Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis

Abhijith Paladugula; Ashley Blaske

Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis

Abhijith Paladugula
, Ashley Blaske

Department of Internal Medicine

East Tennessee State University

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis Introduction: Immune-mediated necrotizing myositis (IMNM) is a subset of idiopathic inflammatory myopathies (IIMs), characterized by chronic muscle inflammation and involvement of other organ systems, displaying diverse clinical presentations. While the exact cause remains unknown, these conditions have been linked to factors such as malignancy, exposure to medications, or toxins. Within the IMNM category, a particular subtype is associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myositis-specific autoantibodies (1). In about 67% of cases, this antibody is correlated with prior statin usage (2); although studies suggest a lesser association with statins in certain cases (3). Instances of anti-HMGCR-positive IMNM have been documented in pediatric and young adult populations who have never been exposed to statin medications (4). Case presentation: A 27-year-old man with a history of childhood seizures, but no current medication usage presented with progressive proximal muscle weakness over a two-month period, resulting in falls and requiring wheelchair assistance for mobility. Initial laboratory findings revealed elevated levels of Creatine kinase, aldolase, and transaminases. Muscle biopsy showed scattered regenerating and necrotic muscle fibers with limited chronic lymphoid inflammation consistent with necrotizing myopathy. Positive HMGCR autoantibodies were detected, and other myositis antibody tests were negative. He had never used statin medication. Initial treatment includes corticosteroids, IVIG infusions, and physical therapy. The patient is being followed closely. Discussion: Patients with anti-HMGCR myopathy primarily exhibit skeletal muscle involvement, often without affecting other organs. Consequently, myositis may sometimes be misdiagnosed as muscular dystrophy, particularly in younger individuals. A comprehensive evaluation by healthcare providers is crucial for distinguishing between these conditions. Notably, some cases of anti-HMGCR-positive IMNM may involve diet as a source of statin exposure, as statins are present in red yeast rice and specific mushroom species like Pleurotus spp. and Agaricus bisporus (3,5). Managing anti-HMGCR-positive IMNM poses challenges due to its rarity and the limited availability of clinical trials. Treatment options include corticosteroids, methotrexate, rituximab, and/or IVIG (6). Alternative therapies such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, or cyclophosphamide may also be considered. Additionally, physical therapy plays a crucial role in optimizing function and improving quality of life (7). A longitudinal study has indicated that younger patients often experience more severe disease and a poorer prognosis compared to older patients (8). References: 1. Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, Mammen AL, Miller FW. Idiopathic inflammatory myopathies. Nat Rev Dis Primers. 2021 Dec 2;7(1):86. doi: 10.1038/s41572-021-00321-x. PMID: 34857798. 2. Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011 Mar;63(3):713-21. doi: 10.1002/art.30156. PMID: 21360500; PMCID: PMC3335400. 3. Szczesny, Piotr, et al. "Screening for anti-HMGCR antibodies in a large single myositis center reveals infrequent exposure to statins and diversiform presentation of the disease." Frontiers in Immunology 13 (2022): 866701. 4. Kishi T, Rider LG, Pak K, et al. Association of anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibodies with DRB1*07:01 and severe myositis in juvenile myositis patients. Arthritis Care Res (Hoboken) 2017;69:1088–1094. 5. Barbacki, Ariane, et al. "Immune-Mediated Necrotizing Myopathy and dietary sources of statins." Annals of Internal Medicine 168.12 (2018): 893-904. 6. Meyer, A., Troyanov, Y., Drouin, J. et al. Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients. Arthritis Res Ther 22, 5 (2020). https://doi.org/10.1186/s13075-019-2093-6 7. Alexanderson H. Exercise in Myositis. Curr Treatm Opt Rheumatol. 2018;4(4):289-298. doi: 10.1007/s40674-018-0113-3. Epub 2018 Nov 23. PMID: 30613464; PMCID: PMC6299050. 8. Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, Parks CA, Casciola-Rosen L, Christopher-Stine L, Mammen AL. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017 May 1;56(5):787-794. doi: 10.1093/rheumatology/kew470. PMID: 28096458; PMCID: PMC5850825.

