Diagnostic and Therapeutic Challenges in Statin‐Induced Necrotizing Autoimmune Myopathy in an Elderly Patient: A Rare Case Report

ABSTRACT

We present the case of a 78‐year‐old woman with metabolic syndrome and a history of multiple ischemic strokes who developed progressive symmetrical proximal muscle weakness, predominantly affecting the lower extremities, while on atorvastatin. Laboratory evaluation revealed markedly elevated creatine kinase (CK) and positive anti‐HMG‐CoA reductase (anti‐HMGCR) antibodies, with MRI confirming myositis consistent with statin‐induced necrotizing autoimmune myopathy (SINAM). Despite statin discontinuation and immunosuppressive treatment, her muscle weakness persisted, and she remained bedbound at long‐term follow‐up. This case underscores the diagnostic and therapeutic challenges of SINAM in elderly patients with significant comorbidities and highlights the importance of early recognition and tailored management.

Key Clinical Message

Statin‐induced necrotizing autoimmune myopathy should be suspected in patients with progressive symmetrical proximal muscle weakness and persistent creatine kinase elevation despite statin discontinuation. In elderly patients with neurologic comorbidities, diagnosis may be delayed, and anti‐HMGCR antibodies with muscle MRI can be critical when biopsy is not feasible.

1. Introduction

Statins are widely prescribed lipid‐lowering agents with proven benefits in reducing cardiovascular morbidity and mortality. The number of high‐intensity statin users in the United States reached approximately 10.9 million by Q1 2022 [1]. While generally well tolerated, mild self‐limited muscle‐related side effects such as myalgia are relatively common, occurring in approximately 6%–10% of users [2]. However, in rare cases, estimated at 2–3 per 100,000 individuals, patients may develop a serious autoimmune condition known as statin‐induced necrotizing autoimmune myopathy (SINAM) [3].

SINAM is characterized by progressive symmetrical proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and the presence of anti‐HMG‐CoA reductase (anti‐HMGCR) antibodies. Importantly, muscle weakness and enzyme elevation often persist even after discontinuation of statin therapy. The pathogenesis is thought to involve statin‐triggered upregulation of HMG‐CoA reductase in regenerating muscle fibers, leading to the formation of anti‐HMGCR autoantibodies and sustained immune‐mediated myofiber necrosis.

Although the incidence attributable to individual statin agents remains uncertain, published case‐based analyses have identified atorvastatin and simvastatin as the most frequently reported agents, with atorvastatin accounting for the majority of cases. This likely reflects prescribing patterns rather than true differences in immunogenicity [2, 3, 4]. SINAM belongs to the spectrum of immune‐mediated necrotizing myopathies and should be distinguished from anti‐signal recognition particle (anti‐SRP) myopathy, which typically presents with more severe weakness, less association with statin exposure, and a more refractory treatment course [5]. Although skeletal muscle involvement predominates, extra‐muscular manifestations such as interstitial lung disease and myocarditis have also been reported and may contribute to morbidity [6, 7].

In contrast to self‐limited toxic statin‐associated myopathy, which typically resolves within days to weeks after discontinuation of therapy, SINAM represents a persistent immune‐mediated process that does not reliably improve with drug withdrawal alone. Clinical recovery is often prolonged and may require extended immunosuppressive therapy, with some patients experiencing incomplete functional recovery or a relapsing course [8]. In elderly patients, comorbidities and age‐related immune dysregulation may further contribute to delayed recovery and chronic disease behavior.

Diagnosis can be challenging, particularly in elderly patients with multiple comorbidities or pre‐existing neuromuscular deficits, where symptoms may be misattributed to conditions such as stroke or age‐related sarcopenia.

Management of SINAM often requires immunosuppressive agents including corticosteroids, methotrexate, mycophenolate mofetil, or intravenous immunoglobulin (IVIG) [3]. In refractory cases, biologic therapies such as rituximab have shown potential benefit in refractory cases [7]. However, treatment decisions must be carefully individualized, especially in patients with complex medical histories that limit therapeutic options or increase the risk of adverse effects.

