP in the perioperative period.A 61-year-old woman with a history of anti-melanoma differentiation-associated gene 5(MDA5)-positive dermatomyositis and interstitial pneumonia was administered with long-term oral methylprednisolone and cyclosporine.The patient underwent right total hip arthroplasty in the orthopaedic department for bilateral osteonecrosis of the femoral head.She was given intravenous drip hydrocortisone before anesthesia and on the first day after surgery and resumed oral methylprednisolone on the second postoperative day.On the fifth day after surgery,the patient suddenly developed dyspnea.The computed tomography scan showed diffuse grid shadows and ground glass shadows in both lungs.Polymerase chain reaction testing of bronchoalveolar lavage fluid was positive for Pneumocystis jiroveci.The patient was eventually diagnosed with PJP and was administered with oral trimethoprim-sulfamethoxazole.At the 6-mo review,there was no recurrence or progression.CONCLUSION Continued perioperative glucocorticoid use in patients with anti-MDA5-positive dermatomyositis may increase the risk of PJP.

关键词： Pneumocystis jiroveci pneumonia Glucocorticoids Perioperative period dermatomyositis Hypothalamic-pituitary-adrenal axis Case report

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Treatment of gastric cancer with dermatomyositis as the initial symptom:Two case reports and review of literature

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World Journal of Clinical Cases 2022年第27期10卷 9727-9733页

作者： Xiang-Fei Sun Xiao-Dong Gao Kun-Tang Shen Department of General Surgery Zhongshan HospitalFudan University School of MedicineShanghai 200032China

BACKGROUND dermatomyositis(DM) is a rare autoimmune disease involving the connective tissue.The association between DM and gastric cancer remains unclear.Patients with DM have an increased risk of cancer and higher mortality.It requires immunosuppressive therapy,heightened surveillance,and immunologic response to internal malignancy.CASE SUMMARY Two cases of gastric cancer with DM as the first symptom in Zhongshan Hospital,Fudan University(Shanghai,China) were reported.Two patients had a typical skin rash.The rash in the first patient involved mainly bilateral upper limbs and neck,while the second patient manifested rash associated mainly with the face,neck,and back.Both manifested muscle weakness in the extremities and elevated serum creatine kinase.Radical resection of the tumor dramatically improved DMrelated symptoms in the two patients.The literature review showed that gastric cancer is more commonly associated with DM in middle-aged and older male populations.CONCLUSION The findings suggest the need for comprehensive screening for malignant tumors in patients with DM refractory to long-term pharmacotherapy or hormone manipulation.

关键词： Gastric cancer dermatomyositis Treatment Literature review Rash Case report

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α2,3-Sialylation with Fucosylation Associated with More Severe Anti-MDA5 Positive dermatomyositis Induced by Rapidly Progressive Interstitial Lung Disease

Phenomics

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Phenomics 2023年第5期3卷 457-468页

作者： Rongrong Zhang Li Guo Jichen Sha Shuwai Chang Jiangfeng Zhao Kaiwen Wang Jiucun Wang Jianxin Gu Jing Liu Shifang Ren NHC Key Laboratory of Glycoconjugates Research Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesFudan UniversityShanghai 200032China Zhangjiang Fudan International Innovation Center Human Phenome InstituteFudan UniversityShanghai 200032China Department of Rheumatology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200032China State Key Laboratory of Genetic Engineering School of Life ScienceFudan UniversityShanghai 200032China

