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A 30-year-old African-American woman presented to the emergency department for medical assessment after becoming too weak to walk. She reported proximal muscle aches in both arms and legs, a skin rash, and widespread joint pain. She had been diagnosed with systemic lupus erythematosus (SLE) 2 weeks previously. The patient told admitting clinicians that she had become worried when her urine became dark in color, and a skin rash developed along with progressive muscle weakness, which ultimately made walking on her own impossible.

She had started treatment with a tapering dose of methylprednisolone upon diagnosis of SLE. The patient said she did not drink alcohol, nor had she sustained any injuries. A review of her current medications found that she had not been taking statins, steroids, or any other medications with myotoxic adverse effects -- such as steroids, colchicine, amiodarone, hydroxychloroquine, antimalarial medications, and antiviral therapy -- or dietary supplements, herbal preparations, or over-the-counter medications.

The patient's lupus diagnosis was based on her total score of 30 on the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus; a total score of 10 or more can be classified as SLE. She had an antinuclear antibody titer of 1:1280 on HEp-2 cells, a low platelet count, joint involvement, SLE-related kidney disease, low C3 and C4, and positive anti-double-stranded DNA antibodies using crithidia luciliae substrate.

The patient's vital signs on presentation were within normal range. A physical examination identified ulcers under her tongue and on the buccal surface of her lips, and she had several areas of hyperpigmented macular rashes on her face and extremities. She had swelling in both legs and ankles, and her motor strength in all extremities was 2/5, with proximal muscle weakness.

Laboratory analysis showed elevated creatine kinase and myoglobin. Urinalysis was consistent with 2+ proteinuria and hematuria. Myositis antigen panels were negative. The viral hepatitis panel was non-reactive, and Epstein-Barr virus IgM was negative.

Clinicians considered numerous differentials: SLE-induced myositis, SLE-induced myopathy, SLE-neuropathy, macrophage activation syndrome, anti-signal recognition particle myopathy, drug-induced myopathy, thyroid-related myopathy, sarcoidosis, and dermatomyositis.

An ultrasound of the patient's abdomen was suggestive of mild fatty liver disease. A kidney biopsy revealed acute tubular injury with increased proximal tubular cytoplasmic myoglobin stained, findings that suggested class III focal lupus nephritis. An MRI revealed interstitial edema throughout both of the patient's thighs, which clinicians considered a likely sign of myositis (Figure).

The team obtained a muscle biopsy of her quadriceps using hematoxylin and eosin. The pathology report noted an active myopathic process characterized by frequent regenerating, and necrotic muscle fibers with very sparse associated chronic lymphocytic inflammation, which suggested necrotizing myopathy and type 2 muscle atrophy. However, there was no morphologic evidence of vasculitis, and no evidence of perifascicular atrophy, which is characteristic of dermatomyositis. Based on both MRI and biopsy findings, the patient was considered to have necrotizing myopathy.

Clinicians initiated treatment with methylprednisolone 250 mg IV daily and mycophenolate mofetil 500 mg twice daily. The patient also received intravenous immune globulin for 5 days. The patient's dose of methylprednisolone was tapered during her transition to oral prednisone, which was gradually increased to 1,500 mg daily.

Over the following 2 weeks, the patient showed an improvement in muscle strength from 2/5 to 4/5 in all extremities. Levels of creatine kinase declined from 20,875 to 997 during that time; tests also revealed improvements in her erythrocyte sedimentation rate, C-reactive protein, liver enzymes, and kidney function.

On day 18 of hospitalization, the patient was discharged. She continued treatment with prednisone, which was tapered over a 4-month period. She is currently taking mycophenolate mofetil, and hydroxychloroquine was later added.

Discussion

The authors reporting this of necrotizing myopathy in a patient with recently diagnosed lupus noted that SLE frequently presents with muscle weakness and pain with a proximal distribution; biopsy generally identifies "type 2 muscle fiber atrophy with minimal inflammation and no evidence of myopathy."

SLE can affect multiple organ systems, and present with considerably varied clinical features and serologies. It is more common in women of childbearing age, with a female:male ratio of up to 13:1. SLE also has a higher in African Americans, who tend to have worse outcomes.

Muscle weakness, pain, and atrophy affecting both upper and lower limbs often causes patients to seek medical attention, the case authors noted, although weakness is not generally severe. "Muscle biopsy ... can show a broad spectrum of findings, including inflammatory myopathy, vasculitis, perifascicular atrophy, and neurogenic atrophy," they wrote.

While involvement of the musculoskeletal system in SLE is fairly rare, up to 16% of patients present with muscle involvement. "Immune-mediated necrotizing myopathy is a rare group of debilitating myopathies characterized by symmetrical proximal muscle weakness that has a subacute onset and myofiber necrosis without significant inflammation," the authors wrote.

Citing a of 64 cases of necrotizing myopathy from the South Australian Cancer Registry, the authors pointed out that an estimated 21% of patients with SLE are affected by necrotizing myopathy, which may present with muscle weakness and rhabdomyolysis. Interestingly, while this review noted that necrotizing myopathy is generally distinguished from idiopathic inflammatory myositis by dominance of myofiber necrosis, lack of mononuclear inflammatory infiltrates, and presence of antibodies to signal recognition particle, none of the included patients had antibodies to signal recognition particle, nor was there any increase in malignancy compared with the general population.

The authors explained that drug-induced myopathy was unlikely in their patient, who was taking only methylprednisolone, adding that this adverse effect would typically be seen in the context of long-term glucocorticoid therapy. Furthermore, although a biopsy confirmed muscle necrosis, there was no evidence of associated vacuolar changes and mitochondrial dysfunction.

"We should always be aware that malignancies can be associated with necrotizing myopathy, and is recommended," the authors wrote. In patients with lupus, MRI evidence of muscle involvement "is characterized by interstitial edema."

Patients with SLE-related necrotizing myopathy generally have type 2 muscle atrophy, which is considered a major cause of symptoms. As in this patient, type 2 muscle fiber atrophy in the absence of myositis confirms necrotizing myopathy, the authors said, citing that showed that type 2 muscle fiber atrophy was noted in about 87% of biopsied SLE patients, despite no evidence of significant clinical, serological, or histological differences between patient groups.

In assessing patients with SLE, the authors noted the importance of considering co-existing macrophage activation syndrome as a differential diagnosis, adding that it was less likely in this patient, "given the absence of fever, which is extremely important in the diagnosis and is further supported by the absence of hepatosplenomegaly and lymphadenopathy."

Immune-mediated necrotizing myopathies should be treated promptly, they said. Immunosuppressive therapy has been shown to improve muscle weakness.

Given the rarity of necrotizing myopathy in patients with SLE, "a high index of suspicion and careful work-up is needed to arrive at this diagnosis," the authors concluded.

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