Clinical,Radiological And Pathological Features And Prognosis Of 41 Patients With Anti-NXP2 IgG Positive Dermatomyositis

Background and objectiveDermatomyositis(DM)is an acquired,heterogeneous autoimmune disease characterized by muscle weakness and skin lesions,as well as multiple systemic involvement.Anti-nuclear matrix protein 2(NXP2)antibody is one of the dermatomyositis-specific antibodies(DMSA).Given that there are differences such as subcutaneous edema,skin rash,subcutaneous calcification and malignancy in many studies on anti-NXP2 antibody-positive DM worldwide.This study was aimed to analyze the clinical features,muscle imaging findings,pathology characteristics,treatment and prognosis of DM with anti-NXP2 antibody in our neuromuscular center.MethodsThis was a single-center retrospective observational study on DM patients admitted to Qilu hospital of Shandong University from January 2010 to June 2022.All patients were performed muscle biopsy and were confirmed by myositis antibody detections(Immunoblotting or western blotting)with positive anti-NXP2 antibody.All enrolled patients were met the diagnostic criteria of the 119th European Neuromuscular Center(ENMC).Clinical features,muscle imaging changes,muscle pathological features,treatment and prognosis were comprehensively summarized and compared with cohorts reported by other centers at home and abroad.Results1.Clinical features:41 anti-NXP2 antibody-positive DM patients were enrolled.There were 22 females(53.7%)and 19 males(46.3%).The patients’ median age of onset was 28 years old,ranging from 3 to 72 years old.16 patients(39.0%)were juvenile dermatomyositis(JDM).All patients showed proximal muscle weakness,22 patients’(53.7%)proximal muscle strength assessed by manual muscle strength test(MMT)turned out to be grade 3 or lower.23 patients(56.1%)had dysphagia,and 3 patients(7.3%)had malignancy.There were 12 patients(29.3%)and 28 patients(68.3%)complicated with limb edema and rash,respectively.No Subcutaneous calcification was found.The maximum value of CK was 31115.0 U/L,the minimum value of CK was 64.0 U/L,the median value of CK was 1700.5U/L.2.Imaging features:Magnetic resonance imaging(MRI)of thigh muscles was performed in 13 patients.The thigh muscles showed extensive edema changes,among which the average edema score of anterolateral thigh was the highest,and the proportion of edema of the biceps femoris long head was the lowest,which was 62.54%.7 cases(53.85%)had myofascial edema and 4 cases(30.77%)had subcutaneous edema.The overall fatty infiltration was lighter than edema,and the mean fatty infiltration score in the posterior thigh was the highest.3.Pathological features:Perifascicular atrophy(PFA)were found in 18/41 patients(43.90%);17/41 patients(41.46%)showed cytochrome c oxidase(COX)activity deficiency of perifascicular area.51.22%showed focal inflammatory cell infiltration in perivascular or perifascicular area.Muscle fiber cytoplasm expression of myxovirus resistance protein A(MxA)were found in 29/37 cases(78.38%),with 23/37 cases(62.16%)expressed in perifascicular area.28/40 cases(70%)showed membrane attack complex(MAC)deposited on the capillaries.Positive expression on sarcolemma of non-necrotic fibers of major histocompatibility complex class I(MHC-1)antibody was observed in 38/41 cases(92.68%),with diffuse expression in 32/41 cases(78.05%).No CD8 positive T-lymphocytes were found to surround or invade non-necrotic muscle fibers.4.Treatment and prognosis:41 patients were systematically followed up.The longest follow-up time was 146 months,the shortest was 11 months,and the median follow-up time was 57 months.1 patient was diagnosed with DM as well as extensive malignant metastases and didn’t receive treatment.24/40 patients(60%)received glucocorticoids combined with immunosuppressant and/or immunoglobulin,and 16/40 patients(40%)received glucocorticoids alone.8 patients(26.67%)relapsed.11/41 patients(26.83%)died,including 4 cases due to severe pulmonary infection,3 cases for malignancy,2 cases for pulmonary infection with acute gastrointestinal bleeding,1 for heart failure,and 1 was not clear.The proportion of myalgia and dysphagia in patients who died was significantly higher than that in surviving patients.All of the 30 surviving patients had a favorable outcome up to the last follow-up.Conclusion1.Anti-NXP2 antibody-positive DM can occur in both adult and child.The main manifestation is severe proximal muscle weakness,dysphagia and myalgia.The proportion of patients with subcutaneous edema and skin rash in our cohort is low,and no subcutaneous calcification was observed in our cohort.2.MRI reveals that muscle oedema is more pronounced than fatty infiltration,and with no obvious selectivity.The proportion of subcutaneous edema is relatively low,but myofascial edema is more pronounced.3.The main pathological findings of muscle biopsies are positive expression of MxA in the cytoplasm of muscle fibers and diffused expression of MHC-1 in non-necrotic muscle fiber membrane.The proportion of PFA is relatively low.4.Anti-NXP2 antibody-positive DM has a high mortality rate,of which severe pulmonary infection,active gastrointestinal bleeding and malignancy are the main causes of death.Dead patients are more likely to have myalgia and dysphagia during disease onset.