{"id":11084,"date":"2026-06-08T12:33:22","date_gmt":"2026-06-08T12:33:22","guid":{"rendered":"https:\/\/www.kauveryhospital.com\/ima-journal\/?p=11084"},"modified":"2026-06-11T12:12:47","modified_gmt":"2026-06-11T12:12:47","slug":"severe-hyperckemia-and-myoglobinuria-in-statin-exposure-a-case-of-seronegative-necrotizing-autoimmune-myopathy","status":"publish","type":"post","link":"https:\/\/www.kauveryhospital.com\/ima-journal\/ima-journal-june-2026\/severe-hyperckemia-and-myoglobinuria-in-statin-exposure-a-case-of-seronegative-necrotizing-autoimmune-myopathy\/","title":{"rendered":"Severe HyperCKemia and Myoglobinuria in Statin Exposure: A Case of Seronegative Necrotizing Autoimmune Myopathy"},"content":{"rendered":"

[vc_section][vc_row][vc_column][vc_column_text]<\/p>\n

Abstract<\/h2>\n

Immune-Mediated Necrotizing Myopathy (IMNM) is a rare and severe subtype of idiopathic inflammatory myopathy characterized by rapidly progressive proximal muscle weakness, markedly elevated serum creatine phosphokinase (CPK) levels, and muscle fibre necrosis with minimal inflammatory infiltrates. Statin exposure is a well-recognized trigger, although seronegative cases are increasingly reported.<\/p>\n

Keywords<\/h2>\n

Immune-mediated necrotizing myopathy, Statin-induced myopathy, HyperCKemia, Myoglobinuria, Inflammatory myopathy, Anti-HMGCR-negative myopathy<\/p>\n

Introduction<\/h2>\n

Immune-Mediated Necrotizing Myopathy (IMNM) is identified to have various etiologies. Among the various etiologies, statin-induced immune-mediated necrotizing myopathy has gained increasing recognition due to the widespread use of statins in cardiovascular disease prevention.<\/p>\n

Unlike self-limiting toxic statin myopathy, IMNM persists even after discontinuation of statins because of an autoimmune process directed against muscle fibres. Patients often present with profound muscle weakness, myoglobinuria, dysphagia, and significantly elevated muscle enzymes. Early diagnosis and aggressive immunosuppressive therapy are essential to prevent morbidity and improve functional outcomes.<\/p>\n

We report a case of acute inflammatory necrotizing myopathy, probably statin induced, in an elderly female who presented with severe proximal muscle weakness and markedly elevated CPK levels, with subsequent improvement following pulse methylprednisolone therapy.<\/p>\n

Case Presentation<\/h2>\n

A 69-year-old female with a known history of rheumatoid arthritis, systemic hypertension, seizure disorder, coronary artery disease status post single vessel PTCA and chronic statin use presented with progressive proximal muscle weakness involving both upper and lower limbs. The weakness was severe enough to impair ambulation and daily activities.<\/p>\n

Initial evaluation revealed gross elevation of serum creatine phosphokinase (CPK) associated with myoglobinuria, suggestive of severe muscle injury. Clinical findings were consistent with an inflammatory myopathy. There was no evidence of active malignancy on evaluation with PET-CT, which demonstrated only low-grade muscle inflammation without evidence of neoplastic disease.<\/p>\n

Myositis profile revealed weak positivity for PM-Scl antibodies, which was considered clinically insignificant. Anti-HMG-CoA reductase antibody testing was negative.<\/p>\n

During the course of illness, the patient developed recent left lower limb proximal deep vein thrombosis with pulmonary embolism. ANA profile and antiphospholipid antibody screening were negative.<\/p>\n

Management and Outcome<\/h2>\n

On examination during follow-up, the patient showed significant clinical improvement following treatment with pulse intravenous methylprednisolone. She became ambulatory with improvement in muscle symptoms. Residual proximal muscle power in bilateral upper and lower limbs was graded 3\/5 initially, later progressing to normal muscle power on subsequent follow-up.<\/p>\n

