Clinical And Pathological Research Of Immune-mediated Necrotizing Myopathy

PART?Clinical and pathological features of immune-mediated necrotizing myopathy with positive anti-SRP antibody Objective: To investigate the clinical and pathological features of immune-mediated necrotizing myopathy with positive anti-signal recognition particle(SRP)antibody.Methods: Fourty patients with anti-SRP myopathy were admitted to our department from January 2014 to January 2018,and all patients underwent muscle biopsy after admission and recieved immunosuppressive treatment.Clinical data of 40 patients were collected in detail,including demographic information,clinical characteristics and auxiliary examination results.The patients were divided into acute group,subacute group and chronic group according to the onset of the disease and their clinical and pathological characteristics were compared.Muscle biopsy tissues of all patients were stained with hematoxylin-eosin,and immunohistochemical staining was performed for the expression of surface markers of lymphocytes and macrophages,major histocompatibility complex class I molecules(MHC-I)and membrane attack complex(MAC).Results: The ratio of male to female patients with anti-SRP myopathy was 1:3,the peak age of onset was 40-50 years old,and summer was the season of high incidence(50%).All patients had limb weakness and increased serum creatine kinase levels(649-16013IU/L)in varying degrees,and proximal limb weakness was predominant.47.5% of patients suffered from severe muscle weakness;42.5% and 30% of patients had myalgia and muscle atrophy,respectively;35% and 12.5% of patients suffered from dysphagia and dyspnea,respectively.Twenty percent of the patients had interstitial lung changes,while other extramuscular involvement such as rash,fever and Raynaud's phenomenon were uncommon.The proportion of patients with severe muscle weakness in acute group was significantly higher than that in subacute group(P=0.026);muscle atrophy in chronic group was significantly more common than that in acute group(P=0.032),and myalgia less common than that in acute group(P=0.036);the therapeutic effect in chronic group was significantly worse than that in subacute group(P=0.026).Patients may have different degrees of muscle fiber necrosis,regeneration and inflammatory cells infiltration.Macrophages were the most important inflammatory cells,in which CD163+M2 type macrophages dominated,followed by scattered CD4+T cells,while CD8+T cells and CD20+B cells are rare.The positive expression of MHC-I molecule and the deposition of C5b-9 on non-necrotizing muscle fibers can be seen in most patients.Conclusion: Anti-SRP myopathy patients were more common in 40-50 year-olds and in women,with a high incidence in summer.Severe muscle involvement and elevated creatine kinase levels were prominent clinical manifestations.The treatment effect in the chronic group was relatively poor.All patients showed varying degrees of muscle fiber necrosis and regeneration,and M2 type macrophages were the main inflammatory cells.Positive expression of MHC-I and C5b-9 deposition were observed on the muscle fiber of most patients.PART? The efficacy and safety of coadministration of tacrolimus with corticosteroids in patients with immune-mediated necrotizing myopathyObjective: To assess the efficacy and safety of tacrolimus in combination with corticosteroids in patients with immune-mediated necrotizing myopathy.Methods: The medical records of 20 hospitalized patients with immune-mediated necrotizing myopathy(IMNM)who had received tacrolimus combined with oral prednisone from January 2014 to August 2017 were retrospectively reviewed.The recruited patients were shifted to the combined therapy because they failed to respond well to monotherapy with oral prednisone.The clinical efficacy during a mean duration of follow-up of 21 months(range,14-24 months)was assessed by evaluating the changes of serum creatine kinase(CK)levels,the Medical Research Council(MRC)grading of the weakest muscle groups and dosage of oral prednisone.Adverse effects were monitored to assess the safety of tacrolimus.Results: After starting tacrolimus,most of the 20 patients showed significant improvement in muscle strength and remarkable decline in serum CK levels at the follow-up points(p<0.0001).In addition,the daily dosage of prednisone was statistically significantly reduced(p<0.0001)after the combination therapy.No serious adverse events attributable to tacrolimus occurred in the patients.Conclusion: Early coadministration of tacrolimus with corticosteroids promoted the remission and recovery of patients with IMNM and seemed to be a relatively safe treatment program for physicians managing immune-mediated necrotizing myopathy.