dermatomyositis(DM)is a heterogeneous autoimmune disease associated with numerous myositis specific antibodies(MSAs)in which DM with anti-melanoma differentiation-associated gene 5-positive(MDA5+DM)is a unique subtype of DM with higher risk of developing varying degrees of Interstitial lung disease(ILD).Glycosylation is a complex posttranslational modification of proteins associated with many autoimmune diseases.However,the association of total plasma N-glycome(TPNG)and DM,especially MDA5+DM,is still unknown.TPNG of 94 DM patients and 168 controls were analyzed by mass spectrometry with in-house reliable quantitative method called Bionic Glycome method.Logistic regression with age and sex adjusted was used to reveal the aberrant glycosylation of DM and the association of TPNG and MDA5+DM with or without rapidly progressive ILD(RPILD).The elastic net model was used to evaluate performance of glycans in distinguishing RPLID from non-RPILD,and survival analysis was analyzed with N-glycoslyation score by Kaplan-Meier survival analysis.It was found that the plasma protein N-glycome in DM showed higher fucosylation and bisection,lower sialylation(α2,3-notα2,6-linked)and galactosylation than controls.In MDA5+DM,more severe disease condition was associated with decreased sialylation(specificallyα2,3-sialylation with fucosylation)while accompanying elevated H6N5S3 and H5N4FSx,decreased galactosylation and increased fucosylation and the complexity of N-glycans.Moreover,glycosylation traits have better discrimination ability to distinguish RPILD from non-RPILD with AUC 0.922 than clinical features and is MDA5-independent.Survival advantage accrued to MDA5+DM with lower N-glycosylation score(p=3e-04).Our study reveals the aberrant glycosylation of DM for the first time and indicated that glycosylation is associated with disease severity caused by ILD in MDA5+DM,which might be considered as the potential biomarker for early diagnosis of RPILD and survival evaluation of MDA5+DM.

关键词： dermatomyositis Anti-melanoma differentiation-associated gene 5-positive Interstitial lung disease Glycosylation Matrix assisted laser desorption/ionization time of flight mass spectrometry

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High-throughput transcriptomic profiling of mRNAs and lncRNAs in the dermatomyositis muscle by RNA sequencing

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Rheumatology & Autoimmunity 2023年第3期3卷 166-178页

作者： Ke Li Yubao Ma Shanchun Zhang Rui Ban Qiang Shi Department of Neurology The Second Medical CenterChinese PLA General HospitalBeijingChina Department of National Clinical Research Center of Geriatrics Disease Chinese PLA General HospitalBeijingChina Department of Neurology The First Medical CenterChinese PLA General HospitalBeijingChina Department of Neurology The First Affiliated Hospital of Tsinghua UniversityBeijingChina

Background:dermatomyositis(DM)is an idiopathic inflammatory myopathy(IIM).In this study,we investigated the mRNAs and long noncoding RNAs(lncRNAs)in muscle biopsy specimens that are differentially expressed among patients with DM,patients with other IIM,and healthy controls(HCs).Methods:In total,three patients with DM,10 patients with other IIM,and three HCs were included.Muscle biopsy specimens were collected for RNA-sequencing.Gene ontology and pathway analyses were employed to characterize the biological processes and signaling pathways.Results:Compared with HCs,372 differentially expressed mRNAs were identified within the DM group,including 275 upregulated and 97 downregulated ones.Moreover,692 differentially expressed lncRNAs were identified in the DM group compared with HCs,of which 407 were upregulated and 285 were downregulated.Bioinformatic analysis indicated that the type-Ⅰ interferon signaling pathway and biological processes of innate immunity were significantly influenced by the differentially expressed mRNAs.Notably,11 of the top 20 upregulated mRNAs were involved in the type-Ⅰ interferon signaling pathway.Reverse transcription polymerase chain reaction analysis verified the RNA-sequencing data.Target gene prediction analysis suggested that the lncRNA NONHSAG043573.2 potentially targeting transporter associated with antigen processing 1,a key regulator of interferon signaling genes,might play an important role in the pathogenesis of DM.Conclusions:Our study assessed the transcriptomic profiles of differentially expressed mRNAs and lncRNAs in the DM muscle tissue and revealed that the upregulated mRNAs are significantly involved in the innate immune response and the type-Ⅰ interferon signaling pathway,which might play important roles in the pathogenesis of DM.

关键词： dermatomyositis innate immune ISG15 lncRNA RNA-sequencing transporter associated with antigen processing 1(TAP1) type-Ⅰinterferon

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Treatment of refractory anti-melanoma differentiation-associated gene 5 anbibody-positive dermatomyositis complicated by rapidly progressing interstitial pulmonary disease:Two case reports

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World Journal of Clinical Cases 2023年第22期11卷 5351-5357页

作者： Qiao-Hong Wang Li-Heng Chen Department of Rheumatology Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310009Zhejiang ProvinceChina Department of Endocrinology Fourth Affiliated HospitalCollege of MedicineZhejiang UniversityYiwu 322000Zhejiang ProvinceChina