There was no active inflammatory joint pain at follow-up. A subtle facial rash was noted, though its clinical significance remained uncertain.<\/p>\n

Based on the clinical presentation, markedly elevated CPK, proximal muscle weakness, myoglobinuria, exclusion of malignancy, and favorable response to corticosteroid therapy, a diagnosis of acute inflammatory necrotizing myopathy, probably statin induced, was made.<\/p>\n

Discussion<\/h2>\n

The differential diagnoses considered included toxic statin myopathy, polymyositis, dermatomyositis, rheumatoid arthritis-associated myositis, inclusion body myositis, viral myositis, and paraneoplastic necrotizing myopathy. The combination of severe proximal weakness, markedly elevated CPK, myoglobinuria, exclusion of malignancy, and favorable response to immunosuppressive therapy supported the diagnosis of probable statin-associated IMNM despite negative anti-HMGCR antibodies.<\/p>\n\n\n\n\n\n\n
Differential Diagnosis<\/strong><\/td>\nFeatures Supporting Diagnosis in This Case<\/strong><\/td>\nFeatures Against Diagnosis in This Case<\/strong><\/td>\nWhy IMNM was favoured<\/strong><\/td>\n<\/tr>\n
Statin-induced toxic myopathy (non-immune)<\/td>\nHistory suggestive of statin exposure after PTCA, proximal weakness, elevated CPK<\/td>\nVery severe CPK elevation, myoglobinuria, persistent symptoms, required pulse steroids, ongoing inflammatory pattern<\/td>\nToxic myopathy usually improves after stopping statin alone; persistent severe necrosis favors IMNM<\/td>\n<\/tr>\n
Polymyositis<\/td>\nSymmetrical proximal weakness, elevated inflammatory markers, steroid responsiveness<\/td>\nMinimal inflammatory findings on PET-CT, severe necrotic pattern, gross CPK elevation, myoglobinuria more typical of IMNM<\/td>\nNecrosis predominated over inflammation, consistent with IMNM<\/td>\n<\/tr>\n
Dermatomyositis<\/td>\nSubtle facial rash, proximal weakness, elevated muscle enzymes<\/td>\nNo heliotrope rash, Gottron papules, shawl sign, or malignancy; rash minimal and nonspecific<\/td>\n\n\n\n\n\n\n\n\n\n
Lack of classical cutaneous findings and predominant necrotizing picture supported IMNM<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/td>\n<\/tr>\n
Inclusion Body Myositis<\/td>\nElderly age group, muscle weakness<\/td>\nAcute presentation, proximal > distal weakness, gross CPK elevation, steroid responsiveness, myoglobinuria uncommon in IBM<\/td>\nIBM is slowly progressive with mild CPK rise and poor steroid response<\/td>\n<\/tr>\n
Rheumatoid arthritis-associated myositis \/ overlap syndrome<\/td>\nKnown rheumatoid arthritis, weak PM-Scl positivity<\/td>\nPM-Scl weak and clinically insignificant, no ILD\/systemic sclerosis overlap, severe necrotizing pattern is atypical<\/td>\nMuscle injury severity and necrosis favored IMNM<\/td>\n<\/tr>\n
Paraneoplastic necrotizing myopathy<\/td>\nElderly patient, severe myopathy raises suspicion for occult malignancy<\/td>\nPET-CT negative for malignancy, no constitutional symptoms, good steroid response<\/td>\nMalignancy workup was negative, making paraneoplastic etiology less likely<\/td>\n<\/tr>\n
Viral Myositis<\/td>\nAcute onset weakness, elevated CPK, myoglobinuria<\/td>\nNo febrile illness or infectious prodrome, persistent course, autoimmune steroid-responsive pattern<\/td>\nClinical course was more consistent with autoimmune necrotizing myopathy<\/td>\n<\/tr>\n
Drug-induced myopathy (other than statins)<\/td>\nElderly patient with possible polypharmacy, elevated muscle enzymes<\/td>\nNo alternative offending drug identified, severity disproportionate to routine toxic myopathy<\/td>\nStatin-associated immune-mediated process better explained the presentation<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

