A 69-year Caucasian woman presented at age 63 with progressive upper and lower limb weakness over a 6-month period. Physical examination revealed distal and proximal weakness with no features of extra-muscular disease. Initial creatine kinase (CK) was approximately 6000 iU/L, and single fibre necrosis, predominantly macrophagic inflammation with upregulation of major histocompatibility complex (MHC) Class I at the periphery of fibres and regeneration suggestive of necrotising myopathy was identified on the needle muscle biopsy of the quadriceps muscle (Fig. 1). Autoimmune serology including anti-nuclear antibodies, myositis antibody panel [2] and anti-HMGCR antibody were negative. The presence of anti-HMGCR antibody was assayed for using an in-house developed ELISA method using a commercially available antigen (Sigma-Aldrich) that has been validated against a commercial assay [6].
Malignancy screen including mammogram, computed tomography (CT) body, positron-emission tomography scan and colonoscopy did not suggest any evidence of concurrent malignancy.
Her past medical history included hyperlipidaemia. She commenced 20 mg simvastatin at age 59 but development of myalgia prompted a switch to atorvastatin 40 mg with an initial resolution of symptoms. Statins were permanently discontinued at age 62 by her primary care physician due to return of her symptoms of myalgia.
Treatment was commenced 1 year after onset of the symptoms (September 2013) with 40 mg oral prednisolone. This was tapered down over time and stopped 18 months later. Her CK, which had peaked at 10,527 iU/L 15 months from the onset, had fallen to 658 iU/L after 9 months of prednisolone treatment when methotrexate was introduced (Fig. 2).
During a prolonged period of relative stability, the patient required several weaning courses of prednisolone due to minor clinical and biochemical flares but had remained mostly symptom-free with stable CK levels (Fig. 3). 10 mg per day of prednisolone was re-started due to a rising CK with worsening muscle weakness in June 2015, with methotrexate increased to 15 mg per week. Prednisolone was increased to 40 mg in July 2015 after the patient continued to worsen clinically. This was weaned down by 10 mg per calendar month to 10 mg in November 2015, reducing to 5 mg for December 2015 and stopping in January 2016. HMGCR antibody was retested and was negative in June 2016. Methotrexate was increased to 17.5 mg once weekly in January 2017 due to an asymptomatic rise in CK. She was given 10 mg prednisolone for 1 month in June 2017 to treat a clinical deterioration to good effect. While she largely remained in remission clinically, her CK levels remained raised at a low level suggestive of a partial biochemical remission.
Six years from the onset (May 2018), the patient experienced rapidly worsening proximal weakness with deteriorating mobility and a rising CK to approximately 6000. Magnetic resonance imaging (MRI) of muscles confirmed significant oedema (Fig. 3, panel A & B). A repeat autoimmune screen revealed the presence of anti-HMGCR antibody, detected using the same in-house assay which demonstrated negative results on two previous separate occasions. She received two cycles of rituximab (1 g on day 1 and day 15) 6 months apart. A repeat MRI muscles 3 months after second course of rituximab showed resolution of muscular oedema (Fig. 3, panel C & D), with corresponding clinical and biochemical improvement (CK 600 iU/L). Her anti-HMGCR antibody was re-tested using a commercially available assay (QUANTA Flash, Inova Diagnostics) in December 2019 which confirmed a positive result. The patient remains well and has not required further rituximab therapy. She remains under active review.