Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Correlation Analysis Between Changes of D-Dimer Level and Rheumatoid Arthritis Complicated with Interstitial Lung Disease

Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients complicated with interstitial lung disease(interstitial lung disease group),20 rheumatoid arthritis patients without interstitial lung disease(without interstitial lung disease group),and 20 healthy people(control group)in Xijing Hospital were selected for this study.The fasting venous blood of the three groups of subjects was collected and their D-dimer,C-reactive protein(CRP),rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)were detected.Subsequently,the correlation between each index and rheumatoid arthritis complicated with interstitial lung disease was analyzed.Results:The D-dimer level of the interstitial lung disease group was significantly higher than the other two groups(P<0.05).The D-dimer level of the group without interstitial lung disease was significantly higher than the control group(P<0.05).CRP levels in the interstitial lung disease group and the group without interstitial lung disease were significantly higher than those of the control group(P<0.05).The ESR and RF levels of the interstitial lung disease group were significantly higher than the other two groups(P<0.05).The levels of ESR and RF levels of the group without interstitial lung disease were significantly higher than the control group(P<0.05).Conclusion:D-dimer levels of rheumatoid arthritis patients are higher than those of healthy individuals,and those complicated with interstitial lung disease present even higher levels.This finding shows that there is a correlation between D-dimer levels and rheumatoid arthritis with interstitial lung disease,which may facilitate the evaluation and diagnosis of this disease.

Nodular Pulmonary Amyloidosis with Interstitial Lung Disease—Case Report and Literature Review

Amyloidosis is a rare spectrum of disease which involves deposition of misfolded extracellular proteins (amyloids) in various body organs leading to progressive organ dysfunction. Clinical presentation can be variable depending on the organ involved and type of protein. Amyloidosis can be classified based on quantity, type, and location of these proteins. Amyloid light-chain amyloidosis develops in the bone marrow, producing abnormal forms of light-chain proteins, which cannot be broken down. These proteins transform into amyloid fibrils and form amyloid deposits in different organs. Pulmonary amyloidosis is uncommonly diagnosed since it is rarely symptomatic. Diagnosis of pulmonary amyloidosis is usually made in the setting of systemic amyloidosis;however, it may present as localised pulmonary disease. Localized pulmonary Amyloidosis can present as nodular, cystic, or tracheobronchial amyloidosis. Depending on the degree of the interstitial involvement, it may affect alveolar gas exchange and cause respiratory symptoms. This is a case of a 47-year-old female with background history of interstitial lung disease presenting with progressive shortness of breath. Computed tomography scan revealed bilateral pulmonary nodules. The patient was referred to our thoracic surgery team with the suspicion of bronchogenic malignancy with metastasis. Diagnostic video assisted wedge resection was performed for this patient, and histology confirmed pulmonary amyloidosis of nodular type. Amyloid deposition simulates both inflammatory and neoplastic conditions. Definitive diagnosis requires biopsy confirmation therefore early detection and commencing the patient on appropriate treatment pathway may help in symptomatic relief and better outcome.

Acute exacerbation of interstitial lung disease in the intensive care unit:Principles of diagnostic evaluation and management

Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Association between the Lung Immune Prognostic Index and mortality in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Interstitial lung disease and diabetes

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence has beensteadily increasing all over the world. DM and its associated micro andmacrovascular complications result in significant morbidity and mortality. Themicrovascular complications are usually manifested as retinopathy, neuropathy,nephropathy and macrovascular complications generally affect the cardiovascularsystem. In addition to these complications, DM also affects the lungs because of itsrich vascularity and abundance in connective tissue (collagen and elastin). DMhas been found to cause microvascular complications and proliferation ofextracellular connective tissue in the lungs, leading to decline in lung function in arestrictive pattern. Interstitial lung disease (ILD) includes a diverse group ofdisease conditions characterized by different degrees of inflammation and fibrosisin the pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of thecommon type of idiopathic interstitial pneumonia with a high mortality rate. IPFis characterized by chronic progressive fibrosis leading to progressive respiratoryfailure. In this review we focus on lung as the target organ in DM and theassociation of DM and ILD with special emphasis on IPF.

Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease

Objective To evaluate the clinical characteristics and prognostic predictors of patients with diffuse alveolar hemorrhage(DAH)and/or interstitial lung disease(ILD)secondary to microscopic polyangiitis(MPA)in a Chinese general hospital.Methods We retrospectively reviewed the medical records of MPA patients admitted to internal medicine departments between the year 2002 and 2012.The patients were divided into the ILD,DAH,DAH combined with ILD(DAHILD),and no pulmonary involvement(NPI)groups according to pulmonary involvement patterns.The clinical characteristics at diagnosis were analyzed.The risk factors associated with short-term death and long-term death were identified with Logistic regression and Cox analysis.Results Of 193 newly diagnosed MPA patients,181 patients were enrolled in the research,of which 19 had DAH alone,96 had ILD alone,18 had DAH and DAH concurrently,and 48 had NPI.The median of serum creatine level in the DAH group was 449μmol/L,significantly higher than that in the ILD group(123μmol/L,Nemenyi=-35.215,P=0.045)and DAHILD group(359μmol/L,Nemenyi=-43.609,P=0.007).The median follow-up time was 67(range:1-199)months.Patients in the ILD group were older than those in the DAH group(median:69 years vs.57 years,Nemenyi=43.853,P=0.005).The patients with both DAH and ILD had combined features of the two subtypes,and the highest mortality(72.2%at the end of follow-up).The elevated white blood cell count was a risk factor for short-term death(OR=1.103,95%CI:1.008-1.207,P=0.032 for one month;OR=1.103,95%CI:1.026-1.186,P=0.008 for one year).Old age(HR=1.044,95%CI:1.023-1.066,P<0.001),cardiovascular system involvement(HR=2.093,95%CI:1.195-3.665,P=0.010),poor renal function(HR=1.001,95%CI:1.000-1.002,P=0.032)were risk factors for long-term death.Pulmonary infections(38/54)were the leading causes of death,especially for the patients with ILD.Besides,49 patients suffered from pulmonary infections in the first year after diagnosis.Conclusions MPA patients who presented with different pulmonary involvement patterns have completely different clinical features.These subtypes probably have different pathogenesis and should be studied separately.

Vedolizumab-associated diffuse interstitial lung disease in patients with ulcerative colitis:A case report

BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.

Interstitial lung disease induced by the roots of Achyranthes japonica Nakai:Three case reports

BACKGROUND The roots of Achyranthes japonica Nakai(AJN),called“Useul-puli,”has been traditionally used to control pain and improve dysfunction in osteoarthritis patients in South Korea.CASE SUMMARY We described 3 patients diagnosed with herbal medicine induced interstitial lung disease after consuming boiled the roots of AJN.They were referred to our hospital because of the modified Medical Research Council grade 4 dyspnea.Chest computed tomography showed bilateral ground-glass opacities with patchy consolidation.After treatment with systemic glucocorticoid therapy and discontinuation of the roots of AJN,their symptoms improved,and almost all ground-glass opacities and patchy consolidations on chest radiography and chest computed tomography resolved.CONCLUSION We present three cases of interstitial lung disease induced by the roots of AJN.

Meta-analysis of clinical efficacy and safety of kidney Tonifying therapy in the treatment of interstitial lung disease

