Systemic sclerosis is one of the most severe autoimmune rheumatic diseases. In people with this condition, mortality is approximately 3.5 times higher than among healthy people of the same age.
Despite the seriousness of the disease, it remains relatively understudied, particularly with regard to various aspects of complications. For this reason, rheumatologist Kristīne Ivanova focused in her doctoral dissertation Systemic Sclerosis in Latvia: Patient Characteristics, Peripheral Nervous System Involvement and New Biomarkers on this group of patients, who often lack both scientific attention and practical solutions.
For the first time in Latvia, the study systematically assessed the prevalence of the disease, identifying approximately 84 cases per million inhabitants. This figure is lower than in many parts of Europe, but, as the researcher emphasises, it may indicate not a lower incidence of the disease, but rather insufficient diagnosis.
How to Study a Complex Disease?
The study used a nationwide approach, analysing data from both of Latvia’s clinical university hospitals, where almost all patients with this disease are concentrated. In total, 159 patients who met the specified criteria were identified, and 103 of them agreed to undergo more in-depth examination.
To gain as comprehensive an understanding as possible of how systemic sclerosis manifests in Latvian patients, the physician combined different sources of information and examinations. First, data on the course of the disease, organ damage, and treatment were collected. The patients were then assessed for skin changes, as well as the condition of the lungs, heart, and digestive system. Blood tests were also carried out, including testing for autoantibodies and potential biomarkers. Particular attention was paid to the nervous system, as the researcher wanted to determine how often patients experience nerve damage and how it affects their well-being. Several methods were used for this purpose – nerve conduction studies, sensory tests, patient questionnaires, and pain assessment scales. In addition, metabolic changes in the blood were analysed by comparing patients with and without nerve damage. This combined approach made it possible not only to describe the disease, but also to investigate its mechanisms and early indicators.
When Pain Indicates Nerve Damage
Although systemic sclerosis has traditionally been associated with damage to the skin and internal organs, the study highlighted an important and previously underestimated aspect – involvement of the nervous system.
It was found that large-fibre neuropathy – damage to the nerve fibres responsible for movement and the sensations of touch and vibration – occurs in 43% of patients. Small-fibre neuropathy, meanwhile, affects the smaller nerve fibres that help perceive pain, heat, cold, burning, or tingling, and it may also be present in patients whose conventional nerve tests are still normal. Overall, this means that nerve damage in patients with systemic sclerosis may be much more common than previously thought.
“The surprising finding was how many patients had polyneuropathy,” notes K. Ivanova. Polyneuropathy means that not just one individual nerve is damaged, but several nerves at the same time, most often on both sides of the body. It often manifests in what is known as a glove-and-stocking pattern – with tingling and sensations of coldness.
Earlier Detection, More Precise Help
The study also identified potential diagnostic tools for the future. Patients with nerve damage had elevated levels of several biomarkers in their blood, including NfL, or neurofilament light chain, GFAP, and GDF-15. This suggests that such blood-based indicators could in the future help identify earlier those patients who need more in-depth examinations of the nervous system. In addition, metabolomic analysis showed that patients with neuropathy develop a different biochemical profile, for example, elevated kynurenine levels and changes in amino acid metabolism. These changes may be associated with neurotoxicity, oxidative stress, and impaired mitochondrial function.
For patients, this means an opportunity to explain pain and other complaints more precisely, which until now may have been attributed mainly to skin changes.
“If the pain appears neuropathic, it should not immediately be attributed solely to skin changes – nerve damage should be investigated,” emphasises K. Ivanova.
In practical terms, this means paying greater attention to specific symptoms, using more targeted diagnostics, and creating opportunities to personalise treatment in the future. At the same time, it must be acknowledged that medicine is not yet able to completely stop the progression of this damage, and existing neuropathic pain often persists – it cannot always be significantly reduced. This is precisely why early detection and timely care are especially important in order to preserve patients’ quality of life as much as possible.
Towards Earlier Diagnosis and Better Care
After defending her doctoral dissertation, K. Ivanova plans to continue the research direction she has begun, focusing in particular on nervous system involvement in patients with systemic sclerosis. The study has already shown that damage to large nerve fibres is more common in this patient group than previously thought, but this is only part of a broader issue. The next step could be to investigate small-fibre neuropathy and the autonomic nervous system. The researcher believes that findings in this area could be even more surprising.
In the future, K. Ivanova also intends to focus on other complications of systemic sclerosis, including involvement of the digestive system. Some of these changes can also be detected in Latvia, but for patients this often means a long, complicated, and sometimes financially burdensome path to obtaining the necessary examinations. Therefore, one of the future goals is not only to demonstrate that these complications exist, but also to find ways to diagnose them more quickly and accessibly for patients.
Thus, rather than bringing the research to a close, this study opens the way to a broader understanding of a disease that can affect much more than the skin and internal organs. It highlights the need for a multidisciplinary approach, closer cooperation between rheumatologists, neurologists, and other specialists, as well as practical solutions that would help patients receive an accurate diagnosis and appropriate care more quickly.