Original language	American English
Title of host publication	Congress of Clinical Rheumatology
State	Published - May 2024

Cite this

@inproceedings{373480c836aa4342a4aaffd8b2129e66,

title = "Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis",

abstract = "Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis Introduction: Immune-mediated necrotizing myositis (IMNM) is a subset of idiopathic inflammatory myopathies (IIMs), characterized by chronic muscle inflammation and involvement of other organ systems, displaying diverse clinical presentations. While the exact cause remains unknown, these conditions have been linked to factors such as malignancy, exposure to medications, or toxins. Within the IMNM category, a particular subtype is associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myositis-specific autoantibodies (1). In about 67\% of cases, this antibody is correlated with prior statin usage (2); although studies suggest a lesser association with statins in certain cases (3). Instances of anti-HMGCR-positive IMNM have been documented in pediatric and young adult populations who have never been exposed to statin medications (4). Case presentation: A 27-year-old man with a history of childhood seizures, but no current medication usage presented with progressive proximal muscle weakness over a two-month period, resulting in falls and requiring wheelchair assistance for mobility. Initial laboratory findings revealed elevated levels of Creatine kinase, aldolase, and transaminases. Muscle biopsy showed scattered regenerating and necrotic muscle fibers with limited chronic lymphoid inflammation consistent with necrotizing myopathy. Positive HMGCR autoantibodies were detected, and other myositis antibody tests were negative. He had never used statin medication. Initial treatment includes corticosteroids, IVIG infusions, and physical therapy. The patient is being followed closely. Discussion: Patients with anti-HMGCR myopathy primarily exhibit skeletal muscle involvement, often without affecting other organs. Consequently, myositis may sometimes be misdiagnosed as muscular dystrophy, particularly in younger individuals. A comprehensive evaluation by healthcare providers is crucial for distinguishing between these conditions. Notably, some cases of anti-HMGCR-positive IMNM may involve diet as a source of statin exposure, as statins are present in red yeast rice and specific mushroom species like Pleurotus spp. and Agaricus bisporus (3,5). Managing anti-HMGCR-positive IMNM poses challenges due to its rarity and the limited availability of clinical trials. Treatment options include corticosteroids, methotrexate, rituximab, and/or IVIG (6). Alternative therapies such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, or cyclophosphamide may also be considered. Additionally, physical therapy plays a crucial role in optimizing function and improving quality of life (7). A longitudinal study has indicated that younger patients often experience more severe disease and a poorer prognosis compared to older patients (8). References: 1. Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, Mammen AL, Miller FW. Idiopathic inflammatory myopathies. Nat Rev Dis Primers. 2021 Dec 2;7(1):86. doi: 10.1038/s41572-021-00321-x. PMID: 34857798. 2. Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011 Mar;63(3):713-21. doi: 10.1002/art.30156. PMID: 21360500; PMCID: PMC3335400. 3. Szczesny, Piotr, et al. {"}Screening for anti-HMGCR antibodies in a large single myositis center reveals infrequent exposure to statins and diversiform presentation of the disease.{"} Frontiers in Immunology 13 (2022): 866701. 4. Kishi T, Rider LG, Pak K, et al. Association of anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibodies with DRB1*07:01 and severe myositis in juvenile myositis patients. Arthritis Care Res (Hoboken) 2017;69:1088–1094. 5. Barbacki, Ariane, et al. {"}Immune-Mediated Necrotizing Myopathy and dietary sources of statins.{"} Annals of Internal Medicine 168.12 (2018): 893-904. 6. Meyer, A., Troyanov, Y., Drouin, J. et al. Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients. Arthritis Res Ther 22, 5 (2020). https://doi.org/10.1186/s13075-019-2093-6 7. Alexanderson H. Exercise in Myositis. Curr Treatm Opt Rheumatol. 2018;4(4):289-298. doi: 10.1007/s40674-018-0113-3. Epub 2018 Nov 23. PMID: 30613464; PMCID: PMC6299050. 8. Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, Parks CA, Casciola-Rosen L, Christopher-Stine L, Mammen AL. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017 May 1;56(5):787-794. doi: 10.1093/rheumatology/kew470. PMID: 28096458; PMCID: PMC5850825.",

