Clinical Characteristics in Pediatric Patients with Immune-Mediated Necrotizing Myopathy

Clinical Characteristics in Pediatric Patients with Immune-Mediated Necrotizing Myopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Characteristics in Pediatric Patients with Immune-Mediated Necrotizing Myopathy Yiwen Xu, Zhanwei Zhang, Yixuan Chu, Fang He, Leilei Mao, Li Yang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7777355/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Objective To investigate the clinical characteristics and therapeutic strategies of childhood immune-mediated necrotizing myopathy (IMNM) and to provide evidence for clinical diagnosis and management. Methods We retrospectively analyzedthe clinical data of 10 children diagnosed with IMNM at the Children's Medical Center, Xiangya Hospital, Central South University, from January 2016 to May 2025. The onset features, clinical manifestations, laboratory findings, muscle magnetic resonance imaging (MRI) characteristics, treatment modalities, and prognosis were summarized. Results Among the 10 patients, 4 were male and 6 were female, with a median age at onset of 5.5 years (range: 3–16 years). The mainclinical manifestations included symmetric proximal muscle weakness (100%) and cutaneous manifestations(50%, including Gottron's sign and periorbital rash). Creatine kinase(CK) levels were markedly elevated, with a median of 3988.5 U/L (range: 2080–13524 U/L). Muscle MRI revealed edema or fatty infiltration in the thigh muscles. Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies were detected in 4 patients (40%), and anti-signal recognition particle(SRP) antibodies in 6 patients (60%). Electromyography (EMG) showed myopathic changes in all cases. Muscle histopathology demonstrated myofiber necrosis, regeneration, and inflammatory cell infiltration. All patients received glucocorticoid therapy, combined with oral methotrexate. Additionally, 5 patients were treated with rituximab, and 8 received intravenous immunoglobulin (IVIG). During follow-up, 4 patients achieved complete remission, 5 achieved partial remission, and 1 showed noclinical remission. Conclusion Childhood IMNM is characterized by proximal muscle weakness, typical rash, and significantly elevated CK levels, frequently associated with anti-SRP or anti-HMGCR antibodies. Early immunosuppressive therapy, including glucocorticoids combined with immunosuppressants or IVIG, can significantly improve prognosis, emphasizingthe importance of early diagnosis and active intervention. Immune-mediated necrotizing myopathy Children Anti-SRP antibody Anti-HMGCR antibody Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune disorders characterized by chronic muscle inflammation and weakness. These conditions include dermatomyositis (DM), polymyositis (PM), antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). The principal clinical manifestations of IIMs encompass symmetric proximal muscle weakness, elevated serum muscle enzyme levels, presence of autoantibodies, and inflammatory cell infiltration in muscle histopathology. The disease exhibits two peak incidence periods: 45–60 years and 5–15 years, with a higher prevalence in adult [ 1 ]. At the 119th international workshop of the European Neuromuscular Centre (ENMC), the sub-group of ‘IMNM’ emerged as a separate entity among IIMs for the first time based on pathological criteria [ 2 ]. The characteristics of IMNM has some similarity with IIMs, but it progresses more rapidly. Among pediatric patients, the morbidity of IMNM is less than juvenile dermatomyositis (JDM) in juvenile IIMs. One previous research stated that pediatric IMNM accounts for just 2.9% in 440 juvenile IIMs, which is significantly lower than that in adults IMNM [ 3 ]. With more and more acknowledge of IMNM, it is further subdivided into three subtypes based on the presence of myositis-specific autoantibodies (MSAs) according to the 2016 ENMC classification criteria: anti-signal recognition particle (SRP) antibody-positive, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive, and seronegative cases[ 4 ]. However, comprehensive data on the clinical spectrum and outcomes of pediatric IMNM remain limited. While substantial clinical data exist regarding adult IMNM, including its clinical features, treatment modalities, and prognostic factors, evidence on pediatric IMNM remains limited. This study presents a retrospective analysis of clinical data from 10 pediatric patients diagnosed with IMNM, aiming to describe the clinical manifestations, serological profiles, therapeutic strategies, and outcomes. The findings are intended to enhance clinical awareness of pediatric IMNM, facilitate early diagnosis, guide individualized treatment, and provide a foundation for future prospective research on this rare condition. Methods Diagnostic criteria and patient enrollment Clinical data were retrospectively collected and analyzed from pediatric patients diagnosed with IMNM at Xiangya Hospital between January 2016 and May 2025. The data encompassed clinical presentations, laboratory findings, treatment regimens, and outcomes. Cases meeting the established diagnostic criteria for IMNM were included, which consist of clinical features of myopathy, elevated creatine kinase levels, and seropositivity for specific autoantibodies [4]. In addition, targeted genetic sequencing for common childhood-onset muscular dystrophies, including mutations in the DMD gene, was conducted to exclude inherited myopathies. Informed consent was obtained from all patients' legal guardians, and the study was approved by the Ethics Committee of Xiangya Hospital, conducted in accordance with the principles of the Declaration of Helsinki. Antibodies detection Serum myositis autoantibodies were detected using Euroimmun immunoblot assays, following the manufacturer’s instructions as previously described [5]. The panel included anti-Mi-2, anti-TIF1γ, anti-NXP2, anti-Ku, anti-PM-Scl75, anti-PM-Scl100, anti-SRP, anti-PL-7, anti-PL-12, anti-OJ, anti-cN-1A, anti-MDA5, anti-SAE1, anti-Jo-1, anti-EJ, anti-Ro-52, and anti-HMGCR antibodies. Immunoblot results were interpreted as weakly positive (+), positive (++), or strongly positive (+++) based on the intensity of the reaction bands. Muscle magnetic resonance imaging parameters Muscle magnetic resonance imaging (MRI) was performed using either a 1.5 Tesla or 3.0 Tesla scanner (Siemens, Erlangen, Germany) at Xiangya Hospital. The MRI protocol included coronal and axial T1-weighted, T2-weighted, and short-tau inversion recovery (STIR) sequences. Imaging parameters were as follows: T1-weighted—repetition time (TR) 480 ms, echo time (TE) 13 ms, slice thickness 4 mm; T2-weighted—TR 3280 ms, TE 65 ms, slice thickness 4 mm. Assessment of muscular fatty infiltration and edema The degree of fatty infiltration was assessed on T1-weighted images based on a previously established classification system [6], modified and categorized into six grades: 0, normal; 1, scattered signals; 2, mild abnormalities (60% fatty infiltration); 5, complete replacement of muscle tissue by fatty infiltration. Muscle edema was graded based on STIR sequences using a six-point scale as follows [7]: 0, normal; 1, scattered high signals without fusion; 2, slightly high scattered or small sheet-like signals involving less than 50% of the muscle; 3, higher scattered or small sheet-like signals involving less than 50%; 4, slightly high scattered or small sheet-like signals involving more than 50%; 5, higher scattered or small sheet-like signals involving more than 50%. Muscle biopsy Muscle biopsy specimens were obtained, frozen, sectioned, and fixed. Subsequently, they were stained with hematoxylin and eosin (HE) and immunostained with antibodies against C5b-9, CD4, CD8, CD20, CD68, major histocompatibility complex class I (MHC-I), and dystrophin (rod domain). Acid-fast staining techniques were employed to detect structural abnormalities in muscle biopsies. Nicotinamide adenine dinucleotide hydrogenase (NADH) staining was performed to evaluate mitochondrial enzyme activity and the internal architecture of muscle fibers [8]. Follow up and outcome From January 2016 to May 2025, a total of 10 patients were followed up. During the follow-up period, manual muscle testing (MMT) (Table 1) [9] and quality of life assessment using the modified Rankin Scale (mRS) (Table 2) [10, 11]were performed, with initial, best, and final mRS scores documented. Patients with cervical muscle involvement were classified as having axial muscle weakness, while the remaining patients were categorized as having limb muscle involvements. Treatment outcomes were classified as complete remission, partial remission, or no significant improvement. Complete remission was defined as an mRS score of 0, partial remission as an mRS score of 1, and no significant improvement as an mRS score of 3 . Table 1 The Manual Muscle Testing (MMT) Grade Description 0 No contraction 1 Flicker or trace of contraction 2 Active movement with gravity eliminated 3 Active movement against gravity 4 Active movement against gravity and resistance 5 Normal power Table 2 The modified Rankin Scale (mRS) Rankin Grade Description 0 No symptoms 1 No significant disability: despite symptoms able to carry out all usual duties and activities 2 Slight disability: unable to perform all previous activities but able to look after own affairs without assistance 3 Moderate disability: requiring some help, but able to walk without assistance 4 Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance 5 Severe disability: bedridden, incontinent, and requiring constant nursing care and attention 6 Death Statistical analysis Statistical analysis was conducted using SPSS version 27.0 software. Normally distributed continuous variables