BACKGROUND Anti-melanoma differentiation-associated gene 5 antibody-positive(anti-MDA5 Ab+)dermatomyositis complicated with rapidly progressive interstitial lung disease(anti-MDA5 Ab+DM-RP-ILD)has an unclear underlying mechanism with no recommended unified treatment plan.Herein,one of the cases that we report(Case 2)was successfully treated with tocilizumab despite having lung infection.CASE SUMMARY Case 1 was a 30-year-old woman who was admitted due to recurrent rash for 5 mo,fever and cough for 1 mo,and chest tightness for 3 d.She was diagnosed with non-myopathic dermatomyositis(anti-MDA5 Ab+)and interstitial pneumonia,and was treated with the combination of hormone therapy and cyclophosphamide followed by oral tacrolimus.Case 2 was a 31-year-old man admitted due to systemic rash accompanied by muscle weakness of limbs for more than 1 mo,and chest tightness and dry cough for 4 d.He was diagnosed with dermatomyositis(anti-MDA5 Ab+)and acute interstitial pneumonia with Pneumocystis jirovecii and Aspergillus fumigatus infections and was treated with hormone therapy(without cyclophosphamide)and the combination of tocilizumab and tacrolimus.The condition of both patients eventually improved and they were discharged and showed clinically stable condition at the latest follow-up.CONCLUSION Tocilizumab could be a salvage treatment for patients with anti-MDA5 Ab+DMRP-ILD who are refractory to intensive immunosuppression.

关键词： Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis Progressive interstitial lung disease Interstitial lung disease Tocilizumab Case report

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Successful treatment of rapidly progressive interstitial lung disease complicated by a refractory pneumomediastinum in a patient with anti-MDA5 antibody-positive dermatomyositis

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Rheumatology & Autoimmunity 2023年第4期3卷 240-243页

作者： Lili Jiang Hong Chen Lihua Duan Department of Rheumatology and Clinical Immunology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxiChina

Introduction:Anti-melanoma differentiation-associated gene 5-positive dermatomyositis(anti-MDA5+DM)is a distinct subtype of DM,which is characterized by typical cutaneous features,minimal or no muscle involvement and notable interstitial lung disease,which typically progresses rapidly and has a high mortality.Spontaneous pneumomediastinum(PNM),a relatively unusual but serious complication of anti-MDA5+DM,further increases mortality.Currently,there is no generally accepted treatment regimen for anti-MDA5+DM-associated PNM.Case Description:A 53-year-old man with anti-MDA5+DM presented with rapidly progressive interstitial lung disease that progressed to diffuse subcutaneous emphysema and PNM despite aggressive immunosuppressive therapies.He responded well to combined anti-infection treatments,moderate immunotherapy,and continuous oxygen therapy.Conclusion:Comprehensive screening for potential infections,as well as close monitoring of the patient's immune status is essential for individualizing treatment and maximizing prognosis.

关键词： anti-melanoma differentiation-associated protein 5 antibody dermatomyositis interstitial lung diseases pneumomediastinum

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dermatomyositis and polymyositis in total hip arthroplasty

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World Journal of Orthopedics 2021年第6期12卷 395-402页

作者： Samuel Rosas Michael Schallmo Anirudh Krishna Gowd Matthew Reynolds Akelman T David Luo Cynthia Lynn Emory Johannes Frank Plate Department of Orthopedic Surgery Wake Forest School of MedicineWinston SalemNC 27101United States Department of Orthopedic Surgery Atrium HealthcareCharlotteNC 28203United States

