Case presentation

A 51-year-old man with a history of type 2 diabetes mellitus (HbA1c 9.6%), hyperlipidemia on long-term rosuvastatin and ezetimibe, hypertension, coronary artery disease status post coronary artery bypass grafting (CABG) and multiple stents, and heart failure with recovered ejection fraction of 50% presented with one week of progressive diffuse back pain, bilateral proximal weakness, and dark urine. He denied trauma, exertion, immobilization, seizures, drug use, alcohol, or recent viral illness. Medication regimen at presentation: metformin 500 mg BID, rosuvastatin 40 mg, Zetia 10 mg, Entresto 24-26 mg, aspirin 81 mg, ticagrelor 90 mg, and metoprolol 50 mg.

On arrival, he was hemodynamically stable and afebrile. Neurological exam revealed 4/5 hip flexion strength bilaterally with preserved distal strength. The remainder of the exam was otherwise unremarkable.

Initial laboratory testing

Significant values include CK 24,700 U/L, creatinine 2.37 mg/dL (baseline ~1), BUN 31 mg/dL, AST 584 U/L, ALT 638 U/L, and glucose 347 mg/dL (Table 1). Urinalysis showed heme positivity with absent RBCs and granular casts.

Test name | Result | Normal range
Creatine kinase (CK) | 24,700 U/L | 30-200 U/L (males)
30-135 U/L (females)
Creatinine | 2.37 mg/dL | 0.3-1.2 mg/dL
(baseline ~1 mg/dL)
Blood urea nitrogen (BUN) | 31 mg/dL | 9.5-46.3 mg/dL
Aspartate aminotransferase (AST) | 584 U/L | 12-60 U/L
Alanine aminotransferase (ALT) | 638 U/L | 11.2-48.0 U/L (males)
4.3-37 U/L (females)
Glucose | 347 mg/dL | 65-125 mg/dL
Urinalysis - heme | Positive | Negative
Urinalysis - red blood cells | Absent | 0-2 per high-power field
Urinalysis - casts | Granular casts present | None or occasional hyaline casts
Thyroid-stimulating hormone (TSH) | Normal | 0.4-4.0 mIU/L (approximate)
Antinuclear antibody (ANA) | Negative | Negative
Anti-HMG-CoA reductase antibody | Negative | Negative
Anti-histidyl-tRNA synthetase (anti-Jo-1) | Negative | Negative
Toxicology screen | Negative | Negative

Imaging

MRI of the thighs demonstrated diffuse STIR hyperintensity with contrast enhancement involving multiple proximal muscle groups, consistent with myositis (Figure 1). Lumbar spine MRI showed degenerative disc changes without evidence of radiculopathy.

Figure 1: MRI lower-extremity non-joint with/without IV contrastMRI lower-extremity non-joint with/without IV contrast showing diffuse high short TI inversion recovery (STIR) signal with associated enhancement involving bilateral thigh musculature, most prominent in the mid to distal portion of the right sartorius muscle, right mid semimembranosus muscle, and left rectus femoris.

The patient was managed with aggressive IV fluids, strict input/output monitoring, and discontinuation of statins. Renal function stabilized, and CK initially trended downward on hospital day two. However, the patient’s CK continued to uptrend on day three of his hospitalization, progressing from an initial 24,700 to 26,200 despite fluids (Table 2). The continued elevation of CK suggested an autoimmune inflammatory etiology of the rhabdomyolysis and prompted further investigation. Eventually, after one week of hospitalization, he improved clinically and was discharged with outpatient neurology and rheumatology follow-up for EMG and muscle biopsy.

Date | HD1 08:00 | HD2 16:00 | HD2 22:00 | HD3 11:00 | HD4 08:00 | HD4 12:00 | HD4 16:00 | HD5 12:00 | HD6 08:00 | HD7 09:00 | HD8 06:00
CK (U/L) | 24700 | 18100 | 26200 | 18693 | 16983 | 17906 | 13713 | 9634 | 5885 | 3618 | 1875

The patient’s CK and creatinine eventually improved with supportive management. He was discharged in stable condition with outpatient follow-up for EMG and muscle biopsy to confirm suspected seronegative immune-mediated necrotizing myopathy.

On the outpatient follow-up, the patient’s CK normalized and inflammatory markers were negative. Definitive diagnosis of immune-mediated necrotizing myopathy is dependent on muscle biopsy, which is still pending for the patient to undergo. However, the dramatic improvement with statin cessation and supportive care, initial clinical presentation, and MRI findings remain highly suspicious for immune-mediated necrotizing myopathy.