Juvenile dermatomyositis with central nervous system involvement: two case reports from a retrospective single-center cohort, with literature review.

Background: Juvenile dermatomyositis (JDM) is a systemic autoimmune disease primarily involving the muscles and skin; it can also affect the central nervous system (CNS). The relevant literature provides limited information regarding the characteristics of JDM with CNS involvement. Method: We reviewed patients with JDM who were hospitalized at our center between January 2016 and August 2023, with a focus on those with CNS involvement. The aim was to provide detailed case reports on these patients, and to summarize the relevant literature about the characteristics of similar cases. Results: Among 193 hospitalized patients with JDM, two (1.03%) had CNS involvement. Two patients, a 5.5-year-old girl and an 11-year-old boy, were admitted with severe proximal muscle weakness and seizures, and presented with active cutaneous vasculitis. Both were ultimately diagnosed with JDM, with CNS involvement. Both patients had confirmed presence of anti-NXP2 antibody through myositis-specific antibody analysis. Additionally, they all exhibited hyperferritinemia and thrombocytopenia. Salvage therapies like intravenous methylprednisolone (IVMP) pulse therapy and/or plasma exchange were administered successfully. At final follow-up, both patients had achieved complete clinical response and full neurological recovery. Our literature review identified nine similar case studies. CNS involvement usually occurred within the first 10 months of the disease course, and most of these patients had fatal outcomes, with a mortality rate of 66.6% (6/9). Including the two patients described herein, the median age for disease onset is 10.5 years (range 4-17 years), and the male: female ratio is 6:5. Seizures are the most common neurological symptom, accompanied by active cutaneous vasculitis. The brain biopsies showed two distinct pathological presentations: one was central nervous system vasculitis, and the other was cerebral macrophage activation syndrome. Conclusions: CNS involvement is a rare but life-threatening JDM complication. Herein, our cases and the literature indicate that it typically occurs within the first 10 months of the disease course and manifests as seizures, often accompanied by active cutaneous vasculitis, with fatal outcomes. Timely implementation of salvage therapies, like IVMP pulse therapy and plasma exchange, may significantly impact patient outcomes.

Clinical profile of anti-NXP-2 antibody-positive inflammatory myositis and outcome in an Indian population.

INTRODUCTION: Myositis-specific antibodies (MSA) play an important role in the clinical presentation and prognosis of patients with idiopathic inflammatory myositis (IIM). Anti-NXP-2 is one of the newly described MSA. OBJECTIVE: We aimed to describe various clinical presentations associated with anti-NXP2 antibodies and assess response to treatment. METHODS: In this retrospective study, the electronic medical records of all patients who tested positive for anti-NXP2 during June 2019 to April 2022 were screened. Details of demography, clinical presentation, and treatment data were recorded. The anti-NXP2 was tested using the Euro line test kit. Any patient who had an intensity of ≥1+ was considered testing positive. The diagnosis of IIM was reviewed after applying the 2017 European League of Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria of myositis. RESULTS: Among the 660 suspected patients, 470 (71.2%) patients were positive for IIM, and 28 (5.95%) patients were positive for anti-NXP2. From anti-NXP2-antibody positive, 21/470 (4.46%) patients fulfilled criteria for IIM. Among 12 adult (57.14%) patients with IIM, 7 (58.33%) presented as polymyositis (PM) and 5 (41.6%) as dermatomyositis (DM) with median age at presentation of 45 (IQR: 25-58) years. Calcinosis and subcutaneous oedema were observed in 4 (19%) and 2 (9.52%), respectively; myalgia in 6 (28.6%); and distal muscle weakness in 5 (23.8%) patients. Malignancy at the time of diagnosis was observed in two adults with IIM (16.7%), one with DM (intraductal breast cancer), and another with PM (anaplastic large cell lymphoma). Remaining, 9 had juvenile dermatomyositis (JDM) with a median age of 4 (IQR: 3-8) years. Seven (77.8%) patients with JDM had skin rash specific for DM (heliotrope rash and Gottron's papule). None of the patients had cardiac and lung involvement, while GI symptoms, especially dysphagia, were present in 5 (23.8%) patients. During a median follow-up of 19 months (IQR: 12-26 months), 19/19 patients reported improvement and were in remission with treatment. CONCLUSION: The current study shows that adult DM patients with anti-NXP-2 autoantibodies have a unique clinical phenotype. Its presentation differs between adult and JDM, even in different parts of the world. Muscle weakness is mild and responds to treatment. Dysphagia needs more time and aggressive IS for improvement as compared to other muscle involvement. Key Points • Anti-NXP-2 antibody presentation varied from adult to child, as in different parts of the world. • In Indian adult patients, non-specific skin manifestations were more common, whereas in JDM, specific skin features were common. • There was less likely involvement of the lung and heart. But more risk of GI involvement requiring aggressive management. • Adult with anti-NXP-2 antibody should be screened for malignancy at the time of presentation.