were expressed as mean ± standard deviation, whereas non-normally distributed data were presented as median (interquartile range). Results Clinical features Table 3 presents the clinical features of patients diagnosed with immune-mediated necrotizing myopathy (IMNM). A total of 10 patients were included, consisting of 6 females and 4 males. The median age at disease onset was 5.5 years (range: 3–16). Myositis antibody testing revealed that 4 patients were positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody, while the remaining 6 were positive for anti-signal recognition particle (SRP) antibody. Overlapping myositis antibodies were detected in 2 patients with anti-HMGCR and 2 with anti-SRP antibodies. None of the IMNM patients with anti-HMGCR antibodies had prior statin exposure. All 10 patients presented with both upper and lower limb muscle weakness, while isolated lower limb involvement was observed in 1 patient. Axial muscle weakness was documented in 3 patients, manifesting as impaired neck flexion or rotation, weak shoulder shrugging, or abduction. Lower limb myalgia was reported in case 2 and case 6. No patient exhibited respiratory or cardiac symptoms. Gottron’s sign and periorbital rash were observed in 1 patient with anti-HMGCR and 4 patients with anti-SRP antibodies, respectively. Cutaneous manifestations in case 1 and case 5 occurred 10 and 18 months, respectively, prior to the onset of muscle weakness, suggesting that these signs could serve as early indicators of IMNM. Case 1 was also diagnosed with subclinical hypothyroidism. No patient had coexisting rheumatic disease. Laboratory data The median initial creatine kinase (CK) level was 3988.5 U/L (range: 2080–13524 U/L; normal reference range: 50–310 U/L). Elevated CK levels were detected in case 2 and case 4, 9 and 12 months before the onset of muscle weakness, respectively. The median peak and final CK levels were 10228 (range: 2080–16674) U/L and 377.5 (range: 58–2514) U/L, respectively. At the last follow-up, 5 patients had elevated CK levels, and among them, 4 remained asymptomatic or experienced only mild symptoms. In four HMGCR antibody-positive patients, the median initial, highest, and final CK levels were 6280.5 (range: 3270–13524) U/L, 14324.5 (range: 10482–16674) U/L, and 1537.5 (range: 589–1778) U/L, respectively. In contrast, among five SRP antibody-positive patients, the corresponding values were 3171.5 (range: 2080–11836) U/L, 7205.5 (range: 2080–11836) U/L, and 102.5 (range: 58–668) U/L, with two patients exhibiting peak CK levels at disease onset. These data indicate that CK levels in HMGCR antibody-positive patients were higher compared to those in SRP antibody-positive patients during disease progression, and that CK levels in SRP antibody-positive patients largely returned to normal by the end of the disease course (Table 3). Table 3 Clinical features of patients with IMNM Gender Onset of age, year Antibody Muscle weakness Lung disease Cardiac involvement Skin rash Initial CK U/L Highest CK U/L Last CK U/L Case 1 Female 3 HMGCR upper and lower limbs, especially proximal No No Gottron sign in hands 13524 16485 1297 Case 2 Female 6 HMGCR upper and lower limbs, especially proximal cervical muscle No No No 3270 16674 2514 Case 3 Male 3 HMGCR, Mi-2 lower limbs, especially proximal cervical muscle No No No 5804 12164 589 Case 4 Female 12 HMGCR, NXP2, PL-7 upper and lower limbs, especially proximal No No No 6757 10482 1778 Case 5 Male 11 SRP upper and lower limbs, especially proximal No No Periorbital rash, Gottron sign in hands 2080 2080 94 Case 6 Female 5 SRP, PM-Scl 75 upper and lower limbs, especially proximal No No No 2870 9495 111 Case 7 Female 16 SRP upper and lower limbs, especially proximal cervical muscle No No Periorbital purple rash, Gottron sign in hands 11836 11836 668 Case 8 Female 4 SRP, Ro-52, PM-Scl 75 upper and lower limbs, especially proximal No No No 3136 9974 58 Case 9 Male 5 SRP upper and lower limbs, especially proximal No No Periorbital rash, Gottron sign in hands and knees 3207 4201 74 Case 10 Male 11 SRP upper and lower limbs, especially proximal No No Periorbital rash 4707 4916 166 Thigh MRI All patients underwent muscle magnetic resonance imaging (MRI). As shown in Figure 1, thigh MRI revealed muscle edema in 8 of 10 patients, while fatty infiltration was observed in 5 patients (Figure 1, Figure 3). The frequency and mean scores of muscle edema were highest in the adductor magnus, whereas the gluteus maximus showed the highest mean scores and frequency for fatty infiltration (Figure 2, Figure 3). Electromyogram and myopathology Among the ten patients, eight underwent needle electromyography, which all demonstrated myogenic changes. Muscle biopsy results were available for only one HMGCR antibody-positive patient. The biopsy was taken from the left biceps brachii muscle. Hematoxylin and eosin staining revealed marked variation in myofiber size, scattered necrotic and regenerating myofibers, and moderate connective tissue proliferation. NADH dehydrogenase staining showed disruption of the intermyofibrillar network in most myofibers. Acid phosphatase staining demonstrated scattered focal increases in endomysial enzyme activity. No abnormalities were detected on Gomori staining, adenosine monophosphate (AMP) activity, succinate dehydrogenase staining, cytochrome C oxidase and succinate double staining, adenosine triphosphate (ATP) cyclase staining, or PAS and ORO staining. Immunohistochemical analysis for muscular dystrophy and inflammatory myopathy was also performed. In the muscular dystrophy panel, anti-dystrophin-R, -C, -N staining of dystrophin protein in muscle fiber membranes, anti-myosin-α, -β, -γ, -δ staining of myosin protein in the endomysium, and anti-dysferlin staining all showed normal expression. However, the inflammatory myopathy panel revealed characteristic findings: MHC-Ⅰ expression was positive in necrotic myofibers, with numerous CD4-positive lymphocytes, a few CD8-positive lymphocytes, and a few CD68-positive macrophages present in the endomysium, along with partial expression of the C5b-9 membrane attack complex (MAC) in the myofiber cytoplasm. No CD20-positive lymphocytes were observed. (Figure 4) Treatment and outcome All pediatric patients received initial steroid therapy during follow-up until May 2025, including six patients treated with intravenous methylprednisolone pulse therapy and four patients receiving oral prednisone. The median duration of steroid maintenance therapy was 36.5 months (range: 9–74 months). Additionally, these 10 patients received various forms of immunotherapy, including intravenous immunoglobulin (n=9), methotrexate (n=10), rituximab (n=7), mycophenolate mofetil (n=2), tacrolimus (n=2), azathioprine (n=1), telitacicept (n=1), and ofatumumab (n=1). Based on the final modified Rankin Scale (mRS) score, five patients achieved complete remission (mRS=0), four patients showed partial remission (mRS=1), and one patient exhibited no significant remission (mRS=3). Among the five patients with complete remission, two achieved normalization of muscle strength and serum creatine kinase (CK) levels, along with antibody negativity, and were successfully weaned off medication. However, one patient experienced a relapse during the gradual tapering of therapy after achieving normal muscle strength, normal serum CK levels, and antibody negativity, as the signal recognition particle (SRP) antibody reappeared strongly positive (+++). (Table 4, Table 5) Table 4 Treatment and outcome of Patients with IMNM Initial steroid Time of steroid maintenance, months Intravenous immunoglobin Rituximab Other immunotherapies Initial mRS Best mRS Final mRS Case 1 Methylprednisolone pulse therapy 74 a 2g/kg, monthly, 17 times. 1g/kg, once 750mg/m2, twice Hydroxychloroquine, azathioprine, methotrexate a 5 1 1 Case 2 Oral prednisolone 22 2g/kg, monthly, 26 times. 1g/kg, once 750mg/m2, once. 375mg/m2, twice Methotrexate, Mycophenolate mofetil a , tacrolimus, telitacicept, ofatumumab 4 1 1 Case 3 Methylprednisolone pulse therapy 26 a 2g/kg, monthly, 20 times. 1g/kg, monthly, twice 750mg/m2, twice Methotrexate a 2 0 0 Case 4 Methylprednisolone pulse therapy 34 a 2g/kg, monthly, 15 times 750mg/m2, three times Methotrexate a , tacrolimus a 4 1 1 Case 5 Methylprednisolone pulse therapy 36 a 2g/kg, once No Methotrexate a 4 1 1 Case 6 Methylprednisolone pulse therapy 37 2g/kg, monthly, twice 750mg/m2, four times. 