Myositis-specific antibodies a ‘powerful tool’ for diagnosis, management
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DESTIN, Fla. — Understanding which autoantibodies are present in patients with myositis can help with both diagnosis and treatment, according to a presenter at the 2023 Congress of Clinical Rheumatology-East.
“Myositis-specific autoantibodies define unique clinical phenotypes,” Julie Jisun Paik, MS, MHS, associate professor of medicine in the division of rheumatology at the Johns Hopkins University School of Medicine, and director of clinical trials at the Johns Hopkins Myositis Center, told attendees. “They can be a powerful tool in diagnosis and prognosis. They can also guide therapeutic management.”
Paik described several antibodies that can be found in dermatomyositis patients, including TIF1 gamma, NXP2, MDA5, anti-SAE, anti-synthetase, PL-12 and PL-7.
“TIF1-gamma is really tightly linked with cancer risk,” she said. “There is a high risk, but it is not everybody.”
Specifically, patients with CCAR1 antibodies plus TIF1 were most likely to develop malignancy, according to Paik.
Regarding clinical presentation in patients with TIF1 gamma, Paik noted that they demonstrate more extensive skin disease but are less likely to present with arthritis, Raynaud’s phenomenon or interstitial lung disease.
“But if patients have refractory disease, malignancy screening or CT scan of the chest, abdomen or pelvis is recommended,” Paik said.
Whole-body PET-CT may also be necessary.
“NXP-2 autoantibodies are very classically associated with calcinosis,” Paik added.
This calcinosis is more common in children and can be notoriously difficult to treat in this patient population, but adults may also experience it. Children are generally treated more aggressively, and, accordingly, the calcinosis can recede. However, this manifestation may not be on the radar of many rheumatologists treating adults. Paik encouraged attendees to look closer if patients are describing “hard rocks” on the skin of the buttocks or upper legs.
MDA-5 associated dermatomyositis, meanwhile, is marked by dorsal cutaneous ulcers and so-called “kissing papules,” according to Paik. Patients with MDA-5 antibodies may also present with polyarthritis.
“These ulcers are extremely difficult to treat,” Paik said. “They often get infected.”
Anti-SAE antibodies are antibodies to the small ubiquitin-like modifier activating enzyme. It manifests as recalcitrant skin or tenosynovitis, it can be amyopathic or hypomyopathic, and there are commonly pulmonary nodules present. Co-incident cancer may also occur, according to Paik. Rapidly progressing ILD has been observed in these patients, along with pneumonia and skin necrosis.
“There may be a lot more data emerging about SAE antibodies and cancer risk,” Paik said.
Anti-synthetase syndrome can involve several autoantibodies, the most common of which are Jo-1, PL-7 and PL12.
“Usually, the clinical presentation or phenotype is that you present with one single feature first, like myositis, ILD or arthritis,” Paik said.
Regarding anti-PL-12 and PL-7 antibodies in the anti-synthetase setting, she suggested that African American patients with these antibodies are more likely to have more severe disease. Conversely, white patients with anti-synthetase syndrome are more likely to demonstrate anti-Jo-1 antibodies. Patients with PL-12 and PL-7 have more lung function complications, according to Paik.
Signal recognition particle (SRP) immune-mediated necrotizing myopathy is also more common in African American populations. It is marked by early fatty infiltration.
“(Patients) can look just like a child with muscular dystrophy,” Paik said. “It is really awful to see.”
Patients with SRP often experience manifestations in the hamstrings and abductor magnus. These patients should be treated aggressively, according to Paik.
“We throw almost everything at them because we do not want them to be really debilitated,” she said.
For patients with inclusion body myositis (IBM), the anti-NT5C1A antibody is abnormally distributed in the muscle, according to Paik.
“It localizes to areas of myonuclear degeneration,” she said.
Meanwhile, patients with NT5C1A can experience rimmed vacuoles and are marked by more distal weakness than proximal weakness. The weakest muscles are usually the finger flexors and knee extensors, Paik added.
For patients who are positive for U3-RNP antibodies, Paik offered a waring.
“Please do not forget about these patients who can get severe diffuse scleroderma,” she said.
African American patients are more likely to demonstrate U3-RNP antibodies. These patients can present with early onset pulmonary hypertension, skeletal myopathy or severe gastrointestinal disease.
The spectrum of anti-Ku antibodies is “very heterogeneous,” according to Paik.
“These patients will have more muscle involvement at presentation or at follow-up,” she said. “But there is not as much skin disease or dermatomyositis.”
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Paik J. How can autoantibodies in myositis predict prognosis? Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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