Having a rare disease can feel overwhelming. But having a rare form of a rare disease – making you the “rare of the rare” – is a particularly lonely struggle.
Many people with seronegative myasthenia gravis face this experience. These patients – roughly 10% of those diagnosed with MG – do not have detectable anti-AChR or anti-MuSK autoantibodies in their blood. These are the two antibodies known to cause MG symptoms.
As the science progresses, some seronegative patients have been found to have proteins such as agrin or a different antibody, anti-LRP4, causing their symptoms, but for many others the exact cause remains elusive.
Because their myasthenia isn’t diagnosable with a blood test, seronegative MG patients often go longer without an accurate diagnosis, even with typical MG symptoms such as eye drooping, double vision, shortness of breath, and difficulty chewing and swallowing.
The quest for answers – and relief from symptoms – can take months or years.
“In the earlier phases of my symptoms, it was not easy to put the pieces of the puzzle together,” says Cheri Heitman-Higgason, a former nurse who was diagnosed with seronegative MG in 2015 after a long diagnostic journey. She was tested for anti-AChR and MuSK autoantibodies, underwent repetitive nerve stimulation and single fiber EMG testing, and was finally diagnosed with MG after traveling to see an MG specialist.
Cheri and others with seronegative MG talk about the pitfalls of this process, from working with insurance to get approvals for tests to being misdiagnosed with anxiety or a psychiatric disorder. The process leaves many feeling defeated.
“Seronegative MG exists and has the same symptoms as antibody positive MG,” says Cheri. “When we are not seen or heard, it can be very dehumanizing.”
Her comments are echoed by others in online support groups, articles, and social media posts, where patients find they share similar stories:
“MG is rare. But being seronegative MG is even more rare. Our fight for recognition and treatment is that much harder. We don’t all present the same way, and the disease fluctuates throughout the day.”
“Don't assume just by looking at us on the outside that nothing is wrong. We aren't making it up.”
“Seronegative MG needs much more awareness!”
Delay in Treatment
A delay in diagnosis leads to a delay in treatment, especially adequate treatment. Patients go without adequate treatment face clinically worse outcomes. A recent study demonstrated that people with MG who received early, fast-acting treatment within six months of symptoms fared better than those whose treatment was deferred.
Cheri notes her treatment plan, including a noninvasive ventilator, helps her breathe. Without a diagnosis, she wouldn’t have access to these life-saving interventions.
“This is so important to my daily life, but without a diagnosis, it is not available to us,” she says.
Seronegative MG patients also do not have access to many of the newer medications, which are only FDA-approved for people with anti-AChR or anti-MuSK antibodies.
“As a friend says, we are fighting the same war as other MG patients without the same arsenal of treatments,” says Cheri. “I would like to see a day where those with seronegative MG are able to get diagnosed earlier and be treated earlier and more adequately, before they lose years of better quality of life and their careers like I and so many others have.”
As awareness of seronegative MG grows, more people are likely to receive accurate diagnoses and receive the help they need. Research is also growing in this important area, with experts exploring other proteins and antibodies that may cause symptoms. With that knowledge, additional testing can be developed, as well as better treatments for all MG patients.
Advice for Others
Having journeyed so far and experienced so much on her path to diagnosis and proper treatment, Cheri offers this advice others:
- Never give up!
- Make sure you have had all the testing: AcHR, MuSK, LRP4, repetitive nerve stimulation, single-fiber electromyography (SFEMG), and chest CT (to name a few) and that you obtain and keep a record of all results. If your condition allows, having blood testing and EMG testing done prior to starting immunosuppressant medications or disease modifying treatments – which could potentially alter the antibodies in your blood – eliminates the possibility of such treatments interfering with test results.
- Discuss testing for other rare diseases with your provider. Many rare diseases have similar symptoms but different treatments. Other rare diseases, including LEMS and CMS, can be diagnosed with additional labs, genetic testing, imaging like MRI of the brain and spine, lumbar puncture, etc.
- Be open to other possibilities in order to make every attempt to get to the root of the problem, whatever it may be. Try to find a physician who will work with you.
- Remember not to demand a diagnosis, but work together with your provider.
- If a provider is not working out, getting another opinion is often more helpful. I have not found assistance from anyone who originally discounted me.
- Be open-minded with your new provider. Go to the appointment prepared with a list of questions and concerns. A fresh perspective can help you get a diagnosis.
- Since symptoms with MG are variable, document your symptoms clearly and include aggravating and alleviating factors. Use of a written diary as well as photos and videos may be helpful.
- And again, as difficult as it is, NEVER GIVE UP. I wish it were not so difficult. But believe in yourself and keep going until you find the answers you need.
Read more about Cheri’s patient journey in her article on Myasthenia-Gravis.com.
Don’t let your seronegative MG be a lonely struggle!