author = "Abhijith Paladugula and Ashley Blaske",

year = "2024",

month = may,

language = "American English",

booktitle = "Congress of Clinical Rheumatology",

}

TY - GEN

T1 - Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis

AU - Paladugula, Abhijith

AU - Blaske, Ashley

PY - 2024/5

Y1 - 2024/5

N2 - Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis Introduction: Immune-mediated necrotizing myositis (IMNM) is a subset of idiopathic inflammatory myopathies (IIMs), characterized by chronic muscle inflammation and involvement of other organ systems, displaying diverse clinical presentations. While the exact cause remains unknown, these conditions have been linked to factors such as malignancy, exposure to medications, or toxins. Within the IMNM category, a particular subtype is associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myositis-specific autoantibodies (1). In about 67% of cases, this antibody is correlated with prior statin usage (2); although studies suggest a lesser association with statins in certain cases (3). Instances of anti-HMGCR-positive IMNM have been documented in pediatric and young adult populations who have never been exposed to statin medications (4). Case presentation: A 27-year-old man with a history of childhood seizures, but no current medication usage presented with progressive proximal muscle weakness over a two-month period, resulting in falls and requiring wheelchair assistance for mobility. Initial laboratory findings revealed elevated levels of Creatine kinase, aldolase, and transaminases. Muscle biopsy showed scattered regenerating and necrotic muscle fibers with limited chronic lymphoid inflammation consistent with necrotizing myopathy. Positive HMGCR autoantibodies were detected, and other myositis antibody tests were negative. He had never used statin medication. Initial treatment includes corticosteroids, IVIG infusions, and physical therapy. The patient is being followed closely. Discussion: Patients with anti-HMGCR myopathy primarily exhibit skeletal muscle involvement, often without affecting other organs. Consequently, myositis may sometimes be misdiagnosed as muscular dystrophy, particularly in younger individuals. A comprehensive evaluation by healthcare providers is crucial for distinguishing between these conditions. Notably, some cases of anti-HMGCR-positive IMNM may involve diet as a source of statin exposure, as statins are present in red yeast rice and specific mushroom species like Pleurotus spp. and Agaricus bisporus (3,5). Managing anti-HMGCR-positive IMNM poses challenges due to its rarity and the limited availability of clinical trials. Treatment options include corticosteroids, methotrexate, rituximab, and/or IVIG (6). Alternative therapies such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, or cyclophosphamide may also be considered. Additionally, physical therapy plays a crucial role in optimizing function and improving quality of life (7). A longitudinal study has indicated that younger patients often experience more severe disease and a poorer prognosis compared to older patients (8). References: 1. Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, Mammen AL, Miller FW. Idiopathic inflammatory myopathies. Nat Rev Dis Primers. 2021 Dec 2;7(1):86. doi: 10.1038/s41572-021-00321-x. PMID: 34857798. 2. Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011 Mar;63(3):713-21. doi: 10.1002/art.30156. PMID: 21360500; PMCID: PMC3335400. 3. Szczesny, Piotr, et al. "Screening for anti-HMGCR antibodies in a large single myositis center reveals infrequent exposure to statins and diversiform presentation of the disease." Frontiers in Immunology 13 (2022): 866701. 4. Kishi T, Rider LG, Pak K, et al. Association of anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibodies with DRB1*07:01 and severe myositis in juvenile myositis patients. Arthritis Care Res (Hoboken) 2017;69:1088–1094. 5. Barbacki, Ariane, et al. "Immune-Mediated Necrotizing Myopathy and dietary sources of statins." Annals of Internal Medicine 168.12 (2018): 893-904. 6. Meyer, A., Troyanov, Y., Drouin, J. et al. Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients. Arthritis Res Ther 22, 5 (2020). https://doi.org/10.1186/s13075-019-2093-6 7. Alexanderson H. Exercise in Myositis. Curr Treatm Opt Rheumatol. 2018;4(4):289-298. doi: 10.1007/s40674-018-0113-3. Epub 2018 Nov 23. PMID: 30613464; PMCID: PMC6299050. 8. Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, Parks CA, Casciola-Rosen L, Christopher-Stine L, Mammen AL. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017 May 1;56(5):787-794. doi: 10.1093/rheumatology/kew470. PMID: 28096458; PMCID: PMC5850825.