375mg/m2, six times Methotrexate, mycophenolate mofetil a 4 1 1 Case 7 Oral prednisolone 9 a 2g/kg, monthly, 6 times No Methotrexate a 4 3 3 Case 8 Oral prednisolone 44 2g/kg, monthly, 6 times No Methotrexate 4 0 0 Case 9 Methylprednisolone pulse therapy 60 2g/kg, monthly, 8 times No Methotrexate 5 0 0 Case 10 Oral prednisolone 71 a No No Methotrexate 3 0 0 a: Maintaining till last visit. Table 5 Treatment of IMNM Patients Treatment methods Total, n(%) Methylprednisolone pulse therapy 6 (60%) Oral prednisolone 4 (40%) Intravenous immunoglobin 9 (90%) Methotrexate 10 (100%) Rituximab 7 (70%) Mycophenolate mofetil 2 (20%) Tacrolimus 2 (20%) Azathioprine 1 (10%) Telitacicept 1 (10%) Ofatumumab 1 (10%) Hydroxychloroquine 1 (10%) Discussion Apart from typical manifestation of IMNM, there are many atypical clinical features in disease progression, such as asymptomatic hyper CK level, limb-girdle muscular dystrophy-like phenotype, facioscapulohumeral muscular dystrophy-like phenotype and distal myopathy phenotype [12]. In this study, we observed all pediatric patients were hospitalized due to limb weakness, primarily presenting with proximal limb involvement, and three patients exhibited axial muscle weakness. Five patients had previously experienced other symptoms for at least one year before the onset of weakness, including elevated serum CK levels or rash like DM’s, which were not recognized or appropriately addressed by their families. Therefore, rash and elevated serum CK levels may manifest early in pediatric IMNM patients; however, there is currently no statistical evidence supporting this observation, which warrants further confirmation through large cohort studies. Based on this finding, in children presenting with unexplained rash and elevated CK levels, even in the absence of weakness, testing for myositis-specific antibodies should be considered to facilitate early diagnosis. Extra muscular manifestations of IMNM in pediatric patients may include rash, heart failure, Raynaud’s phenomenon, interstitial lung disease, and malignancy. In our study, four patients exhibited periorbital rash, but none developed heart failure, Raynaud’s phenomenon, interstitial lung disease, or malignancy. Similarly, a previous retrospective cohort study from a single center in China involving 55 pediatric IMNM patients found no cases with Raynaud’s phenomenon, interstitial lung disease, or malignancy [13]. Therefore, conducting a larger cohort study is necessary to determine the prevalence of extra muscular manifestations among Chinese pediatric patients with IMNM. Many studies demonstrated that statin medicine exposure associates with adult IMNM patients with anti-HMGCR antibodies positive [14, 15, 16]. Statins are widely used to treat dyslipidemia and reduce the risk of cardiovascular diseases, but there is no research reporting the pediatric IMNM exposing to statins. In the study, none of these patients have been exposed to statins, of which the reason may be dyslipidemia and cardiovascular diseases often occur in middle-people and elderly people. The degree of muscle fat infiltration and edema in IMNM is not synchronized. As the disease progresses, the degree of muscle edema gradually decreases, whereas fat infiltration remains stable or worsens. Previous literature lacks descriptions of MRI characteristics in the thigh muscles of pediatric IMNM. In patients with shorter disease duration, thigh muscle edema is the predominant lesion, while those with longer disease duration exhibit higher fat infiltration scores. However, fat infiltration can occur during the early stages of the disease. In this study, fat infiltration primarily affected the gluteus maximus, followed by the adductor magnus, with the most severe fat infiltration observed in the gluteus maximus. The most frequently involved muscle for edema in the thigh was the adductor magnus, followed by the gluteus maximus. This distribution corresponds with the clinical presentation of IMNM, which typically manifests as proximal limb weakness. Although MRI is only one component of the diagnostic criteria for IMNM in antibody-negative patients, clinicians routinely perform muscle MRI during the diagnostic process. This is because the extent of muscle fat infiltration or edema identified by MRI may serve as a marker reflecting disease severity [17]. The diagnostic criteria for IMNM proposed at the 224th International Symposium are categorized into antibody-positive and antibody-negative criteria [4]. In the absence of specific autoantibodies, diagnosis requires integration of muscle pathology, electromyography, and muscle MRI findings. Due to the unique characteristics of pediatric patients, few underwent muscle biopsy, in contrast to adults. This study collected pathological results from only one pediatric case. Case 2 was initially suspected to have muscular dystrophy based on elevated creatine kinase (CK) levels and histopathological findings. However, the diagnosis of IMNM was confirmed after the development of muscle weakness and subsequent detection of muscle inflammation antibodies. This diagnostic challenge arises from overlapping histopathological features between IMNM and muscular dystrophy, leading to frequent misdiagnosis in the early stages. Previous cohort studies have also reported that pediatric IMNM can present with two types of muscle pathology: necrotizing myopathy and features mimicking muscular dystrophy, with the latter being more common[13]. Therefore, in patients presenting with elevated CK levels, testing for myositis-specific antibodies is essential for accurate diagnosis. The typical myopathological features of immune-mediated necrotizing myopathy (IMNM) include myofiber necrosis and regeneration, with or without inflammatory cell infiltration, which constitutes one of the pathological diagnostic criteria [4]. However, these features are not specific to IMNM and can also be observed in other myopathies that involve myofiber necrosis. In addition to the evaluation of routine histological stains under light microscopy, immunohistochemical analysis is required for the diagnosis of antibody-negative IMNM. Currently, there is no consensus regarding the immunohistochemical characteristics of IMNM. A previous study evaluated the sensitivity and specificity of major histocompatibility complex (MHC) class Ⅰ and Ⅱ immunostaining in the diagnosis of idiopathic inflammatory myopathies (IIMs). The findings indicated that upregulation of MHC-Ⅰ expression may represent a nonspecific and common secondary response to muscle injury, whereas MHC-Ⅱ expression in IIM demonstrates high specificity with moderate sensitivity [18]. Increased MHC-Ⅰ expression in muscle fibers is frequently observed in patients positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, supporting the immune-mediated pathogenesis of the disease, although it lacks specificity [19]. In contrast, MHC-Ⅱ expression is rarely detected in IMNM and may serve as one of the exclusion criteria. Complement membrane attack complex (C5b-9) deposition is also commonly observed in patients with anti-HMGCR antibodies, but it may also be present in those with dermatomyositis (DM) and antisynthetase syndrome (ASS) [20]. Although muscle biopsy remains the gold standard for diagnosing IMNM, its pathological features lack specificity. Therefore, a comprehensive diagnostic approach is necessary, incorporating clinical history, physical manifestations, serum creatine kinase (CK) levels, specific antibody testing, and muscle imaging findings. Treatment of IMNM typically involves the administration of glucocorticoids, immunosuppressive agents, immunoglobulins, and biologic targeted therapies. According to the 2022 British Society for Rheumatology Guidelines for Juvenile IIM, high-dose glucocorticoids combined with methotrexate are recommended as first-line therapy for the majority of pediatric patients. Mycophenolate mofetil has demonstrated efficacy in improving both cutaneous and muscular manifestations, whereas intravenous immunoglobulin (IVIG), rituximab, and cyclophosphamide are primarily reserved for cases of severe or refractory IIM [21]. In this study, all pediatric patients received either intravenous or oral glucocorticoids as initial treatment. Oral glucocorticoid therapy plays a significant role in maintenance treatment. Despite the use of minimal glucocorticoid doses during following therapy, it’s side effects cannot been ignored. For the children during the growth and development period the adverse reactions are more significant, with growth and development delay being the most serious [22]. Many parents expressed concern regarding the potential adverse effects of long-term glucocorticoid use on this. Future prospective studies are urgently needed to establish the minimal effective duration of glucocorticoid therapy in pediatric IMNM, aiming to balance efficacy with the minimization of long-term adverse effects on growth and development. In this study, two children got complete remission and drug discontinuance eventually. During the disease progression of patient 8, her CK level decreased to normal, and then started to reduce the dosage of prednisolone three months later, with addition to methotrexate gradually at the same time. Eight months later, she stopped use prednisolone because of the medicine deficiency by herself and her limbs power became worse latterly, relapse happening. However, after reusing the therapy of prednisolone and methotrexate, combining with IVIG for seven months, she started to decrease prednisolone when CK level was normal and antibodies were negative. Whereas, another patient started to reduce prednisolone gradually a month later after the CK level became normal and he did not experience a relapse. Comparing with these two patients’ therapy tragedy, the latter received methylprednisolone pulse and IVIG therapy at the early stage of the onset. A review favors early and aggressive immunotherapy therapy to minimize irreversible damage and fatty replacement of muscles, but these treatments are often not completely effective [23]. One patient in this study received biologic targeted therapy with telitacicept and ofatumumab during the disease course. Telitacicept has been dominantly allowed to treat systemic lupus erythematosus (SLE), myasthenia gravis (MG), rheumatoid arthritis (RA) and many kinds of kidney disease, and it’s the efficacy and safety in autoimmune diseases have been fully demonstrated in clinical practice [24]. Ofatumumab is a B-cell-targeting therapy and mostly used for multiple sclerosis (MS) [25]. But these two medicine have not been previously reported in the treatment of idiopathic myositis. In this study, due to suboptimal clinical response, this patient was subsequently transitioned to IVIG therapy. Sequential immunosuppressive therapy in this cohort consisted of low-dose glucocorticoids combined with an immunosuppressant. However, due to the limited sample size, no definitive conclusions can be drawn regarding the optimal combination regimen. Conclusion This study retrospectively analyzed the clinical features, therapeutic approaches, and