This overall clinicobiochemical profile strongly supports immune-mediated necrotizing myopathy, probably statin induced.<\/p>\n

Management includes immediate cessation of statins and initiation of aggressive immunosuppressive therapy. High-dose corticosteroids remain first-line treatment, often combined with steroid-sparing agents or IVIG in refractory disease. Early treatment is associated with better functional recovery.<\/p>\n

This patient demonstrated substantial clinical recovery following pulse methylprednisolone therapy, highlighting the importance of early recognition and treatment.<\/p>\n

Conclusion<\/h2>\n

Acute inflammatory necrotizing myopathy is a rare but potentially disabling inflammatory muscle disease that should be considered in patients presenting with severe proximal muscle weakness and markedly elevated CPK levels, especially in the setting of statin exposure. Early diagnosis, exclusion of malignancy, and prompt immunosuppressive therapy are crucial for favorable outcomes.<\/p>\n

This case emphasizes that statin-induced necrotizing myopathy may occur even in the absence of anti-HMGCR antibodies and can respond well to corticosteroid therapy.Top of Form<\/p>\n

References<\/h2>\n
    \n
  1. Patel S, Abu-Abaa M, Mousavi F. Seronegative Immune-Mediated Necrotizing Myopathy: A Case Report. Cureus. 2022 Aug 9;14(8):e27824. doi: 10.7759\/cureus.27824. PMID: 36106264; PMCID: PMC9452053.<\/li>\n
  2. Seronegative Immune-Mediated Necrotizing Myopathy Presenting as Acute Onset Quadriparesis. (2025).\u00a0European Journal of Medical and Health Sciences,\u00a07(5), 13-16. https:\/\/doi.org\/10.24018\/ejmed.2025.7.5.2407<\/li>\n
  3. Seronegative statin induced Immune-Mediated Necrotizing Myopathy<\/li>\n<\/ol>\n

    Zeel J. Patel;\u00a0Lekha Racharla;\u00a0Akhil Kher;\u00a0Rahul Gupta;\u00a0Andrew D. SumnerJACC (Journal of the American College of Cardiology), March 08, 2022, Volume 79, Issue 9, Pages 3181-3181<\/p>\n

      \n
    1. Pinal-Fernandez, I., Casal-Dominguez, M. & Mammen, A.L. Immune-Mediated Necrotizing Myopathy.\u00a0Curr Rheumatol Rep\u00a020<\/strong>, 21 (2018).https:\/\/doi.org\/10.1007\/s11926-018-0732-6<\/li>\n<\/ol>\n
      \n
      \"Dr<\/div>\n
      \n

      Dr. Sham S
      \nSenior Consultant Rheumatology,
      \nKauvery Hospital, Chennai.<\/a><\/b><\/p>\n<\/div>\n<\/div>\n

      \n
      \"Dr<\/div>\n
      \n

      Dr. Roseline Sweety Jebapriya N
      \nDNB Resident Internal Medicine,
      \n      Kauvery Hospital, Chennai.<\/a><\/b><\/p>\n<\/div>\n<\/div>\n

      [\/vc_column_text][\/vc_column][\/vc_row][\/vc_section]<\/p>\n","protected":false},"excerpt":{"rendered":"

      [vc_section][vc_row][vc_column][vc_column_text] Abstract Immune-Mediated Necrotizing Myopathy (IMNM) is a rare and severe subtype of idiopathic inflammatory myopathy characterized by rapidly progressive proximal muscle weakness, markedly elevated serum creatine phosphokinase (CPK) levels,<\/p>\n","protected":false},"author":2,"featured_media":11087,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[101],"tags":[],"class_list":["post-11084","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ima-journal-june-2026"],"yoast_head":"\nSevere HyperCKemia and Myoglobinuria in Statin Exposure: A Case of Seronegative Necrotizing Autoimmune Myopathy<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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