AB - Muscle Mayhem: A Young Adult with Anti-HMGCR Immune-mediated necrotizing Myositis Introduction: Immune-mediated necrotizing myositis (IMNM) is a subset of idiopathic inflammatory myopathies (IIMs), characterized by chronic muscle inflammation and involvement of other organ systems, displaying diverse clinical presentations. While the exact cause remains unknown, these conditions have been linked to factors such as malignancy, exposure to medications, or toxins. Within the IMNM category, a particular subtype is associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myositis-specific autoantibodies (1). In about 67% of cases, this antibody is correlated with prior statin usage (2); although studies suggest a lesser association with statins in certain cases (3). Instances of anti-HMGCR-positive IMNM have been documented in pediatric and young adult populations who have never been exposed to statin medications (4). Case presentation: A 27-year-old man with a history of childhood seizures, but no current medication usage presented with progressive proximal muscle weakness over a two-month period, resulting in falls and requiring wheelchair assistance for mobility. Initial laboratory findings revealed elevated levels of Creatine kinase, aldolase, and transaminases. Muscle biopsy showed scattered regenerating and necrotic muscle fibers with limited chronic lymphoid inflammation consistent with necrotizing myopathy. Positive HMGCR autoantibodies were detected, and other myositis antibody tests were negative. He had never used statin medication. Initial treatment includes corticosteroids, IVIG infusions, and physical therapy. The patient is being followed closely. Discussion: Patients with anti-HMGCR myopathy primarily exhibit skeletal muscle involvement, often without affecting other organs. Consequently, myositis may sometimes be misdiagnosed as muscular dystrophy, particularly in younger individuals. A comprehensive evaluation by healthcare providers is crucial for distinguishing between these conditions. Notably, some cases of anti-HMGCR-positive IMNM may involve diet as a source of statin exposure, as statins are present in red yeast rice and specific mushroom species like Pleurotus spp. and Agaricus bisporus (3,5). Managing anti-HMGCR-positive IMNM poses challenges due to its rarity and the limited availability of clinical trials. Treatment options include corticosteroids, methotrexate, rituximab, and/or IVIG (6). Alternative therapies such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, or cyclophosphamide may also be considered. Additionally, physical therapy plays a crucial role in optimizing function and improving quality of life (7). A longitudinal study has indicated that younger patients often experience more severe disease and a poorer prognosis compared to older patients (8). References: 1. Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, Mammen AL, Miller FW. Idiopathic inflammatory myopathies. Nat Rev Dis Primers. 2021 Dec 2;7(1):86. doi: 10.1038/s41572-021-00321-x. PMID: 34857798. 2. Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011 Mar;63(3):713-21. doi: 10.1002/art.30156. PMID: 21360500; PMCID: PMC3335400. 3. Szczesny, Piotr, et al. "Screening for anti-HMGCR antibodies in a large single myositis center reveals infrequent exposure to statins and diversiform presentation of the disease." Frontiers in Immunology 13 (2022): 866701. 4. Kishi T, Rider LG, Pak K, et al. Association of anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibodies with DRB1*07:01 and severe myositis in juvenile myositis patients. Arthritis Care Res (Hoboken) 2017;69:1088–1094. 5. Barbacki, Ariane, et al. "Immune-Mediated Necrotizing Myopathy and dietary sources of statins." Annals of Internal Medicine 168.12 (2018): 893-904. 6. Meyer, A., Troyanov, Y., Drouin, J. et al. Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients. Arthritis Res Ther 22, 5 (2020). https://doi.org/10.1186/s13075-019-2093-6 7. Alexanderson H. Exercise in Myositis. Curr Treatm Opt Rheumatol. 2018;4(4):289-298. doi: 10.1007/s40674-018-0113-3. Epub 2018 Nov 23. PMID: 30613464; PMCID: PMC6299050. 8. Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, Parks CA, Casciola-Rosen L, Christopher-Stine L, Mammen AL. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017 May 1;56(5):787-794. doi: 10.1093/rheumatology/kew470. PMID: 28096458; PMCID: PMC5850825.

M3 - Conference contribution

BT - Congress of Clinical Rheumatology

ER -