outcomes of pediatric IMNM patients based on clinical presentations, laboratory findings, imaging, and muscle histopathology. However, this was a single-center, retrospective case series with a limited sample size and did not include an analysis of prognostic factors. Future research should prioritize multicenter, prospective, large-scale cohort studies to further delineate the clinical characteristics and prognostic determinants of pediatric IMNM, thereby supporting the development of evidence-based prognostic evaluation tools and individualized therapeutic strategies Abbreviations ASS Antisynthetase syndrome CK Creatine kinase DM Dermatomyositis DMD Duchenne muscular dystrophy EMG Electromyography ENMC The European Neuromuscular Centre HE Hematoxylin and eosin HMGCR Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase IBM Inclusion body myositis IIM Idiopathic inflammatory myopathy IMNM Immune-mediated necrotizing myopathy IVIG Intravenous immunoglobulin MAC Membrane attack complex MHC Major histocompatibility complex MMT Manual muscle testing MRI Magnetic resonance imaging mRS Modified Rankin Scale MSA Myositis-specific autoantibody NADH Nicotinamide adenine dinucleotide hydrogenase PM Polymyositis SRP Anti-signal recognition particle STIR Short-tau inversion recovery Declarations Acknowledgements Not applicable. Author’s contributions XYW and ZZW collected and analyzed data and wrote the manuscript. YXC, FH, LLM, LY, FY and JP validated and interpreted data. LFY and ZCL designed the study, supervised the process and critically revised the manuscript. All authors have read and approved the final manuscript. Funding The authors have no relevant financial or non-financial interests to disclose. Data availability All data generated or analyzed during this study are included in this published article. Ethics approval and consent to participate This study was approved by the Ethics Committee of Xiangya Hospital of Central South University and conducted in accordance with the ethical standards outlined in the Declaration of Helsinki. Written informed consent was obtained from the legal guardians of all participants. Consent for publication The parents of all the participants signed the Institutional Informed Consent for the participation and the anonymous use of their children’s clinical data for scientific purposes. Competing interests No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. References Oldroyd A, Lilleker J, Chinoy H. Idiopathic inflammatory myopathies - a guide to subtypes, diagnostic approach and treatment. Clin Med (Lond). 2017 Jul;17(4):322-328. Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, Vencovsky J, de Visser M, Hughes RA. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004 May;14(5):337-45. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7777355","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":529314262,"identity":"d9e7559a-8675-4883-ba72-35ff9c4e4a76","order_by":0,"name":"Yiwen Xu","email":"","orcid":"","institution":"Xiangya Hospital Central South University Department of Pediatrics","correspondingAuthor":false,"prefix":"","firstName":"Yiwen","middleName":"","lastName":"Xu","suffix":""},{"id":529314263,"identity":"a7c30504-64b6-4873-8454-44135afd7fb4","order_by":1,"name":"Zhanwei Zhang","email":"","orcid":"","institution":"Xiangya Hospital Central South 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maximus.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7777355/v1/189ef194cd4cc0e0bba11668.png"},{"id":94623077,"identity":"31308649-2d1a-4ab6-ae1f-5e4f08e5c70b","added_by":"auto","created_at":"2025-10-29 04:18:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":307469,"visible":true,"origin":"","legend":"\u003cp\u003e(a)\u003cstrong\u003e \u003c/strong\u003eThe Line Graph of edema and fatty infiltration mean scores. (b) The Line Graph of edema and fatty frequency.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7777355/v1/fe3c42430ef9a7df3e9b3b23.png"},{"id":94622968,"identity":"89854b76-53be-4f88-8d23-b75058c06a3b","added_by":"auto","created_at":"2025-10-29 04:18:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":937994,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative thigh MRI findings of muscle edema and fatty infiltration. (a, b) Muscle edema is shown on STIR imaging. (c, d) Muscle fatty infiltration is shown on T1-weighted imaging.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7777355/v1/73be4506a1ceef86e0806e84.png"},{"id":94622708,"identity":"a595f548-314f-405e-ac13-04761180ad3a","added_by":"auto","created_at":"2025-10-29 04:18:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3708858,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative muscle biopsy features of Case 2 with HMGCR antibody positivity. Hematoxylin and eosin staining (a). NADH dehydrogenase staining (b). Acid phosphatase staining (c). MHC-I expression (d). CD4-positive and CD8-positive lymphocytes, and CD68-positive macrophages in the endomysium (e, f, g). MAC immunohistochemical staining (h).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7777355/v1/ee4a0315975b3341d7112c43.png"},{"id":94623777,"identity":"17c8dfb7-1b3e-42fa-af7c-dad9e5000e5b","added_by":"auto","created_at":"2025-10-29 04:19:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7106336,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7777355/v1/bb37cfab-6673-4273-ae9b-ed6c2e287304.pdf"}],"financialInterests":"","formattedTitle":"Clinical Characteristics in Pediatric Patients with Immune-Mediated Necrotizing Myopathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIdiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune disorders characterized by chronic muscle inflammation and weakness. These conditions include dermatomyositis (DM), polymyositis (PM), antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). The principal clinical manifestations of IIMs encompass symmetric proximal muscle weakness, elevated serum muscle enzyme levels, presence of autoantibodies, and inflammatory cell infiltration in muscle histopathology. The disease exhibits two peak incidence periods: 45\u0026ndash;60 years and 5\u0026ndash;15 years, with a higher prevalence in adult [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. At the 119th international workshop of the European Neuromuscular Centre (ENMC), the sub-group of \u0026lsquo;IMNM\u0026rsquo; emerged as a separate entity among IIMs for the first time based on pathological criteria [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The characteristics of IMNM has some similarity with IIMs, but it progresses more rapidly. Among pediatric patients, the morbidity of IMNM is less than juvenile dermatomyositis (JDM) in juvenile IIMs. One previous research stated that pediatric IMNM accounts for just 2.9% in 440 juvenile IIMs, which is significantly lower than that in adults IMNM [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. With more and more acknowledge of IMNM, it is further subdivided into three subtypes based on the presence of myositis-specific autoantibodies (MSAs) according to the 2016 ENMC classification criteria: anti-signal recognition particle (SRP) antibody-positive, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive, and seronegative cases[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, comprehensive data on the clinical spectrum and outcomes of pediatric IMNM remain limited.\u003c/p\u003e\u003cp\u003eWhile substantial clinical data exist regarding adult IMNM, including its clinical features, treatment modalities, and prognostic factors, evidence on pediatric IMNM remains limited. This study presents a retrospective analysis of clinical data from 10 pediatric patients diagnosed with IMNM, aiming to describe the clinical manifestations, serological profiles, therapeutic strategies, and outcomes. The findings are intended to enhance clinical awareness of pediatric IMNM, facilitate early diagnosis, guide individualized treatment, and provide a foundation for future prospective research on this rare condition.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eDiagnostic\u0026nbsp;criteria and\u0026nbsp;patient\u0026nbsp;enrollment\u003c/p\u003e\n\u003cp\u003eClinical data were retrospectively collected and analyzed from pediatric patients diagnosed with IMNM at Xiangya Hospital between January 2016 and May 2025. The data encompassed clinical presentations, laboratory findings, treatment regimens, and outcomes. Cases meeting the established diagnostic criteria for IMNM were included, which consist of clinical features of myopathy, elevated creatine kinase levels, and seropositivity for specific autoantibodies\u0026nbsp;[4]. In addition, targeted genetic sequencing for common childhood-onset muscular dystrophies, including mutations in the DMD gene, was conducted to exclude inherited myopathies. Informed consent was obtained from all patients\u0026apos; legal guardians, and the study was approved by the Ethics Committee of Xiangya Hospital, conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eAntibodies\u0026nbsp;detection\u003c/p\u003e\n\u003cp\u003eSerum myositis autoantibodies were detected using Euroimmun immunoblot assays, following the manufacturer\u0026rsquo;s instructions as previously described\u0026nbsp;[5]. The panel included anti-Mi-2, anti-TIF1\u0026gamma;, anti-NXP2, anti-Ku, anti-PM-Scl75, anti-PM-Scl100, anti-SRP, anti-PL-7, anti-PL-12, anti-OJ, anti-cN-1A, anti-MDA5, anti-SAE1, anti-Jo-1, anti-EJ, anti-Ro-52, and anti-HMGCR antibodies. Immunoblot results were interpreted as weakly positive (+), positive (++), or strongly positive (+++) based on the intensity of the reaction bands.