Anti-nuclear matrix protein 2 antibody-positive dermatomyositis with gastrointestinal ulcers: A case report.

Gastrointestinal manifestations are a very rare complication of dermatomyositis (DM) and are much less frequent in adult cases than in juvenile cases. Only a few previous papers have reported adult patients who had DM with anti-nuclear matrix protein 2 (anti-NXP2) antibodies and who developed gastrointestinal ulcers. Herein, we report a similar case of a 50-year-old man who had DM with anti-NXP2 antibodies followed by relapsing multiple gastrointestinal ulcers. Even after the administration of prednisolone, his muscle weakness and myalgia deteriorated and gastrointestinal ulcers relapsed. In contrast, intravenous immunoglobulin and azathioprine improved his muscle weakness and gastrointestinal ulcers. Based on the parallel disease activity of the muscular and gastrointestinal symptoms, we considered that his gastrointestinal ulcers were a complication of DM with anti-NXP2 antibodies. We also propose that early intensive immunosuppressive therapy would be required for the muscular and gastrointestinal symptoms in DM with anti-NXP2 antibodies.

Clinical value of cancer-associated myositis-specific antibodies, anti-transcriptional intermediary factor 1-γ, and anti-nuclear matrix protein 2 antibodies in a retrospective cohort of dermatomyositis/polymyositis in a Japanese community hospital.

Among the myositis-specific antibodies (MSA), anti-transcriptional intermediary factor 1 (TIF1)-γ and anti-nuclear matrix protein 2 (NXP2) antibodies are reportedly associated with cancer-associated myositis (CAM). We aimed to investigate patient characteristics of CAM and the clinical role of cancer-associated MSA (caMSA) in a retrospective cohort from a city hospital. All patients visiting our department between April 2014 and October 2021 with newly diagnosed dermatomyositis, polymyositis, and clinically amyopathic dermatomyositis were included. Anti-TIF1-γ and anti-NXP2 antibodies were collectively considered as caMSA. First, we compared clinical characteristics in CAM, defined as cases showing onset or recurrence of malignancy within 5 years, versus non-CAM. Second, we investigated independent risk factors for CAM. Third, we compared clinical characteristics with and without caMSA within CAM. Finally, we investigated whether caMSA was predictive of poor prognosis. The cohort of 39 patients included 12 (30.7%) CAM cases. Compared with non-CAM, CAM had significantly more dermatomyositis and higher frequencies of dysphagia, anti-TIF1-γ antibody, and caMSA. Using logistic regression analysis, caMSA was an independent risk factor for CAM. In a comparison between caMSA and non-caMSA within CAM, caMSA was associated with higher frequencies of stage ≥ II. However, caMSA did not necessarily indicate a poor prognosis. Only caMSA represented an independent risk factor for CAM and showed a significant association with advanced cancer. Key Points • Cancer-associated MSA was an independent risk factor for cancer-associated myositis. • Cancer-associated MSA was associated with advanced cancer.

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Juvenile dermatomyositis (JDM) is an autoimmune disease manifesting as proximal muscle weakness and skin rash and can involve multiple systems and visceral organs. Myositis-specific autoantibodies (MSAs) are highly associated with various complications and prognosis in JDM. Patients with anti-Mi-2 antibodies tend to have good prognosis and typical clinical symptoms. Patients with anti-MDA5 antibodies often have diffuse interstitial lung disease and skin ulcer, with mild symptoms of myositis. Patients with anti-NXP2 antibodies often have calcinosis, and such antibodies are associated with gastrointestinal bleeding and perforation. Patients with anti-TIF1-γ antibodies have diffuse and refractory skin lesions. Anti-SAE antibodies are rarely detected in children, with few reports of such cases. This article reviews the features of clinical phenotypes in JDM children with these five types of MSAs, so as to provide a basis for the clinical treatment and follow-up management of children with JDM.

[A case of dermatomyositis positive for anti-nuclear matrix protein 2 antibody without dermatologic symptoms].

We report a 47-year-old woman who presented with progressive myalgia, weakness in the proximal limbs, and dysphagia for a month and a half. No skin rash was observed on admission. Examination of MRI data suggested inflammatory changes in the proximal limbs and trunk muscles. Biopsy specimens from the left biceps muscle showed no perifascicular atrophy, but immunohistochemical staining revealed the presence of myxovirus resistance protein A (MxA) in myofibers, strongly suggesting dermatomyositis (DM). In addition, her serum was positive for anti-nuclear matrix protein 2 (anti-NXP-2) antibody, which is reportedly useful as a marker of DM without skin lesions. Her symptoms gradually improved upon intravenous methylprednisolone pulse therapy in conjunction with oral prednisolone, oral tacrolimus, and intravenous immunoglobulin therapy. Our findings suggest that in cases where inflammatory muscle disease is suspected, anti-NXP-2 antibody analyses should be considered for precise diagnosis, even if there are no dermatological symptoms.

