Paradigm shift: a team has just discovered that autoimmunity targeting small nerve fibers can cause chronic pain. Immunoglobulin injections improve pain.
A study carried out in certain chronic pain syndromes secondary to damage to small terminal nerve fibers shows that some of these cases are caused by an autoimmune disease. The study also offers the first effective treatment option for this syndrome.
This pilot study of 55 patients diagnosed with what appears to be autoimmune small fiber polyneuropathy (SFPN) shows that intravenous immunoglobulin therapy, used to treat other autoimmune diseases, relieves pain in 75% of patients .
A new paradigm in chronic pain
“It is the first treatment that has the potential to really improve nerve damage, and not just block the pain with drugs such as opioids or psychotropic drugs that do not treat the cause” explains Prof. Anne Louise Oaklander , head of the department of neurology at Massachusetts General Hospital and lead author of an article receiving a publication anticipated online in the journal Therapeutic Advances in Neurological Disorders. “This is a proof of concept study which shows that modulation of the immune system can be effective in treating damage to small nerve fibers apparently of autoimmune origin, a disease that most pain sufferers are not aware of. not achieved ”.
Small nerve fibers damage
This new disease consists of lesions specifically affecting the tiny nerve fibers that transmit pain signals or control internal body functions such as heart rate, blood pressure and sweating (vegetative nervous systems).
Patients with it often develop chronic pain, fatigue, weakness or discomfort when standing, a rapid heart rate, or gastrointestinal problems.
Currently known causes of this small nerve fiber disease include diabetes, other autoimmune diseases, infections like Lyme disease and certain viruses, and chemotherapy, but this article has focused on the 30-50% patients with pain in whom no cause was found on their first evaluation, leading to a diagnosis of “idiopathic” small nerve fiber syndrome.
Previous studies by the Oaklander group and other teams have suggested that some of these patients have underlying, undiagnosed autoimmune disease.
Autoimmune origin of pain
In a study published in 2013 in Pediatrics, the Oaklander team had presented the first evidence of an autoimmune origin in certain cases of small nerve fiber syndrome in children and adolescents.
While these healthy young people had no medical explanation for their small fiber impairment, the researchers noted that many had a personal or family history of autoimmune disease or markers of immune / inflammatory activation. These facts and other evidence led the team to suggest the existence of small nerve fiber damage syndrome of autoimmune origin, a disease in which the immune system directly attacks small nerve fibers.
Several other types of nerve damage caused by autoimmune attacks are already known: against nerve roots in Guillain-Barré syndrome or against large nerve fibers in systemic autoimmune diseases such as rheumatoid arthritis and lupus, diseases which have also been associated with the syndrome of small nerve fibers.
Benefits of intravenous gamma globulins
The 2013 Oaklander study in Pediatrics also reported that treatment with steroid drugs or immunoglobulins was able to improve 12 of the 15 children treated.
The effectiveness of corticosteroids is also shown in a few other publications, but their long-term use causes unwanted side effects.
The current study was performed with intravenous immunoglobulin therapy, a treatment approved for a wide variety of immune disorders and which may be prescribed off-label for other immune diseases.
A pilot study on 55 patients
The team reviewed the medical records of 55 chronic pain patients at Massachusetts General Hospital who met the diagnostic criteria for small nerve fiber syndrome, and had no known cause based on current diagnostic methods. These patients were treated with intravenous immunoglobulins at an initial dose of 2 grams per kilogram of body weight every four weeks.
All but four were treated for at least three months. The 4 who dropped out did so because of immunoglobulin intolerance. The analysis of the effectiveness of the treatment was based on nine types of validated criteria, which were all improved: 74% of the 51 patients noted that their pain and symptoms improved after treatment, as did 77% of their doctors. For 8 patients, the symptoms improved so much that they were able to gradually decrease any associated treatment and eventually stop it.
A revolution in power
According to Prof. Oaklander, “Although this is not a controlled clinical trial, the results are so surprising that they are changing the paradigm in this disease because the fact that an immunomodulatory treatment is also effective is the strongest evidence that some people with chronic pain associated with small fiber syndrome have an autoimmune cause that can be treated.
Although immunotherapy is not indicated for all pain syndromes with involvement of small nerve fibers, those with an idiopathic form must now be systematically screened for all known causes, as well as for an autoimmune cause and discuss immunoglobulins. intravenous.
This pilot study must be validated in a prospective and controlled clinical trial which is currently being organized. Developing knowledge about the still unknown autoimmune cause that affects certain small nerve fibers should lead to the identification of more precise immunological mechanisms and lead to less expensive and more manageable immunotherapies than intravenous immunoglobulin. In France, the diagnosis of chronic pain syndrome related to lesions of small nerve fibers can be made on various examinations including Sudoscan and skin biopsy to analyze the density of small terminal nerve fibers in the skin.
Reference site on neurological pain:
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