\u003c/p\u003e\n\u003cp\u003eMuscle\u0026nbsp;magnetic\u0026nbsp;resonance\u0026nbsp;imaging\u0026nbsp;parameters\u003c/p\u003e\n\u003cp\u003eMuscle magnetic resonance imaging (MRI) was performed using either a 1.5 Tesla or 3.0 Tesla scanner (Siemens, Erlangen, Germany) at Xiangya Hospital. The MRI protocol included coronal and axial T1-weighted, T2-weighted, and short-tau inversion recovery (STIR) sequences. Imaging parameters were as follows: T1-weighted\u0026mdash;repetition time (TR) 480 ms, echo time (TE) 13 ms, slice thickness 4 mm; T2-weighted\u0026mdash;TR 3280 ms, TE 65 ms, slice thickness 4 mm.\u003c/p\u003e\n\u003cp\u003eAssessment of muscular fatty infiltration and edema\u003c/p\u003e\n\u003cp\u003eThe degree of fatty infiltration was assessed on T1-weighted images based on a previously established classification system\u0026nbsp;[6], modified and categorized into six grades: 0, normal; 1, scattered signals; 2, mild abnormalities (\u0026lt;30% fatty infiltration); 3, moderate abnormalities (30\u0026ndash;60% fatty infiltration); 4, severe abnormalities (\u0026gt;60% fatty infiltration); 5, complete replacement of muscle tissue by fatty infiltration.\u003c/p\u003e\n\u003cp\u003eMuscle edema was graded based on STIR sequences using a six-point scale as follows\u0026nbsp;[7]: 0, normal; 1, scattered high signals without fusion; 2, slightly high scattered or small sheet-like signals involving less than 50% of the muscle; 3, higher scattered or small sheet-like signals involving less than 50%; 4, slightly high scattered or small sheet-like signals involving more than 50%; 5, higher scattered or small sheet-like signals involving more than 50%.\u003c/p\u003e\n\u003cp\u003eMuscle biopsy\u003c/p\u003e\n\u003cp\u003eMuscle biopsy specimens were obtained, frozen, sectioned, and fixed. Subsequently, they were stained with hematoxylin and eosin (HE) and immunostained with antibodies against C5b-9, CD4, CD8, CD20, CD68, major histocompatibility complex class I (MHC-I), and dystrophin (rod domain). Acid-fast staining techniques were employed to detect structural abnormalities in muscle biopsies. Nicotinamide adenine dinucleotide hydrogenase (NADH) staining was performed to evaluate mitochondrial enzyme activity and the internal architecture of muscle fibers\u0026nbsp;[8].\u003c/p\u003e\n\u003cp\u003eFollow up and outcome\u003c/p\u003e\n\u003cp\u003eFrom January 2016 to May 2025, a total of 10 patients were followed up. During the follow-up period, manual muscle testing (MMT) (Table 1) [9] and quality of life assessment using the modified Rankin Scale (mRS) (Table 2) [10, 11]were performed, with initial, best, and final mRS scores documented. Patients with cervical muscle involvement were classified as having axial muscle weakness, while the remaining patients were categorized as having limb muscle involvements.\u003c/p\u003e\n\u003cp\u003eTreatment outcomes were classified as complete remission, partial remission, or no significant improvement. Complete remission was defined as an mRS score of 0, partial remission as an mRS score of 1, and no significant improvement as an mRS score of 3 .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e The Manual Muscle Testing (MMT)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eNo contraction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eFlicker or trace of contraction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eActive movement with gravity eliminated\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eActive movement against gravity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eActive movement against gravity and resistance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eNormal power\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e The modified Rankin Scale (mRS)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003eRankin Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eNo symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eNo significant disability: despite symptoms able to carry out all usual duties and activities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eSlight disability: unable to perform all previous activities but able to look after own affairs without assistance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eModerate disability: requiring some help, but able to walk without assistance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eModerately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eSevere disability: bedridden, incontinent, and requiring constant nursing care and attention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eStatistical analysis\u003c/p\u003e\n\u003cp\u003eStatistical analysis was conducted using SPSS version 27.0 software. Normally distributed continuous variables were expressed as mean \u0026plusmn; standard deviation, whereas non-normally distributed data were presented as median (interquartile range).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eClinical features\u003c/p\u003e\n\u003cp\u003eTable 3 presents the clinical features of patients diagnosed with immune-mediated necrotizing myopathy (IMNM). A total of 10 patients were included, consisting of 6 females and 4 males. The median age at disease onset was 5.5 years (range: 3\u0026ndash;16). Myositis antibody testing revealed that 4 patients were positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody, while the remaining 6 were positive for anti-signal recognition particle (SRP) antibody. Overlapping myositis antibodies were detected in 2 patients with anti-HMGCR and 2 with anti-SRP antibodies. None of the IMNM patients with anti-HMGCR antibodies had prior statin exposure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll 10 patients presented with\u0026nbsp;both\u0026nbsp;upper and lower limb muscle weakness, while isolated lower limb involvement was observed in 1 patient. Axial muscle weakness was documented in 3 patients, manifesting as impaired neck flexion or rotation, weak shoulder shrugging, or abduction. Lower limb myalgia was reported in case 2 and case 6. No patient exhibited respiratory or cardiac symptoms. Gottron\u0026rsquo;s sign and periorbital rash were observed in 1 patient with anti-HMGCR and 4 patients with anti-SRP antibodies, respectively. Cutaneous manifestations in case 1 and case 5 occurred 10 and 18 months, respectively, prior to the onset of muscle weakness,\u0026nbsp;suggesting that these signs could serve as early indicators of IMNM. Case 1 was also diagnosed with subclinical hypothyroidism. No patient had coexisting rheumatic disease.\u003c/p\u003e\n\u003cp\u003eLaboratory data\u003c/p\u003e\n\u003cp\u003eThe median initial creatine kinase (CK) level was 3988.5 U/L (range:\u0026nbsp;2080\u0026ndash;13524 U/L; normal reference range: 50\u0026ndash;310 U/L). Elevated CK levels were detected in case 2 and case 4, 9 and 12 months before the onset of muscle weakness, respectively. The median peak and final CK levels were 10228 (range:\u0026nbsp;2080\u0026ndash;16674) U/L and 377.5 (range:\u0026nbsp;58\u0026ndash;2514) U/L, respectively. At the last follow-up, 5 patients had elevated CK levels, and among them, 4 remained asymptomatic or experienced only mild symptoms.\u003c/p\u003e\n\u003cp\u003eIn four HMGCR antibody-positive patients, the median initial, highest, and final CK levels were 6280.5 (range:\u0026nbsp;3270\u0026ndash;13524) U/L, 14324.5 (range:\u0026nbsp;10482\u0026ndash;16674) U/L, and 1537.5 (range:\u0026nbsp;589\u0026ndash;1778) U/L, respectively. In contrast, among five SRP antibody-positive patients, the corresponding values were 3171.5 (range:\u0026nbsp;2080\u0026ndash;11836) U/L, 7205.5 (range:\u0026nbsp;2080\u0026ndash;11836) U/L, and 102.5 (range:\u0026nbsp;58\u0026ndash;668) U/L, with two patients exhibiting peak CK levels at disease onset. These data indicate that CK levels in HMGCR antibody-positive patients were higher compared to those in SRP antibody-positive patients during disease progression, and that CK levels in SRP antibody-positive patients largely returned to normal by the end of the disease course\u0026nbsp;(Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e Clinical features of patients with IMNM\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eOnset of age, year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eAntibody\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eMuscle weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eLung disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eCardiac involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eSkin rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eInitial CK\u003c/p\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eHighest CK\u003c/p\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eLast CK\u003c/p\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eHMGCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eGottron sign in hands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e13524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e16485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e1297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eHMGCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003cp\u003ecervical muscle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e3270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e16674\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e2514\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eHMGCR, Mi-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003elower limbs, especially proximal\u003c/p\u003e\n \u003cp\u003ecervical muscle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e5804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e12164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e589\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eHMGCR, NXP2, PL-7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e6757\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e10482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e1778\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eSRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003ePeriorbital