Immune-mediated necrotizing myopathy: Report of two cases.

BACKGROUND: Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase, with unique skeletal muscle pathology and magnetic resonance imaging features. CASE SUMMARY: In this paper, two patients are reported: One was positive for anti-signal recognition particle antibody, and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody. CONCLUSION: The clinical characteristics and treatment of the two patients were analysed, and the literature was reviewed to improve the recognition, diagnosis, and treatment of this disease.

A Child with Refractory and Relapsing Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Myopathy: Case-Based Review.

BACKGROUND/OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is rare in children. Here, we present a boy with relapsing refractory anti-HMGCR myopathy along with a systematic literature review. CASE REPORT: 17-year-old boy with five years of muscle weakness, rash, high creatinine kinase (CK) levels, and muscle biopsy compatible with inflammatory myopathy was diagnosed with juvenile dermatomyositis. He was treated with corticosteroids, intravenous immunoglobulin (IVIG), and methotrexate. His muscle weakness improved with this treatment although never completely resolved. CK levels decreased from ∼15000 U/L to ∼3000 U/L. At the age of 15, muscle weakness relapsed after an upper respiratory tract infection; pulse corticosteroid treatment was administered. The re-evaluated muscle biopsy showed a necrotizing pattern and the HMGCR antibody was positive confirming anti-HMGCR myopathy when he was 16. The diagnostic delay was 50 months. Disease activity was monitored by Medical Research Council score, MRI and functional tests. Despite corticosteroids, methotrexate, IVIG, cyclosporine A, and rituximab therapies, muscle weakness improved only slightly during the first three months and remained stable afterwards.Results of the Literature Search:We identified 16 articles describing 50 children (76% female) with anti-HMGCR myopathy by reviewing the English literature up to March 1st, 2022. Proximal muscle weakness was the most common clinical symptom (70.8%). Corticosteroids (84.8%), IVIG (58.7%), and methotrexate (56.5%) were preferred in most cases. Complete remission was achieved in nine patients (28.1%). CONCLUSION: Diagnosis and management of children with anti-HMGCR myopathy are challenging. Complete remission is achieved in only one third of these patients. Imaging biomarkers may aid treatment.

Becker Muscular Dystrophy Accompanied by Anti-HMGCR Antibody-positive Immune-mediated Necrotizing Myopathy.

Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease characterized by progressive muscle weakness that currently has no cure. Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune inflammatory myopathy characterized by proximal muscle weakness that is treated with immunosuppressive therapy. We herein report a patient diagnosed with BMD complicated with IMNM by a pathological analysis. Notably, the patient had an elevated serum anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody level. Oral glucocorticoid and methotrexate treatment partially improved the muscle weakness with decreased levels of serum creatine kinase. An accurate diagnosis is important for therapeutic decisions in these complicated cases.

Analysis of clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody-positive myopathy / 中华实用儿科临床杂志

Objective:To explore clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive myopathy.Methods:Two cases of pediatric anti-HMGCR antibody-positive myopathy admitted to the Department of Neurology, Shenzhen Children′s Hospital from January to July 2020 were retrospectively analyzed for their clinical manifestations, creatine kinase (CK), myositis autoantibody, electromyography (EMG), muscle pathology, muscle magnetic resonance imaging (MRI), and treatment information.Results:Both of them were female cases.Case 1 was 3 years and 11 months old and case 2 was 7 years and 9 months old.They used to be healthy without history of statin use.Case 1 showed chronic onset of the disease, and case 2 had a subacute onset.The main clinical manifestations were progressive symmetric proximal muscle weakness accompanied by myalgia.Case 1 developed skin rash but case 2 did not.Significantly increased CK level was detected in both of them, which increased by 27.3-48.0 and 66.7-77.4 times of the upper limit before treatment in case 1 and case 2, respectively.They were diagnosed as muscular dystrophy at the early stage.EMG results suggested myogenic injuries in 2 cases, and muscle MRI showed extensive muscle edema.The muscle pathology of the 2 cases suggested muscle necrosis with a small amount of inflammatory cell infiltration.After diagnosis, both of them were treated with Methylprednisolone combined with intravenous immunoglobulin.CK decreased significantly but remained high, and muscle weakness was improved but did not return to normal.Oral Prednisone was given after discharge and case 2 was additionally medicated with azathioprine.Conclusions:Compared with adult patients, the clinical characteristics of pediatric anti-HMGCR antibody-positive myopathy are mostly similar.However, children patients usually have no history of statins and are more difficult to treat, less effective and worse prognosis.In addition, children patients are more likely to be diagnosed with " muscular dystrophy" at the beginning of illness.Therefore, idiopathic myositis autoantibody should be examined to confirm the diagnosis for children suspected to be " muscular dystrophy" but not confirmed by genetic examination.