Clinical impact of myositis-specific autoantibodies on long-term prognosis of juvenile idiopathic inflammatory myopathies: multicentre study.

OBJECTIVES: This study aimed to investigate the clinical characteristics, treatment and prognosis of juvenile idiopathic inflammatory myopathies (JIIM) in Japan for each myositis-specific autoantibody (MSA) profile. METHODS: A multicentre, retrospective study was conducted using data of patients with JIIM at nine paediatric rheumatology centres in Japan. Patients with MSA profiles, determined by immunoprecipitation using stored serum from the active stage, were included. RESULTS: MSA were detected in 85 of 96 cases eligible for the analyses. Over 90% of the patients in this study had one of the following three MSA types: anti-melanoma differentiation-associated protein 5 (MDA5) (n = 31), anti-transcriptional intermediary factor 1 alpha and/or gamma subunits (TIF1γ) (n = 25) and anti-nuclear matrix protein 2 (NXP2) (n = 25) antibodies. Gottron papules and periungual capillary abnormalities were the most common signs of every MSA group in the initial phase. The presence of interstitial lung disease (ILD) was the highest risk factor for patients with anti-MDA5 antibodies. Most patients were administered multiple drug therapies: glucocorticoids and MTX were administered to patients with anti-TIF1γ or anti-NXP2 antibodies. Half of the patients with anti-MDA5 antibodies received more than three medications including i.v. CYC, especially patients with ILD. Patients with anti-MDA5 antibodies were more likely to achieve drug-free remission (29 vs 21%) and less likely to relapse (26 vs 44%) than others. CONCLUSION: Anti-MDA5 antibodies are the most common MSA type in Japan, and patients with this antibody are characterized by ILD at onset, multiple medications including i.v. CYC, drug-free remission, and a lower frequency of relapse. New therapeutic strategies are required for other MSA types.

Gastrointestinal perforation in anti-NXP2 antibody-associated juvenile dermatomyositis: case reports and a review of the literature.

BACKGROUND: To summarize the characteristics of gastrointestinal (GI) perforation in anti-nuclear matrix protein 2 (NXP2) antibody-associated juvenile dermatomyositis (JDM). METHODS: Five patients with GI perforation from a JDM cohort of 120 cases are described. Relevant literature was reviewed. RESULTS: Five patients, including four females and one male, were included in the study. The age of onset of these patients ranged from 3.3 to 9.5 years with the median age of 5.0 years. When these patients were complicated by GI perforation, childhood myositis assessment score (CMAS) ranged from 1 to 5 with the median score of 2. Myositis-specific antibody (MSA) spectrum analysis indicated that the five patients were anti-NXP2 antibody positive. The initial symptoms of GI perforation were progressive abdominal pain and intermittent fever. Two patients also presented with ureteral calculus with hydronephrosis and ureteral stricture. Surgery was performed in four patients. One patient failed to undergo a repair as the perforation was high in position. For the other three patients, perforation repair was successful, of which two patients failed due to recurrent perforation. At 24 months postoperative follow-up, one patient was in complete remission on prednisone (Pred) and methotrexate (MTX) treatment, and her ureteral stricture had disappeared. The other four patients died. Adding these cases with 16 other patients described in the literature, the symptom at onset was progressive abdominal pain, which often occurred within 10 months after JDM was diagnosed. Perforation most commonly occurred in the duodenum, although it also occurred at multiple sites or was recurrent. The mortality rate of GI perforation in JDM was 38% (8/21). CONCLUSIONS: All the five perforation cases in our study subjected to MSA analysis were anti-NXP2 antibody positive. The symptom at onset was abdominal pain. The most common site of perforation was the duodenum in the retroperitoneum, and the lack of acute abdominal manifestations prevented early diagnosis. GI perforation may be a fatal complication in JDM, and early diagnosis is very important. More research is needed to determine the pathogenesis and predictive factors of GI perforation in JDM.

Recent research on myositis-specific autoantibodies in juvenile dermatomyositis / 中国当代儿科杂志

Juvenile dermatomyositis (JDM) is an autoimmune disease manifesting as proximal muscle weakness and skin rash and can involve multiple systems and visceral organs. Myositis-specific autoantibodies (MSAs) are highly associated with various complications and prognosis in JDM. Patients with anti-Mi-2 antibodies tend to have good prognosis and typical clinical symptoms. Patients with anti-MDA5 antibodies often have diffuse interstitial lung disease and skin ulcer, with mild symptoms of myositis. Patients with anti-NXP2 antibodies often have calcinosis, and such antibodies are associated with gastrointestinal bleeding and perforation. Patients with anti-TIF1-γ antibodies have diffuse and refractory skin lesions. Anti-SAE antibodies are rarely detected in children, with few reports of such cases. This article reviews the features of clinical phenotypes in JDM children with these five types of MSAs, so as to provide a basis for the clinical treatment and follow-up management of children with JDM.