rash, Gottron sign in hands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e2080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e2080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eSRP, PM-Scl 75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e2870\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e9495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eSRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003cp\u003ecervical muscle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003ePeriorbital purple rash, Gottron sign in hands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e11836\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e11836\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e668\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eSRP, Ro-52, PM-Scl 75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e3136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e9974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eSRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003ePeriorbital rash, Gottron sign in hands and knees\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e3207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e4201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eCase 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003eSRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eupper and lower limbs, especially proximal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2821%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003ePeriorbital rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e4707\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.74359%;\"\u003e\n \u003cp\u003e4916\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.03419%;\"\u003e\n \u003cp\u003e166\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThigh MRI\u003c/p\u003e\n\u003cp\u003eAll patients underwent muscle magnetic resonance imaging (MRI). As shown in\u0026nbsp;Figure\u0026nbsp;1, thigh MRI revealed muscle edema in 8 of 10 patients, while fatty infiltration was observed in 5 patients\u0026nbsp;(Figure 1,\u0026nbsp;Figure 3). The frequency and mean scores of muscle edema were highest in the adductor magnus, whereas the gluteus maximus showed the highest mean scores and\u0026nbsp;frequency for fatty infiltration\u0026nbsp;(Figure 2,\u0026nbsp;Figure 3).\u003c/p\u003e\n\u003cp\u003eElectromyogram and myopathology\u003c/p\u003e\n\u003cp\u003eAmong the ten patients, eight underwent needle electromyography, which all demonstrated myogenic changes. Muscle biopsy results were available for only one HMGCR antibody-positive patient. The biopsy was taken from the left biceps brachii muscle. Hematoxylin and eosin staining revealed marked variation in myofiber size, scattered necrotic and regenerating myofibers, and moderate connective tissue proliferation. NADH dehydrogenase staining showed disruption of the intermyofibrillar network in most myofibers. Acid phosphatase staining demonstrated scattered focal increases in endomysial enzyme activity. No abnormalities were detected on Gomori staining, adenosine monophosphate (AMP) activity, succinate dehydrogenase staining, cytochrome C oxidase and succinate double staining, adenosine triphosphate (ATP) cyclase staining, or PAS and ORO staining. Immunohistochemical analysis for muscular dystrophy and inflammatory myopathy was also performed. In the muscular dystrophy panel, anti-dystrophin-R, -C, -N staining of dystrophin protein in muscle fiber membranes, anti-myosin-\u0026alpha;, -\u0026beta;, -\u0026gamma;, -\u0026delta; staining of myosin protein in the endomysium, and anti-dysferlin staining all showed normal expression. However, the inflammatory myopathy panel revealed characteristic findings: MHC-Ⅰ expression was positive in necrotic myofibers, with numerous CD4-positive lymphocytes, a few CD8-positive lymphocytes, and a few CD68-positive macrophages present in the endomysium, along with partial expression of the C5b-9 membrane attack complex (MAC) in the myofiber cytoplasm. No CD20-positive lymphocytes were observed. (Figure 4)\u003c/p\u003e\n\u003cp\u003eTreatment and outcome\u003c/p\u003e\n\u003cp\u003eAll pediatric patients received initial steroid therapy during follow-up until May 2025, including six patients treated with intravenous methylprednisolone pulse therapy and\u0026nbsp;four\u0026nbsp;patients receiving oral prednisone. The median duration of steroid maintenance therapy was 36.5 months (range: 9\u0026ndash;74 months). Additionally, these 10 patients received various forms of immunotherapy, including intravenous immunoglobulin (n=9), methotrexate (n=10), rituximab (n=7), mycophenolate mofetil (n=2), tacrolimus (n=2), azathioprine (n=1), telitacicept (n=1), and ofatumumab (n=1).\u003c/p\u003e\n\u003cp\u003eBased on the final modified Rankin Scale (mRS) score, five patients achieved complete remission (mRS=0), four patients showed partial remission (mRS=1), and one patient exhibited no significant remission (mRS=3). Among the five patients with complete remission, two achieved normalization of muscle strength and serum creatine kinase (CK) levels, along with antibody negativity, and were successfully weaned off medication. However, one patient experienced a relapse during the gradual tapering of therapy after achieving normal muscle strength, normal serum CK levels, and antibody negativity, as the signal recognition particle (SRP) antibody reappeared strongly positive (+++).\u0026nbsp;(Table 4,\u0026nbsp;Table 5)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eTreatment and outcome of Patients with IMNM\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eInitial steroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eTime of steroid maintenance, months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003eIntravenous immunoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eOther immunotherapies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003eInitial mRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003eBest mRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003eFinal mRS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e74 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 17 times. 1g/kg, once\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003e750mg/m2, twice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eHydroxychloroquine, azathioprine, methotrexate \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eOral prednisolone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 26 times. 1g/kg, once\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003e750mg/m2, once. 375mg/m2, twice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate, Mycophenolate mofetil \u003csup\u003ea\u003c/sup\u003e, tacrolimus,\u0026nbsp;telitacicept,\u0026nbsp;ofatumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e26 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 20 times. 1g/kg, monthly, twice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003e750mg/m2, twice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e34 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 15 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003e750mg/m2, three times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate \u003csup\u003ea\u003c/sup\u003e, tacrolimus \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e36 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, once\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, twice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003e750mg/m2, four times. 375mg/m2, six times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate, mycophenolate mofetil \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eOral prednisolone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e9 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 6 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eOral prednisolone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 6 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase\u0026nbsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003e2g/kg, monthly, 8 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.15451%;\"\u003e\n \u003cp\u003eCase 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003eOral prednisolone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.8784%;\"\u003e\n \u003cp\u003e71 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.4478%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1602%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.8841%;\"\u003e\n \u003cp\u003eMethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.72389%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.43634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003ea: Maintaining till last visit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e5\u003c/strong\u003e Treatment of IMNM Patients\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"274\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eTreatment methods\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003eTotal, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eMethylprednisolone pulse therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e6 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eOral prednisolone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e4 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eIntravenous immunoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e9 (90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eMethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e10 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e7 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eMycophenolate mofetil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e2 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e2 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eAzathioprine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e1 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eTelitacicept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e1 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eOfatumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e1 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 68.9781%;\"\u003e\n \u003cp\u003eHydroxychloroquine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.0219%;\"\u003e\n \u003cp\u003e1 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eApart from typical manifestation of IMNM, there are many atypical clinical features in disease progression, such as asymptomatic hyper CK level, limb-girdle muscular dystrophy-like phenotype, facioscapulohumeral muscular dystrophy-like phenotype and distal myopathy phenotype [12].