Here, we report a diagnostically and therapeutically complex case of SINAM in a 78‐year‐old woman with a history of multiple strokes and poorly controlled diabetes, underscoring the challenges in recognition, treatment, and functional recovery in high‐risk populations.

2. Case History/Examination

We present the case of a 78‐year‐old woman with a history of hypercholesterolemia, multiple ischemic strokes, and type 2 diabetes mellitus, who was evaluated in December 2017 for progressive symmetrical proximal muscle weakness. A chronological summary of key clinical events and interventions is provided in Table 1 (see Timeline Table).

TABLE 1.

Chronological summary of key events in a patient with statin‐induced necrotizing autoimmune myopathy.

2003	Ischemic stroke with residual right lower extremity weakness
2013	Initiation of atorvastatin therapy for hypercholesterolemia
2017 (4 years post‐statin)	Symptom onset: progressive proximal muscle weakness (bilateral lower extremities > upper extremities)
July 2017	Deep vein thrombosis (DVT) with pulmonary embolism (PE); anticoagulation started
4 months pre‐presentation	Hospital admission for altered mental status; CK > 2000 IU/L; atorvastatin discontinued
Presentation and diagnosis (December 2017)	Persistent CK elevation (5909 IU/L), positive anti‐HMGCR antibodies, MRI‐confirmed myositis; SINAM diagnosis established
Treatment initiated (December 2017)	Methotrexate (25 mg SC weekly) + prednisone (20 mg daily) + folic acid
During treatment	Worsening glycemic control (HbA1c > 11%); methotrexate discontinued; mycophenolate mofetil (500 mg daily) initiated
8‐year follow‐up (2025)	CK near‐normal levels; persistent bedbound status due to unresolved weakness; managed by primary care physician with mycophenolate

Her long‐term medication regimen included aspirin, clopidogrel, docusate sodium, furosemide, glipizide, insulin glargine, lisinopril, metoprolol tartrate, rivaroxaban, dapagliflozin, ergocalciferol, and folic acid. She denied use of medications associated with potentiation of statin‐related myotoxicity, including allopurinol, colchicine, and hydroxychloroquine [9]. She had been on atorvastatin since 2013.

On physical examination, she was alert and oriented, with stable vital signs (blood pressure 139/74 mmHg, pulse 60 bpm, oxygen saturation 96%). General examination was unremarkable, with no signs of cyanosis, edema, or joint abnormalities. Neurological examination revealed normal mental status, cranial nerve function, motor tone, and coordination, with preserved sensation in all extremities. Muscle strength testing demonstrated significant symmetrical proximal weakness in the hip flexors, abductor muscles, and knee extensors (1/5 bilaterally), with preserved upper extremity strength (5/5). There were no cutaneous features of myositis, such as heliotrope rash or Gottron's papules. Baseline neurological deficits from a prior ischemic stroke (2003) included mild right lower extremity weakness.

3. Differential Diagnosis, Investigations, and Treatment

Laboratory investigations revealed normal hematological, inflammatory, renal, hepatic, thyroid, and coagulation profiles. Creatine kinase (CK) was markedly elevated at 5909 IU/L and anti‐HMGCR antibodies were positive. Antinuclear antibody (ANA) and rheumatoid factor (RF) were negative.

Cardiac evaluation, including electrocardiography and echocardiography, showed no evidence of myocarditis. CK‐MB and troponin levels were not suggestive of myocardial injury. Chest imaging did not demonstrate interstitial lung disease. Magnetic resonance imaging (MRI) of the lower extremities demonstrated global, symmetric, active, and chronic myositis involving the pelvic and thigh musculature, with no significant fasciitis (Figures 1 and 2). Electromyography (EMG) was inconclusive for myopathy, limited by anticoagulation and lower extremity swelling.

FIGURE 1.

Axial T1‐weighted MRI images of the lower legs at comparable anatomical levels. The images demonstrate diffuse, marked muscle atrophy with prominent fatty replacement involving multiple muscle compartments, more severe on the left (A) than the right (B).

FIGURE 2.

Axial STIR MRI images of the lower legs at comparable anatomical levels. Hyperintense signal changes (white arrows) in multiple muscle compartments indicate diffuse intramuscular edema, consistent with active inflammation associated with necrotizing autoimmune myopathy. Left (A), Right (B).