Objective:To evaluate the efficacy and safety of kidney tonifying therapy in the treatment of Interstitial Lung Disease(ILD).Methods:We searched Wanfang Data,CNKI,CBM,VIP,Pub Med,EMBASE,Web of science and Cochrane Library for Randomized Controlled Trials(RCTs)of kidney tonifying therapy in the treatment of ILD.The retrieval time was from the establishment of the database to December 15,2020.Rev man 5.3 software was used to analyze and summarize the collected literature,and the methodological quality of the included studies was evaluated by the bias risk assessment scale of Cochrane Collaboration Network.Results:A total of 15 articles with 1045 patients were included.The results of meta-analysis showed that compared with the control group treated with conventional western medicine alone,kidney tonifying therapy or combined with conventional western medicine was beneficial to improve the clinical total effective rate[RR=1.33(95%CI 1.24-1.43),P<0.00001].At the same time,compared with the control group treated with routine western medicine,kidney tonifying therapy or combined with routine western medicine can improve cough and wheezing symptoms of patients[MD=-0.62(95%CI-0.78~-0.46),P<0.00001]and MD=-0.79(95%CI-0.18~-0.49),P<0.00001].However,there was no significant improvement in 6-minute walk test and lung function(DLCO%)(P>0.05);only one study reported 7 patients with adverse reactions,but after corresponding treatment,the symptoms were significantly relieved.The analysis of the characteristics of intervention measures in the treatment group showed that there were a total of 80 traditional Chinese medicines involved,of which Shu Dihuang appeared the most frequently,and the tonic drugs were used the most.The two meridians of the lung and kidney appear most frequently.Among the four qi and five flavors,warm and sweet medicines have the highest frequency.Conclusion:Adopting kidney-tonifying method or combined with conventional Western medicine treatment can improve the total clinical effectiveness of patients.Adopting kidney-tonifying method or combined with conventional Western medicine treatment to improve symptoms such as coughing and wheezing.No serious adverse reactions have been reported,and the safety is reliable.Due to the low quality of the included literature,the results of this study need to be verified by high-quality,large sample randomized controlled trials.

Acute exacerbation of interstitial lung disease in the intensive care unit

Acute exacerbations of interstitial lung disease(AE-ILD)represent an acute,frequent and often highly morbid event in the disease course of ILD patients.Admission in the intensive care unit(ICU)is very common and the need for mechanical ventilation arises early.While non-invasive ventilation has shown promise in staving off intubation in selected patients,it is unclear whether mechanical ventilation can alter the exacerbation course unless it is a bridge to lung transplantation.Risk stratification using clinical and radiographic findings,and early palliative care involvement,are important in ICU care.In this review,we discuss many of the pathophysiological aspects of AE-ILD and raise the hypothesis that ventilation strategies used in acute respiratory distress syndrome might be implemented in AE-ILD.We present possible decision-making and management algorithms that can be used by the intensivist when caring for these patients.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis

Background:Programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)inhibitors have become integral elements within the current landscape of breast cancer treatment modalities;however,they are associ-ated with interstitial lung disease(ILD),which is rare but potentially fatal.Notably,only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors.Therefore,this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors.We also reported three cases of ILD after PD-1 inhibitor treatment.Methods:We comprehensively searched PubMed,EMBASE,and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer.Pooled overall estimates of incidence and risk ratio(RR)were calculated with a 95%confidence interval(CI),and a mirror group analysis was per-formed using eligible studies.Results:This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment.A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors(0.05 vs.0.02).The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors(RR=2.34,95%CI,1.13-4.82,P=0.02).Conclusion:Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors.These findings are instrumental for clinicians in treatment deliberations,and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

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

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.

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

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.

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

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.

Anti-melanoma differentiation-associated gene 5 and anti-Ro52 antibody-dual positive dermatomyositis accompanied by rapidly lung disease:Three case reports

BACKGROUND Clinically amyopathic deramatomyositis was manifested as the various cutaneous dermatomyositis(DM)manifestations without muscle weakness.Anti-melanoma differentiation-associated gene 5(anti-MDA5)and anti-Ro52 antibody-dual positive clinically amyopathic DM patients are at a high risk of developing rapidly progressive interstitial lung disease,and they exhibit an immensely high half-year mortality.CASE SUMMARY We presented three patients with anti-MDA5 and anti-Ro52 antibody-dual positive DM patients and we reviewed the previous studies on the link between anti-MDA5 and anti-Ro52 antibody-dual positive DM.Although we aggressively treated these patients similarly,but they all exhibited different prognoses.We reviewed the importance of clinical cutaneous rashes as well as the pathogenesis and treatment in the dual positive anti-MDA5 and anti-Ro52 associated DM.CONCLUSION Patients with anti-MDA5 anti-Ro52 antibody-dual positive DM should be accurately diagnosed at an early stage and should be treated aggressively,thus,the patient’s prognosis can be significantly modified.