History
A male patient in his 70s has a history of obstructive sleep apnea, hypertension and hyperlipidemia treated with atorvastatin for three years.
Five months prior to coming to Rush, the patient experienced difficulty with swallowing and painless weakness in all his extremities. He experienced five falls during the first month of symptoms, which he attributed to the loss of balance and leg weakness.
His limb weakness was bilateral in both the upper and lower extremities and was more pronounced in the upper aspect of the limbs. It had been progressive but the same throughout the day. He had been non-ambulatory for two months and transitioned to residing in a nursing home.
His swallowing function worsened over time, and he had to clear his throat while eating. He was placed on a pureed diet two weeks prior to his evaluation at Rush. He denied nasal regurgitation of liquids or food. The patient unintentionally lost 45 pounds since the onset of weakness.
His family noted a change in his speech as if it were strained.
In the month prior to his visit at Rush, he also experienced shortness of breath and productive cough with white mucus. The patient said he had a fever three weeks prior to his Rush appointment, but was COVID negative, and had no fevers since then or preceding the swallowing difficulty or extremity weakness.
Two months prior to seeing me, he had a hospitalization for rhabdomyolysis with a creatine kinase (CK) level over 20,000; those records were not available.
Presentation and examination
The patient presented to the Rush Neuromuscular Clinic with symptoms of progressive weakness, shortness of breath and dysphagia over the past five months.
His exam was notable for a thin, cachectic elderly male seated in a wheelchair. Muscle bulk was generally decreased, and contractures were present at the elbows and knees. He had severe proximal muscle weakness in his bilateral upper and lower extremities, as well as weak neck flexion, sniff, cough and voice, and nasal dysarthria and areflexia. Vibration sensation was reduced in the feet.
Based on this patient’s history, symptoms, distribution of weakness, reported history of rhabdomyolysis and degree of creatine kinase elevation, the primary diagnosis was myopathy and likely a statin-induced necrotizing autoimmune myopathy.
Motor neuron disease for this patient was less likely due to the relative rapid progression and with the self-reported CK of over 20,000. The decreased vibratory sensation was likely related to a superimposed polyneuropathy due to nutritional deficiency or prior history of alcohol use. While in the office, the patient experienced a brief episode of unresponsiveness, suspected to be a vasovagal episode with syncope triggered by pain while seated in his wheelchair. I sent him to the emergency department for urgent evaluation, including EKG and chest X-ray, to assess for a possible cardiopulmonary event.
Testing and Treatment
Once the patient was admitted to Rush, testing included an EMG that showed evidence of severe myopathy with irritative features, and treatment with intravenous immune globulin (IVIg) and IV steroids was initiated. A blood test showed the presence of anti-HMGCoA reductase (HMGCR) antibody confirming the clinical impression of a statin-induced autoimmune myopathy.
For seven months, the patient received additional infusions of IVIg therapy along with oral steroids, physical and occupational therapy.
Outcome
The patient was discharged from Rush after his initial course of treatment to a skilled nursing facility with rehabilitation therapy. He reported feeling stronger, and his CK levels gradually decreased. He was to continue receiving monthly IVIg therapy for seven months.
During a follow-up clinic visit, three months after hospital discharge, he had no shortness of breath, orthopnea or dysphagia. He was able to transfer to his bed and wheelchair independently and could stand one to -two minutes by himself. Leg strength remained his biggest issue, and he received another course of IVIG treatment, continued steroids and received physical and occupational therapy at home.
A year and a half after the initial visit to Rush’s Neuromuscular Clinic, the patient’s proximal muscle strength was normal except for mild residual weakness with right hip flexion. He is maintained on low-dose oral steroid treatment and can walk independently without an assistive device.
Analysis
Statin-induced autoimmune necrotizing myopathy can be treated.
The condition is rare. However, when present, statin-induced autoimmune necrotizing myopathy can cause significant disability for patients, with severe weakness and potentially, life-threatening rhabdomyolysis.
Early recognition of the clinical presentation and use of key diagnostic tests to make a diagnosis is critical. It is important to determine the difference between self-limited statin myotoxicity in which the HMGCR antibody is not present. Once a diagnosis of autoimmune necrotizing myopathy is made, it’s equally important to start immunosuppressive therapy early.
Individual treatment response may vary and generally requires combination immunotherapy with vigilant follow-up. Clinical remission can be achieved, often with the use of maintenance medication. And, as with any chronic condition, it’s important to educate patients about necrotizing myopathy so they are attuned to its symptoms and know when to see their provider for interval care.