At presentation, atorvastatin had already been discontinued following a prior hospitalization 4 months earlier for altered mental status and elevated CK (> 2000 IU/L).

Given her comorbidities, including prior cerebrovascular disease, intravenous immunoglobulin (IVIG) was not pursued due to concerns regarding thrombotic risk. Initial treatment consisted of methotrexate (25 mg subcutaneously weekly) and prednisone (20 mg daily), along with folic acid supplementation. Pulse intravenous methylprednisolone was not administered due to the absence of life‐threatening organ involvement and concerns regarding metabolic decompensation in the setting of poorly controlled diabetes and advanced age.

There was no significant clinical improvement, and glycemic control deteriorated, with HbA1c rising from 6% to > 11%. Prednisone and methotrexate were discontinued after limited response, and mycophenolate mofetil (500 mg daily) was introduced. This resulted in a favorable biochemical response, with CK levels gradually returning to near‐normal levels (Figure 3).

FIGURE 3.

Creatine kinase (CK) levels over time in a patient with statin‐induced necrotizing autoimmune myopathy.

4. Conclusion and Results (Outcome and Follow‐Up)

Despite biochemical improvement, the patient did not regain ambulatory function and remained bedbound with persistent weakness of both upper and lower extremities. She was subsequently lost to specialty follow‐up due to functional immobility and limited access to tertiary care and was managed by her primary care physician, who continued mycophenolate therapy. Follow‐up MRI was not performed due to clinical and logistical limitations.

On long‐term follow‐up (2025), CK levels remained near normal; however, the patient remained bedbound, raising concern for irreversible muscle damage and/or residual neurological impairment from prior cerebrovascular disease. In the absence of follow‐up imaging or biopsy, differentiation between persistent autoimmune activity and fixed functional deficit was not possible. The prolonged disease course also had a significant psychosocial impact, although formal psychological assessment was not performed.

5. Discussion

SINAM is a rare, immune‐mediated condition characterized by persistent muscle injury after statin exposure, mediated by the production of anti‐HMGCR antibodies. Unlike typical statin myopathy, which is dose‐dependent and reversible upon discontinuation, SINAM may progress despite statin cessation and requires immunosuppression for disease control [2, 3, 4].

There are no universally accepted diagnostic criteria for SINAM. However, clinical algorithms based on expert consensus recommend initial evaluation with creatine kinase (CK) testing in any patient on statins who presents with muscle symptoms (Figure 4). A CK level exceeding 10 times the upper limit of normal (ULN) should raise suspicion for immune‐mediated necrotizing myopathy, warranting immediate discontinuation of the statin. Levels above 15 times the ULN, particularly if accompanied by myoglobinuria or renal dysfunction, suggest possible rhabdomyolysis and require urgent management [10, 11, 12].

FIGURE 4.

Diagnostic algorithm for statin‐associated myopathy. CK, Ccreatine kinase (values are approximate); EMG, Eelectromyography; HMGCR, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase; IMNM, Iimmune‐mediated necrotizing myopathy. The dotted line indicates that muscle biopsy is not always mandatory.

Further diagnostic evaluation includes serologic testing for myositis‐specific antibodies, particularly anti‐HMGCR antibodies, which are highly sensitive and specific for SINAM. While muscle biopsy remains a useful tool, it is not mandatory when other diagnostic modalities—such as antibody positivity and imaging—are supportive [13]. In this case, muscle biopsy was deferred due to the patient's frailty, anticoagulation risks, and the diagnostic confidence provided by MRI and serologic findings. Electromyography (EMG) and MRI are also helpful adjuncts: EMG typically reveals irritable myopathic changes, and MRI often shows diffuse, symmetrical muscle edema on STIR sequences, as seen in our patient [3].

