Social Determinants of Health and the Reasons Behind Missed Diagnosis and Misdiagnosis of Myasthenia Gravis

Judith Thompson, PharmD, MPH, CPHQ

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by weakness and rapid fatigue of the voluntary muscles. It is caused by an abnormal immune response that interferes with the communication between nerves and muscles, primarily at the neuromuscular junction–the area where nerve cells connect with the muscles they control. Early diagnosis of generalized MG may help alleviate some of these symptoms and ultimately improve function; however, establishing a diagnosis can be difficult due to the variation in symptom presentation.
At the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, a poster presentation found that social determinants risk contributes to MG diagnosis delays. Using IQVIA LAAD insurance claims, high-risk economic, digital landscape, and social connectedness ZIP codes were associated with elevated (but non-significant) odds for delayed diagnosis. Individuals in communities with high-risk housing (OR, 1.22) and poor health literacy (OR, 1.21) had meaningful elevated odds.

An additional study also aimed to determine if social determinants of health are associated with misdiagnosis in MG. All told, 425 (11.0%) individuals had evidence of misdiagnosis, with stroke (5.5%), followed by chronic obstructive pulmonary disease (4.5%), chronic fatigue (2.2%), Graves’ disease (1.5%), multiple sclerosis (1.4%), and Guillain-Barré syndrome (1.1%) as the most common condition. Overall, 6 high-risk social determinants of health measures had an elevated unadjusted OR for misdiagnosis, with the highest OR for social connectedness (1.40) and housing risk (1.24).

During the meeting, Judith Thompson, PharmD, MPH, CPHQ, lead investigator of both studies, sat down to discuss the data, and the significance of social determinants of health in MG diagnosis. Thompson, rare disease population health strategy lead at UCB, also described the challenges for non-specialists in recognizing MG due its fluctuating symptoms and the rarity of the disease, which limits exposure and education among primary care providers. Additionally, the conversation touched on common misdiagnosis for MG, such as stroke, chronic obstructive pulmonary disease, and multiple sclerosis, which can delay proper diagnosis for months.

NeurologyLive: Can you provide a little bit more context on the findings that you observed for our clinical audience?

Judith Thompson, PharmD, MPH, CPHQ: We conducted a retrospective analysis using an open claims data set (IQVIA) and cross-matched it with two databases detailing social risk. One of these was a census-based data set, the Area Health Resources File, and the other was a proprietary database we licensed that provides a five-point scale risk assessment based on geography. We matched these using the zip code of the most frequently visited primary care provider to assess each MG patient’s level of social risk.

What we found was that individuals with MG who received a delayed diagnosis were more likely to live in areas with poor health literacy and high-risk housing. For this study, we defined delayed diagnosis as cases where patients had symptoms or procedures suggestive of MG but did not receive an MG diagnosis within 90 days of initial presentation. We also found that individuals with MG who were misdiagnosed were more likely to live in areas with high risk for social isolation, lacking social support from services, networks of friends and family, or social groups, whether online or in person. They also faced high housing insecurity and were in the lowest income quintile. For this study, misdiagnosis was defined as cases that received an alternative diagnosis before an MG diagnosis, with no claim evidence for that alternative diagnosis after MG was coded in the data set.

Individuals with MG receiving suboptimal treatment were more likely to live in areas with high-risk housing and poor food access. We defined suboptimal treatment in a few ways, based on feedback from neuromuscular specialists. This included initial therapy that did not involve azathioprine, an acetylcholinesterase inhibitor, or cases where patients were prescribed more than 10 mg of steroids for over six months, or more than 300 mg of azathioprine for at least 24 months, or more than 3000 mg of mycophenolate for at least 12 months. These are some of our findings, but we’re continuing to investigate in more detail and within different dimensions of diversity. We’re also looking forward to collaborating with others closer to the patient experience or those with expertise in infrastructure to address these disparities.

Are there ways to alleviate some of the negative burdens caused by social determinants of health?

That’s a great question. One of the key aspects of population health is recognizing that these issues can’t be solved in isolation; they require collaboration. We’ve learned that organizations with direct patient contact need to partner with those who have resources and funding. This includes nonprofits and advocacy groups working together with researchers, pharmaceutical companies, and healthcare systems. By pooling resources, expertise, and proximity to patients, we can work collectively to address these health disparities. No single entity has all the tools to tackle this alone.

Are there presenting symptoms of MG that fly under the radar or go less recognized?

What we’re hearing from patients is that they report symptoms to providers that may go unrecognized or unnoticed by non-specialists, especially in primary care or emergency room settings, or when they see providers other than neurologists. Patients report concerns about fatigue, mental health, and fluctuating symptoms. For example, something that feels severe one day might not be as prominent by the time of the appointment, so physical assessments may not capture the peak of their symptoms. This can make it challenging for non-specialists to accurately and promptly diagnose MG. Raising awareness among non-specialists, such as ophthalmologists, pulmonologists, speech therapists, psychologists, and primary care providers, could help them recognize typical signs of generalized MG and lead to more timely and accurate diagnoses.

For nonspecialists trying to identify patients with MG, is the education lacking, or is it more of a bandwidth issue?

I think it’s a mix of both education and workload constraints. We recently hosted a panel discussion where a provider emphasized the importance of educating medical students across all specialties to provide a baseline knowledge of generalized myasthenia gravis. This way, if they encounter these patients in the ER or other settings, they can recognize some hallmark symptoms of MG and make appropriate referrals.

Also, MG is a rare disease, so non-neuromuscular specialists may only see a few cases throughout their careers. This makes it harder to prioritize MG education for non-specialists, as they might feel that investing in learning about a rare disease isn’t practical for their practice. Additionally, the non-specific symptoms of MG further complicate its identification for those unfamiliar with it.

Are there any conditions that mirror or mimic MG? Any conditions we should be attentive to?

In our study, we found that stroke was a common misdiagnosis for generalized MG. Other frequently misdiagnosed conditions included COPD, chronic fatigue syndrome, Graves’ disease, multiple sclerosis, lupus, and ALS. We also analyzed data on which provider types tend to make these alternative diagnoses. Interestingly, over half of patients remained with an incorrect diagnosis for more than six months, further delaying an accurate and timely MG diagnosis.