Treatment experience of Taiwanese patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy.

Immune-mediated necrotizing myopathy (IMNM) has emerged as a new subgroup of idiopathic inflammatory myopathy in the past decade, associated with the presence of two autoantibodies against signal recognition particle and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We aim to analyze the clinical, pathological, and imaging phenotypes of the patients with anti-HMGCR myopathy in our cohort. Five patients with anti-HMGCR myopathy have been enrolled who were all female; three were pediatric and two were adult patients. The muscle pathology of patients met the diagnostic criteria of IMNM. On muscle magnetic resonance imaging, adductors were earliest affected while lower legs were relatively preserved with highest degree of involvement in medial head of gastrocnemius. In upper extremities, biceps brachii was the most severely involved, followed by triceps. All patients were refractory to steroid mono-therapy. For pediatric patients, all three patients eventually became responsive to steroid with either intravenous immunoglobulin or rituximab despite variable motor function recovered at present due to different intervention timing. For adult patients, one with statin exposure responded well to steroid and azathioprine use and the motor function returned to the baseline. The other adult patient finally got stabilized and slowly improved with steroid and methotrexate 13 years after the start of therapy. The creatine kinase (CK) levels of all patients were decreased along with clinical severity. In conclusion, muscle imaging might be of help for the diagnosis. Treatment with immuno-suppressants could be considered together with steroid from the beginning.

Rituximab in the Treatment of Refractory Anti-HMGCR Immune-mediated Necrotizing Myopathy.

OBJECTIVE: A pathogenic role of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies has been proposed. Our objective was to assess efficacy of rituximab (RTX) in anti-HMGCR immune-mediated necrotizing myopathy. METHODS: All patients who had been treated with RTX were retrospectively reviewed to assess features and outcome. RESULTS: Three of 9 patients demonstrated stable or improved muscle strength ± decline in creatine kinase levels, or T2/short-tau inversion recovery hypersignal decrease on magnetic resonance imaging following RTX treatment. RTX permitted intravenous immunoglobulin discontinuation and corticosteroid reduction to low dose in 2 patients. CONCLUSION: One-third of patients with refractory anti-HMGCR had improved strength or other evidence of improved disease activity following RTX treatment.

A case report of autoimmune necrotizing myositis presenting as dysphagia and neck swelling.

BACKGROUND: Severe dysphagia may occur in the immune mediated necrotizing myopathies (IMNM). Neck swelling and severe dysphagia as the initial symptoms upon presentation has not been previously described. CASE PRESENTATION: A 55-year-old male with a 4 week history of neck swelling, fatigue, dysphagia, myalgias, night sweats, and cough was admitted for an elevated CK. He underwent extensive infectious and inflammatory evaluation including neck imaging and muscle biopsy. Neck CT and MRI showed inflammation throughout his strap muscles, retropharyngeal soft tissues and deltoids. Infectious work up was negative. Deltoid muscle biopsy demonstrated evidence of IMNM. Lab tests revealed anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies confirming the diagnosis of HMGCR IMNM. CONCLUSIONS: HMGCR IMNM is a rare and incompletely understood disease process. Awareness of HMGCR IMNM could potentially lead to earlier diagnosis, treatment and improved clinical outcomes as disease progression can be rapid and severe.

Increasing incidence of immune-mediated necrotizing myopathy: single-centre experience.

OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) is characterized by the predominant presence of necrotic muscle fibres in muscle biopsy and variable response to immunosuppressive treatment. The aims of this study were to analyse the temporal trend of IMNM incidence in our centre over the past 10 years and to explore the role of statins as possible causative agents. METHODS: A retrospective evaluation of muscle biopsy results, clinical and laboratory data, including antibody associations of all patients with idiopathic inflammatory myopathy newly diagnosed between 2004 and June 2014, was performed. Available sera were tested for the presence of anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) autoantibodies. RESULTS: Of 357 biopsied patients, 233 fulfilled criteria for inflammatory/immune-mediated myopathy, including 27 (11.6%) classified as IMNM. There were no patients with IMNM diagnosed between 2004 and 2007; subsequently, two to three cases of IMNM per year were seen during the period 2008-11, with a substantial increase to 18 cases (66.6% of all IMNM biopsies) in 2012-14. Thirteen of 27 patients (48%) had a history of statin use, 11 (85%) of whom had positive anti-HMGCR antibodies. There was no IMNM patient without a history of statin use who was anti-HMGCR antibody positive. CONCLUSION: Our data show an increasing incidence of IMNM, which is mainly accounted for by anti-HMGCR-positive IMNM associated with the use of statins.