5.1. Management Considerations

Treatment of SINAM typically involves discontinuation of the statin and initiation of immunosuppressive therapy. First‐line agents include corticosteroids, often combined with steroid‐sparing agents such as methotrexate, mycophenolate mofetil, or azathioprine. In cases of severe or refractory disease, IVIG or rituximab may be considered [13, 14]. Rituximab has been used as a second‐ or third‐line agent in refractory immune‐mediated necrotizing myopathies, particularly in patients with anti‐HMGCR and anti‐SRP antibodies. Although evidence is limited to retrospective cohorts and expert consensus reports, including the expert international neuromuscular panel (ENMC) workshop experience, some patients achieve partial or complete remission, while others show variable or incomplete response, highlighting heterogeneity in treatment outcomes and the need for individualized therapy [15].

In our patient, multiple barriers impacted treatment. The patient was unable to tolerate high‐dose corticosteroids and methotrexate, and although IVIG might have offered clinical benefit, it was avoided due to concerns about thrombotic risk in the setting of atrial fibrillation, diabetes, and prior cerebrovascular disease. Agents like rituximab could also have been considered, but her frailty and comorbid conditions limited aggressive immunosuppressive strategies. Ultimately, mycophenolate mofetil was selected as the safest long‐term option.

5.2. Comparison to Literature

Previous case reports have highlighted favorable outcomes in SINAM with early initiation of immunosuppressive therapy. Joudeh et al. described a patient who regained independent ambulation and was discharged on a tapering course of oral steroids, while De Cock et al. reported near‐complete recovery of muscle strength within 1 year [14, 16]. In contrast, our patient demonstrated biochemical improvement without corresponding functional recovery, likely due to delayed diagnosis, the inability to initiate first‐line therapies such as IVIG, and significant pre‐existing neurological deficits.

5.3. Prognosis and Long‐Term Outcomes

Prognosis in SINAM is variable and is influenced by the timing of diagnosis, prompt initiation of immunosuppressive therapy, and the presence of comorbidities [17]. Older adults with significant pre‐existing neurological deficits or delayed diagnosis, as in our patient, are less likely to achieve meaningful functional recovery despite biochemical remission. In our case, despite normalization of CK levels, the patient remained bedbound, highlighting the potential for irreversible deficits in this population. Chronic immune‐mediated myopathies may also be associated with significant psychosocial burden and may coexist with fibromyalgia, both of which can adversely affect quality of life and complicate clinical assessment. Prior studies in idiopathic inflammatory myopathies have shown that comorbid fibromyalgia is associated with greater disability, worse fatigue, and higher rates of depression and anxiety [18]. Although formal psychological assessment was not performed in our patient, prolonged functional dependence and persistent weakness likely contributed to substantial psychosocial distress.

5.4. Broader Implications

As statins are widely prescribed for cardiovascular risk reduction, especially in older adults with multiple comorbidities, this case underscores the importance of vigilant monitoring for rare but serious complications such as SINAM. Clinicians should consider individualized risk–benefit assessments before initiating statin therapy in high‐risk populations. Additionally, interactions with medications that inhibit CYP3A4 may increase serum statin levels and predispose to immune‐mediated muscle injury.

6. Conclusions and Limitations

Although the patient's CK levels normalized, her functional status did not improve, suggesting the possibility of irreversible muscle damage or ongoing neurological impairment. A key limitation of this case was the absence of formal functional assessments (e.g., MRC scale, Barthel Index), which could have provided objective tracking of muscle strength and daily function over time. Incorporating such tools in future cases could improve clinical decision‐making and outcome comparisons. Furthermore, patient and caregiver education on the chronic nature of SINAM and the importance of immunosuppressive therapy adherence and regular follow‐up is critical for preventing relapse. This case report is also limited by the lack of a muscle biopsy, the patients loss to follow up, and the inability to definitively differentiate between SINAM‐related muscle weakness and deficits from prior cerebrovascular disease, due to the absence of pretreatment functional measurements. Further research is needed to establish evidence‐based management guidelines and identify predictors of functional recovery in elderly patients with multiple comorbidities.

Author Contributions

Nischal Shrestha: conceptualization, data curation, investigation, methodology, supervision, validation, writing – original draft, writing – review and editing. Abdirahman Hassan: conceptualization, supervision, writing – review and editing. Jennifer Ann Evans: writing – review and editing.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

All data supporting the findings of this case report are included within the article. Further data will be provided upon request.