Age of Onset an Important Clinical Factor in Triple-Negative MG

A new study is helping to clarify how the clinical characteristics of triple-negative myasthenia gravis (TNMG) vary, especially based on the age at which a patient experiences onset of the disease.

The report was published in Muscle & Nerve.

About 80% of cases of the autoimmune disease MG are caused by autoantibodies against the acetylcholine receptor (AChR-Ab); however, some patients’ disease is caused by autoantibodies against muscle-specific tyrosine receptor kinase (MuSK-Ab), and some patients test positive for low-density lipoprotein receptor–related protein 4 antibody (LRP4-Ab).

Patients who test negative for all 3 autoantibodies are considered to be triple negative. However, these patients are relatively understudied compared with patients with more common forms of the disease.

In this new study, investigators sought to better understand the characteristics and clinical features of people with TNMG.

The authors analyzed the cases of 106 people, looking at differences in age of diagnosis among males and females and rates of symptoms such as thymic hyperplasia and bulbar muscle weakness, both clinical characteristics common in people with TNMG. They also looked at the risk of conversion to generalized MG from the ocular form of the disease.

They said one important outcome of their analysis was a bimodal distribution in terms of age of onset. When they analyzed age of onset on a decade-by-decade basis, the 2 most common decades of life when patients received their diagnosis were 0 to 9 years and 40 to 49 years. For females, 0 to 9 years was the peak time frame of disease onset, they found. They said age appears to have implications for a patient’s prognosis.

“Juvenile-onset MG affects mainly female patients and is associated with relapse,” they wrote. “Adult early-onset MG affects mostly male patients and has a good prognosis.”

The mean age of onset was 32.4 years, a younger age than in previous reports.

In terms of symptoms, adults were more likely than younger patients to experience weakness in their limbs and bulbar muscles, while younger patients were more likely to experience relapse.

About 1 in 5 patients had thymic hyperplasia, and just 1% had thymoma. Those findings also align with previous research, the authors said.

“Therefore, we suggest that thymus evaluation is necessary for every patient with TNMG,” they wrote.

Nearly half (47.6%) of patients with adult-onset TNMG achieved complete stable remission and pharmacological remission—although patients were more likely to achieve those statuses if they were given their diagnosis as an adult. Conversely, older age appeared to make patients more likely to progress from ocular TNMG to generalized TNMG.

“Our study found that increasing age of onset was the only risk factor for the development of generalized TNMG from ocular TNMG, and most patients with ocular TNMG were younger than 50 years,” they wrote.

The investigators noted limitations to their study, including its retrospective nature. They also only included steroids and immunosuppressive therapies when considering treatment and did not assess the impact of drug doses on outcomes.

The authors concluded that their study showed that age of onset is an important factor in TNMG, and said it is essential for clinicians to consider repeat testing and more sensitive testing when patients are antibody negative.

Reference

Li W, Liu P, Cui W, et al. Clinical characteristics of anti-AChR-MuSK-LRP4 antibody-negative myasthenia gravis in China. Published online March 21, 2023. Muscle Nerve. doi:10.1002/mus.27822