\u0026nbsp;In this study,\u0026nbsp;we observed\u0026nbsp;all pediatric patients were hospitalized due to limb weakness, primarily presenting with proximal limb involvement, and three patients exhibited axial muscle weakness. Five patients had previously experienced other symptoms for at least one year before the onset of weakness, including elevated serum CK levels or rash\u0026nbsp;like DM\u0026rsquo;s,\u0026nbsp;which\u0026nbsp;were not recognized or appropriately addressed by their families. Therefore, rash and elevated serum CK levels may manifest early in pediatric IMNM patients; however, there is currently no statistical evidence supporting this observation, which warrants further confirmation through large cohort studies. Based on this finding, in children presenting with unexplained rash and elevated CK levels, even in the absence of weakness, testing for myositis-specific antibodies should be considered to facilitate early diagnosis.\u003c/p\u003e\n\u003cp\u003eExtra\u0026nbsp;muscular manifestations of IMNM in pediatric patients may include rash, heart failure, Raynaud\u0026rsquo;s phenomenon, interstitial lung disease, and malignancy. In our study, four patients exhibited periorbital rash, but none developed heart failure, Raynaud\u0026rsquo;s phenomenon, interstitial lung disease, or malignancy. Similarly, a previous retrospective cohort study from a single center in China involving 55 pediatric IMNM patients found no cases with Raynaud\u0026rsquo;s phenomenon, interstitial lung disease, or malignancy\u0026nbsp;[13]. Therefore, conducting a larger cohort study is necessary to determine the prevalence of extra\u0026nbsp;muscular manifestations among Chinese pediatric patients with IMNM.\u003c/p\u003e\n\u003cp\u003eMany studies demonstrated that statin medicine exposure associates with adult IMNM patients with\u0026nbsp;anti-HMGCR antibodies\u0026nbsp;positive [14, 15, 16]. Statins are widely used to treat dyslipidemia and reduce the risk of cardiovascular diseases, but there is no research reporting the pediatric IMNM exposing to statins. In the study, none of these patients have been exposed to statins, of which the reason may be dyslipidemia and cardiovascular diseases often occur in middle-people and elderly people.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe degree of muscle fat infiltration and edema in IMNM\u0026nbsp;is not synchronized. As the disease progresses, the degree of muscle edema gradually decreases, whereas fat infiltration remains stable or worsens. Previous literature lacks descriptions of MRI characteristics in the thigh muscles of\u0026nbsp;pediatric\u0026nbsp;IMNM. In patients with shorter disease duration, thigh muscle edema is the predominant lesion, while those with longer disease duration exhibit higher fat infiltration scores. However, fat infiltration can occur during the early stages of the disease. In this study, fat infiltration primarily affected the gluteus maximus, followed by the adductor magnus, with the most severe fat infiltration observed in the gluteus maximus. The most frequently involved muscle for edema in the thigh was the adductor magnus, followed by the gluteus maximus. This distribution corresponds with the clinical presentation of IMNM, which typically manifests as proximal limb weakness. Although MRI is only one component of the diagnostic criteria for IMNM in antibody-negative patients, clinicians routinely perform muscle MRI during the diagnostic process. This is because the extent of muscle fat infiltration or edema identified by MRI may serve as a marker reflecting disease severity\u0026nbsp;[17].\u003c/p\u003e\n\u003cp\u003eThe diagnostic criteria for IMNM proposed at the 224th International Symposium are categorized into antibody-positive and antibody-negative criteria\u0026nbsp;[4]. In the absence of specific autoantibodies, diagnosis requires integration of muscle pathology, electromyography, and muscle MRI findings. Due to the unique characteristics of pediatric patients, few underwent muscle biopsy, in contrast to adults. This study collected pathological results from only one pediatric case. Case 2 was initially suspected to have muscular dystrophy based on elevated creatine kinase (CK) levels and histopathological findings. However, the diagnosis of IMNM was confirmed after the development of muscle weakness and subsequent detection of muscle inflammation antibodies. This diagnostic challenge arises from overlapping histopathological features between IMNM and muscular dystrophy, leading to frequent misdiagnosis in the early stages. Previous cohort studies have also reported that pediatric IMNM can present with two types of muscle pathology: necrotizing myopathy and features mimicking muscular dystrophy, with the latter being more common[13]. Therefore, in patients presenting with elevated CK levels, testing for myositis-specific antibodies is essential for accurate diagnosis.\u003c/p\u003e\n\u003cp\u003eThe typical myopathological features of immune-mediated necrotizing myopathy (IMNM) include myofiber necrosis and regeneration, with or without inflammatory cell infiltration, which constitutes one of the pathological diagnostic criteria\u0026nbsp;[4]. However, these features are not specific to IMNM and can also be observed in other myopathies that involve myofiber necrosis. In addition to the evaluation of routine histological stains under light microscopy, immunohistochemical analysis is required for the diagnosis of antibody-negative IMNM. Currently, there is no consensus regarding the immunohistochemical characteristics of IMNM. A previous study evaluated the sensitivity and specificity of major histocompatibility complex (MHC) class Ⅰ and Ⅱ immunostaining in the diagnosis of idiopathic inflammatory myopathies (IIMs). The findings indicated that upregulation of MHC-Ⅰ expression may represent a nonspecific and common secondary response to muscle injury, whereas MHC-Ⅱ expression in IIM demonstrates high specificity with moderate sensitivity\u0026nbsp;[18]. Increased MHC-Ⅰ expression in muscle fibers is frequently observed in patients positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, supporting the immune-mediated pathogenesis of the disease, although it lacks specificity\u0026nbsp;[19]. In contrast, MHC-Ⅱ expression is rarely detected in IMNM and may serve as one of the exclusion criteria. Complement membrane attack complex (C5b-9) deposition is also commonly observed in patients with anti-HMGCR antibodies, but it may also be present in those with dermatomyositis (DM) and antisynthetase syndrome (ASS)\u0026nbsp;[20]. Although muscle biopsy remains the gold standard for diagnosing IMNM, its pathological features lack specificity. Therefore, a comprehensive diagnostic approach is necessary, incorporating clinical history, physical manifestations, serum creatine kinase (CK) levels, specific antibody testing, and muscle imaging findings.\u003c/p\u003e\n\u003cp\u003eTreatment of IMNM typically involves the administration of glucocorticoids, immunosuppressive agents, immunoglobulins, and biologic targeted therapies. According to the 2022 British Society for Rheumatology Guidelines for Juvenile IIM, high-dose glucocorticoids combined with methotrexate are recommended as first-line therapy for the majority of pediatric patients. Mycophenolate mofetil has demonstrated efficacy in improving both cutaneous and muscular manifestations, whereas intravenous immunoglobulin (IVIG), rituximab, and cyclophosphamide are primarily reserved for cases of severe or refractory IIM\u0026nbsp;[21]. In this study, all pediatric patients received either intravenous or oral glucocorticoids as initial treatment.\u0026nbsp;Oral glucocorticoid therapy plays a significant role in maintenance treatment.\u0026nbsp;Despite the use of minimal glucocorticoid doses\u0026nbsp;during following therapy,\u0026nbsp;it\u0026rsquo;s side effects cannot been ignored. For the children during the growth and development period the adverse reactions are more significant, with growth and development delay being the most serious [22]. Many parents expressed concern regarding the potential adverse effects of long-term glucocorticoid use on\u0026nbsp;this.\u0026nbsp;Future prospective studies are urgently needed to establish the minimal effective duration of glucocorticoid therapy in pediatric IMNM, aiming to balance efficacy with the minimization of long-term adverse effects on growth and development.