Case Presentation: A 65-year-old male with past medical history significant for hepatocellular carcinoma on duravalumab and tremelimumab, liver cirrhosis secondary to hepatitis C, portal vein thrombosis on anticoagulation, hypertension presented to the hospital with diffuse muscle pains, proximal muscle weakness, skin rash, urinary and fecal incontinence which started 5 days prior to presentation. The patient received his first cycle (C1D1) of duravalumab and tremelimumab 5 weeks prior to the presentation. His second cycle was postponed due to an elevated transaminase level. He was tachycardic (HR 103 bpm), afebrile and normotensive. Physical exam pertinent for 4/5 power shoulder abduction, tenderness was elicited upon palpation of bilateral shoulders and hips, a violaceous rash on the lateral bilateral thighs, diffuse erythematous rash over the upper chest and bilateral arms with sparing of the hands.Initial laboratory testing revealed elevated transaminases (AST: 1487 IU/L, ALT: 583 IU/L), elevated troponin (hs troponin:1158 ng/L) and creatine kinase (CK) of 388 IU/L. Six hours later, troponin peaked at 1438 ng/L and CK at 16,061 IU/L; aldolase was raised at 192 IU/L. EKG showed no ischemic changes; echocardiography demonstrated preserved ejection fraction with no regional wall motion abnormalities. Cardiac MRI ruled out myocarditis.MRI total spine excluded cord compression. Electromyography (EMG) demonstrated a myopathic process in the proximal upper limb muscles. Autoantibody testing was negative for acetylcholine receptor and anti- muscle – specific tyrosine kinase antibodies. Anti- striation antibodies were elevated (1:320), although an extended myositis panel was otherwise negative. MRI bilateral thighs showed bilateral thigh, gluteal and hamstring muscles atrophy and active inflammation consistent with myositisThe patient was treated with intravenous methylprednisolone (1g daily for 5 days), followed by oral prednisolone (2 mg/kg/day), eventually tapered by 0.5 mg/kg every 2 weeks. Weakness, muscle pain and fecal incontinence resolved by hospital day 4. His liver enzymes improved at the time of discharge. Urinary incontinence resolved three weeks post-discharge. Immunotherapy was discontinued due to grade 4 immune mediated hepatitis. He underwent stereotactic body radiation therapy to liver.
Discussion: Immune checkpoint inhibitor (ICI)-associated myositis occurs in approximately 1% of treated patients and often coexists with myocarditis or myasthenia gravis—overlap syndromes associated with high mortality (1-3) . The diagnostic criteria for ICI-related myositis, as described by Tout et al. and Matas–Garcia et al., require either one major (histopathologic) or three minor criteria—(a) elevated muscle enzymes, (b) EMG showing a myopathic pattern, and (c) MRI/PET suggesting muscle inflammation. Our patient met all three minor criteria, confirming the diagnosis without biopsy. Prompt recognition and high-dose corticosteroid therapy led to rapid improvement.
Conclusions: Durvalumab and tremelimumab can trigger severe immune-mediated myositis. With ICIs becoming central to HCC management, clinicians must maintain a high index of suspicion for atypical presentations. Early recognition, discontinuation of immunotherapy, and prompt corticosteroid initiation are critical to reduce morbidity and prevent fatal complications