BACKGROUND Idiopathic inflammatory myopathies(IIM)are systemic autoimmune disorders such as dermatomyositis(DM),polymyositis(PM),inclusion body myopathy,and autoimmune necrotizing myopathy that,similar to osteoarthritis,affect quality of life and activities of daily living.Moreover,these patients are often burdened with chronic pain and disability;however,the outcomes and risk of total hip arthroplasty(THA)in this patient population remain unclear.AIM To evaluate 90-d complications and costs in patients with these conditions.METHODS A retrospective case control study was designed by accessing data from the Medicare dataset available on the PearlDiver server.Patients with IIM,here,those with DM and PM were matched based on possible confounding variables to a cohort without these diseases and with the same 10-year risk of mortality as defined by the Charlson Comorbidity Index Score(CCI).Univariate and multivariate analysis were performed to evaluate complications and t-tests to evaluate 90-d Medicare reimbursements as markers of costs after THA.RESULTS The total sample was 1090 patients with each cohort comprised of 545.Females were 74.9%of the population.The mean CCI was 5.89(SD 2.11).Those with IIM had increased rates of pneumonia[odds ratio(OR)1.45,P<0.001]and pulmonary embolism(OR 1.46,P=0.035)and decreased hematoma risks(OR 0.58,P=0.00).90-d costs were on average$1411 greater for those with IIM yet not significantly different(P=0.034).CONCLUSION Patients with IIM have an increased 90-d rate of pneumonia and pulmonary embolism concomitant with a decreased hematoma rate consistent with their procoagulatory state.Further attention to increased resource utilization in these patients is also warranted.

关键词： dermatomyositis Arthroplasty Polymyositis Outcomes Charges Reimbursement

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dermatomyositis Post COVID-19 Vaccine: A Case Report

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Open Journal of Rheumatology and Autoimmune Diseases 2022年第2期12卷 65-70页

作者： Giovana Gabriela Koptian Dalianna Luise Andrade Souto Rodrigues Luiz Felipe Adsuara de Sousa Dawton Yukito Torigoe Division of Rheumatology Faculdade de Medicina da Santa Casa de Sao Paulo Sao Paulo Brazil

dermatomyositis (DM) is a rare systemic autoimmune disease characterized by symmetrical and predominantly proximal muscle weakness in the limbs, associated with typical skin lesions. Autoimmune diseases have already been described as an adverse effect of vaccines. Case-report: A 65-year-old Caucasian female patient evolved, 5 days after the first dose of the AZD1222 vaccine against the COVID-19 virus, with skin lesions suggesting heliotrope and Gottron’s sign, with partial improvement of the condition with use of topical glucocorticoids in the lesions. After two months, the patient received the second dose of AZD1222 vaccine, and evolved with proximal muscle weakness of upper and lower limbs, dysphagia, increase of muscle enzymes, in addition to skin lesions compatible with heliotrope and Gottron’s sign again. After treatment with pulse therapy with methylprednisolone 1000 mg per day for three days and treatment with immunosuppressants, she evolved with significant clinical improvement. Conclusions: This case-report demonstrating an important chronological relationship between dermatomyositis and the vaccine AZD1222 alerts to the possibility of the disease as an important adverse reaction of vaccine against COVID-19 virus, as has been recently described by other authors.

关键词： COVID-19 Vaccine dermatomyositis Systemic Autoimmune Myopathies

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Predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis or dermatomyositis： a retrospective study

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Chinese Medical Journal 2010年第5期123卷 517-522页

作者： JI Su-yun ZENG Fan-qin GUO Qing TAN Guo-zhen TANG Hong-feng LUO Yi-jin TANG Zeng-qi HAN Yan-fang Department of Dermatology Second Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510120 China

Background Interstitial lung disease （ILD） is a serious lung complication in polymyositis （PM） and dermatomyositis （DM） which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM （ADM）. Methods From January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD （69 patients） and a non-lLD group （128 patients）. The clinical features, laboratory findings, and prognosis were compared. Results The multivariate analysis indicated that older age at onset （OR 1.033, 95%C/1.009-1.058, P=0.007）, fever （OR 4.109, 95%CI 1.926-8.767, P 〈0.001） and arthritis/arthralgia （OR 2.274, 95%C/1.101-4.695, P=0.026） were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever （OR 4.912, 95%CI 2.121-11.376, P 〈0.001） was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset （RR 0.122, 95%CI 0.049-0.399, P 〈0.001）, ADM/DM/PM-ILD （RR 0.140, 95%C/0.031-0.476, P=0.002）, cardiac involvement （RR 4.654, 95%CI 1.391-15.577, P=-0.013） and serum albumin level （RR 0.910, 95%CI 0.831-0.997, P=-0.042）. Conclusions Patients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.

关键词： dermatomyositis polymyositis lung diseases, interstitial

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