Management of Challenging Cases in Myositis

Dr. Aggarwal also touched on treatment, emphasizing the efficacy of rituximab, particularly for the first case, and its demonstrated benefit in increases in FVC and DLCO for refractory ILD. He also highlighted the advent of CAR T cell therapy as a paradigm shift in the management of myositis, noting its ability to effect sustained improvements in CK, anti-Jo-1 antibody levels, manual muscle testing, patient global activity scores and even ILD fibrosis.²

Immune-Mediated Necrotizing Myopathy

Dr. Eleni Tiniakou

The talk shifted focus to the presentation and management of a similar yet distinct form of inflammatory myopathy—immune mediated necrotizing myopathy (IMNM), presented by Eleni Tiniakou, MD, associate professor of medicine and director of the myositis clinic in the Division of Rheumatology at University of Texas Health Science Houston, McGovern Medical School.

IMNM is a new term, first defined in 2004, which refined our understanding of the now-outdated term polymyositis. Clinically, IMNM is characterized by proximal muscle weakness, with marked elevations in CK levels, typically over at least 1,000. Biopsies demonstrate necrosis, myophagocytosis, and a macrophage predominance. IMNM can either be seronegative or seropositive with anti-HMGCR or SRP autoantibodies, which help further characterize the disease phenotype.

Dr. Tiniakou shared a cautionary tale of a 65-year-old man with prior statin exposure who presented with diffuse weakness and a CK of 42,000. Did this represent IMNM or statin (toxic) myopathy? She emphasized that neither EMG, MRI nor muscle biopsy would be able to differentiate between the two entities and that the physician must rely on the patient’s clinical trajectory. The patient’s CK resolved to <1,000 by day 10 in the absence of treatment, supporting the diagnosis of statin myopathy, rather than IMNM.

In the second case, Dr. Tiniakou recalled a patient diagnosed with seronegative IMNM who was unusually refractory to steroids, methotrexate and mycophenolate, leading her to question the diagnosis. Thyroid studies demonstrated undetectable free T4, and the patient was diagnosed with myopathy secondary to central hypothyroidism and empty sella syndrome. With thyroid replacement, the patient’s weakness slowly improved. This case underscored the importance of considering alternative diagnoses, particularly endocrinopathies, in patients with continued weakness despite immunosuppressive treatment.

In another case, she emphasized that younger patients with anti-SRP IMNM tend to have more aggressive disease. She advocated for the use of rituximab and steroids up front in cases of moderate to severe IMNM due to anti-SRP, and IVIG and steroids in anti-HMGCR positive IMNM, which is reflected in consensus recommendations for IMNM.^3-5 She reviewed the limited evidence for plasmapheresis and cyclophosphamide, which may be options in cases of aggressive disease.