\u003c/p\u003e\n\u003cp\u003eIn this study, two children got complete remission and drug discontinuance eventually. During the disease progression of patient 8, her CK level decreased to normal, and then started to reduce the dosage of prednisolone three months later, with addition to methotrexate gradually at the same time. Eight months later, she stopped use prednisolone because of the medicine deficiency by herself and her limbs power became worse latterly, relapse happening. However, after reusing the therapy of prednisolone and methotrexate, combining with IVIG for seven months, she started to decrease prednisolone when CK level was normal and antibodies were negative. Whereas, another patient started to reduce prednisolone gradually a month later after the CK level became normal and he did not experience a relapse. Comparing with these two patients\u0026rsquo; therapy tragedy, the latter received methylprednisolone pulse\u0026nbsp;and IVIG\u0026nbsp;therapy\u0026nbsp;at the early stage of the onset. A review favors early and aggressive immunotherapy therapy to minimize irreversible damage and fatty replacement of muscles, but these treatments are often not completely effective [23].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne patient in this study received biologic targeted therapy with telitacicept and ofatumumab during the disease course. Telitacicept has been dominantly allowed to treat systemic lupus erythematosus (SLE), myasthenia gravis (MG), rheumatoid arthritis (RA) and many kinds of kidney disease, and it\u0026rsquo;s the efficacy and safety in autoimmune diseases have been fully demonstrated in clinical practice [24]. Ofatumumab is a B-cell-targeting therapy and mostly used for multiple sclerosis (MS) [25]. But these two medicine have not been previously reported in the treatment of idiopathic myositis. In this study, due to suboptimal clinical response, this patient was subsequently transitioned to IVIG therapy. Sequential immunosuppressive therapy in this cohort consisted of low-dose glucocorticoids combined with an immunosuppressant. However, due to the limited sample size, no definitive conclusions can be drawn regarding the optimal combination regimen.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study retrospectively analyzed the clinical features, therapeutic approaches, and outcomes of pediatric IMNM patients based on clinical presentations, laboratory findings, imaging, and muscle histopathology. However, this was a single-center, retrospective case series with a limited sample size and did not include an analysis of prognostic factors. Future research should prioritize multicenter, prospective, large-scale cohort studies to further delineate the clinical characteristics and prognostic determinants of pediatric IMNM, thereby supporting the development of evidence-based prognostic evaluation tools and individualized therapeutic strategies\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASS\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Antisynthetase syndrome\u003c/p\u003e\n\u003cp\u003eCK\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Creatine kinase\u003c/p\u003e\n\u003cp\u003eDM\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Dermatomyositis\u003c/p\u003e\n\u003cp\u003eDMD Duchenne muscular dystrophy\u003c/p\u003e\n\u003cp\u003eEMG\u0026nbsp; \u0026nbsp;\u0026nbsp;Electromyography\u003c/p\u003e\n\u003cp\u003eENMC\u0026nbsp;\u0026nbsp;The European Neuromuscular Centre\u003c/p\u003e\n\u003cp\u003eHE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hematoxylin and eosin\u003c/p\u003e\n\u003cp\u003eHMGCR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase\u003c/p\u003e\n\u003cp\u003eIBM\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Inclusion body myositis\u003c/p\u003e\n\u003cp\u003eIIM\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Idiopathic inflammatory myopathy\u003c/p\u003e\n\u003cp\u003eIMNM\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Immune-mediated necrotizing myopathy\u003c/p\u003e\n\u003cp\u003eIVIG\u0026nbsp; \u0026nbsp; \u0026nbsp;Intravenous immunoglobulin\u003c/p\u003e\n\u003cp\u003eMAC Membrane attack complex\u003c/p\u003e\n\u003cp\u003eMHC\u0026nbsp; \u0026nbsp;\u0026nbsp;Major histocompatibility complex\u003c/p\u003e\n\u003cp\u003eMMT\u0026nbsp; \u0026nbsp;\u0026nbsp;Manual muscle testing\u003c/p\u003e\n\u003cp\u003eMRI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003emRS\u0026nbsp; \u0026nbsp; \u0026nbsp;Modified Rankin Scale\u003c/p\u003e\n\u003cp\u003eMSA\u0026nbsp; \u0026nbsp; \u0026nbsp;Myositis-specific autoantibody\u003c/p\u003e\n\u003cp\u003eNADH\u0026nbsp;\u0026nbsp;Nicotinamide adenine dinucleotide hydrogenase\u003c/p\u003e\n\u003cp\u003ePM\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Polymyositis\u003c/p\u003e\n\u003cp\u003eSRP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Anti-signal recognition particle\u003c/p\u003e\n\u003cp\u003eSTIR Short-tau inversion recovery\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXYW and ZZW collected and analyzed data and wrote the manuscript. YXC, FH, LLM, LY, FY and JP\u0026nbsp;validated and interpreted data. LFY and ZCL designed the study, supervised the process and critically revised the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Xiangya Hospital of Central South University and conducted in accordance with the ethical standards outlined in the Declaration of Helsinki. Written informed consent was obtained from the legal guardians of all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe parents of all the participants signed the Institutional Informed Consent for the participation and the anonymous use of their children\u0026rsquo;s clinical data for scientific purposes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eOldroyd A, Lilleker J, Chinoy H. Idiopathic inflammatory myopathies - a guide to subtypes, diagnostic approach and treatment. Clin Med (Lond). 2017 Jul;17(4):322-328.\u003c/li\u003e\n \u003cli\u003eHoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, Vencovsky J, de Visser M, Hughes RA. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004 May;14(5):337-45.\u003c/li\u003e\n \u003cli\u003eKishi T, Rider LG, Pak K, Barillas-Arias L, Henrickson M, McCarthy PL, Shaham B, Weiss PF, Horkayne-Szakaly I, Targoff IN, Miller FW, Mammen AL; Childhood Myositis Heterogeneity Study Group. Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients. 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Erratum in: Drugs. 2022 Jan;82(1):63.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Immune-mediated necrotizing myopathy, Children, Anti-SRP antibody, Anti-HMGCR antibody","lastPublishedDoi":"10.21203/rs.3.rs-7777355/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7777355/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective \u003c/strong\u003eTo investigate the clinical characteristics and therapeutic strategies of childhood immune-mediated necrotizing myopathy (IMNM) and to provide evidence for clinical diagnosis and management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e We retrospectively analyzedthe clinical data of 10 children diagnosed with IMNM at the Children's Medical Center, Xiangya Hospital, Central South University, from January 2016 to May 2025. The onset features, clinical manifestations, laboratory findings, muscle magnetic resonance imaging (MRI) characteristics, treatment modalities, and prognosis were summarized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003eAmong the 10 patients, 4 were male and 6 were female, with a median age at onset of 5.5 years (range: 3–16 years). The mainclinical manifestations included symmetric proximal muscle weakness (100%) and cutaneous manifestations(50%, including Gottron's sign and periorbital rash). Creatine kinase(CK) levels were markedly elevated, with a median of 3988.5 U/L (range: 2080–13524 U/L). Muscle MRI revealed edema or fatty infiltration in the thigh muscles. Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies were detected in 4 patients (40%), and anti-signal recognition particle(SRP) antibodies in 6 patients (60%). Electromyography (EMG) showed myopathic changes in all cases. Muscle histopathology demonstrated myofiber necrosis, regeneration, and inflammatory cell infiltration. All patients received glucocorticoid therapy, combined with oral methotrexate. Additionally, 5 patients were treated with rituximab, and 8 received intravenous immunoglobulin (IVIG). During follow-up, 4 patients achieved complete remission, 5 achieved partial remission, and 1 showed noclinical remission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003eChildhood IMNM is characterized by proximal muscle weakness, typical rash, and significantly elevated CK levels, frequently associated with anti-SRP or anti-HMGCR antibodies. Early immunosuppressive therapy, including glucocorticoids combined with immunosuppressants or IVIG, can significantly improve prognosis, emphasizingthe importance of early diagnosis and active intervention.\u003c/p\u003e","manuscriptTitle":"Clinical Characteristics in Pediatric Patients with Immune-Mediated Necrotizing Myopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 04:05:05","doi":"10.21203/rs.3.rs-7777355/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-12-06T08:59:54+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-11-07T15:56:09+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-14T08:24:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-10T13:34:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2025-10-10T02:10:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"27c19e3b-8702-47b0-a231-93a7bc813388","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-10T11:35:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-29 04:05:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7777355","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7777355","identity":"rs-7777355","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}