Myasthenia gravis affects at least three times more people in Sardinia than elsewhere.

It's called Myasthenia Gravis (MG), or simply Myasthenia: it's a rare disease, but like other immune-mediated disorders, it has a particularly high incidence in Sardinia. Worldwide, it affects an average of 20 people per 100,000 inhabitants, but in Sardinia the numbers are much higher, almost three times the European average, with a prevalence of 55.3 cases per 100,000—the highest known in the world.

These figures emerge from a study published in 2019 by the University of Sassari, and according to these data, there are approximately 1,000 affected people on the island. Myasthenia gravis is an autoimmune, non-hereditary disease with an unpredictable course. Symptoms can vary from person to person, but it is often debilitating and has a significant impact on quality of life. It is triggered by the abnormal production of various antibodies that attack the neuromuscular junctions, causing general muscle weakness that can affect the eyes, arms, and legs, but can also make swallowing and chewing impossible, and can even lead to respiratory distress.

This disease and its impact on the island were discussed at the conference "Myasthenia Gravis, Sardinia at the Center," organized by the Osservatorio Malattie Rare (OMaR) with the patronage of Aim-Associazione Italiana Miastenia e Malattie Immunodegenerative Amici del Besta, Sardinia section. Moderated by OMaR director Ilaria Ciancaleoni Bartoli , the conference focused on the current situation, the organization of the network and its pathways, and the needs of patients.

The difficulty of tracking all patients

"The regional chapter of AIM-Associazione Italiana Myasthenia is working to map the challenges facing our region, which exist but can be addressed through the collaboration of clinicians and institutions," said Maya Uccheddu , coordinator of AIM Sud Sardegna. "First of all, it would be helpful to have actual patient numbers across Sardinia: we know that many patients are likely not tracked because they are being treated outside the region or in peripheral centers, which cannot grant exemptions. But the numbers are also essential for understanding the regional distribution and for planning. Myasthenia is a disabling disease, and often, even with treatment, fluctuating symptoms remain or unexpected relapses occur. The social and economic impact is significant, often resulting in loss or reduction in working hours for the affected person, but also for the caregiver. As for the network of regional reference centers, it may be necessary to add to it: we are happy that it has been recently reorganized, but by working on the mapping, we are verifying that some important centers that actually provide excellent service to patients have been left out."

The requests made by clinicians and patients can therefore be summarised as follows:

1. Inform the population about the disease, so that patients no longer feel 'invisible';
2. Raise awareness among the entire medical profession about the symptoms to facilitate a faster diagnosis;
3. Strengthen the sickness registry, thus promoting organization and economic planning;
4. Integrate and strengthen the Regional Network of Reference Centers.

The conference was attended by a broad institutional representation: Armando Bartolazzi, Councillor for Hygiene and Health; Paolo Serra, Director of the new Ares 'Drug Hub'; Carla Fundoni, President of the Sixth Health Commission; and Ivan Piras, Regional Councillor of the same Commission.

A debilitating disease

"Myasthenia gravis is a severely disabling disease," explained Federica Basciu , coordinator of Aim Nord Sardegna, "which leaves you unable to perform daily activities: working, caring for your family, or even just combing your hair or brushing your teeth. Sometimes, however, it also makes you misunderstood: because it's a disease with no obvious signs and symptoms: those who suffer from it, like me, don't look like they're sick. People with myasthenia gravis often lose their jobs, are almost never granted Law 104, and don't have access to social assistance benefits such as disability insurance. For this reason, we must educate the public, through the media and public decision-makers, about the difficulties and needs of those affected."

The difficulty of diagnosis

"Due to the variability of symptoms, immediately recognizing MG is not always easy, and diagnoses sometimes still arrive too late," explains Dr. Francesca Pili , a neurophysiologist at the Duilio Casula University Hospital of Monserrato (Cagliari). "This happens especially if the person showing symptoms isn't immediately referred to a referral center and begins to bounce from one specialist to another. This is why it's important to increasingly discuss myasthenia gravis in different contexts, so that even non-specialist doctors can recognize and recognize certain warning signs and refer patients to referral centers, which also exist here in Sardinia, and which can also issue exemptions for rare diseases. Unfortunately, even today, many people seek treatment outside the island because there is little awareness of our network, which certainly has weaknesses but is improving."

The new therapies

"Today," added Davide Manca , neurologist in the Neurology Division of the G. Brotzu Hospital in Cagliari, "traditional therapies are being combined with new drugs with specific mechanisms of action that allow us to treat refractory forms of the disease and significantly reduce the side effects of long-term immunosuppressive therapy. Achieving these goals requires early diagnosis, regional organization and planning, with a network of qualified referral centers that offer concrete diagnostic options and the most personalized treatment path possible."

"Our study, which considered cases of Mg positive for anti-AChR and/or anti-MuSK autoantibodies, shows that the prevalence of the disease is steadily increasing, likely due to the increased availability of antibody diagnostic tests and greater awareness among clinicians," explained Elia Sechi , a neurologist at the Neurological Clinic of Sassari, a specialist in autoimmune neurological diseases and first author of the scientific publication. "Most cases occur after age 50, especially among men, although the disease can occur at any age. We estimate that approximately 1,000 patients are affected on the island, with a significant impact on their social, health, family, and work lives."

"It's now known that Sardinia has a relatively isolated population, with unique genetic roots. This could contribute to the population's susceptibility to autoimmune diseases such as myasthenia gravis ," added Paolo Solla , director of the Neurology Clinic at the AOU Sassari. "We also see this increased incidence for other immune-mediated diseases such as multiple sclerosis or type 1 diabetes." Although approximately 1,000 patients are expected on the island, the Regional Center for Rare Diseases registers just under 500, a gap likely caused by the fact that the Regional Registry was activated in 2017, which could mean it's missing patients diagnosed much earlier.

"This is not surprising; it's highly likely that patients diagnosed many years ago were not included, and a significant portion of those who routinely seek treatment outside the region may also be missing," explains Paolo Tacconi , a neurologist at ASL 8 in Cagliari, who has historically treated this condition on the island. "Furthermore, the registry is implemented based on the exemption code, and not all patients request it, perhaps because they are already exempt due to other disabilities or income, or perhaps because they are referred to peripheral centers that cannot grant exemptions. It would be truly important to strengthen the registry and, with the support of the institutions, find a simple mechanism to reveal the true number." In the Nuoro area, the caseload is extremely high and there is a high percentage of family history. There are actually clusters, in towns where the incidence is high, such as Fonni and Sarule. Nicola Carboni , neurologist at San Francesco Hospital in Nuoro, finally spoke out for the request for a specific PDTA for myasthenia gravis and for the "need to make the network more efficient and effective, promoting excellence and strengthening centers that are most understaffed with professionals in order to manage patients uniformly across the entire region."