Paradigm shift: a team has discovered that autoimmunity targeting small nerve fibers can cause chronic pain. Injections of immunoglobulins improve the pain.
A study conducted in some chronic pain syndromes secondary to small nerve fibroids 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 an autoimmune small fiber polyneuropathy (SFPN) shows that intravenous immunoglobulin treatment, used to treat other autoimmune diseases, relieves pain in 75% of patients .
A new paradigm in chronic pain
“This is the first treatment that has the potential to actually improve nerve damage, not just to block pain with drugs such as opioids or psychotropic drugs that do not treat the cause,” says Prof. Anne Louise Oaklander , director of the Department of Neurology at Massachusetts General Hospital and lead author of an article receiving an advance onlinepublication in the journal Therapeutic Advances in Neurological Disorders . “This is a proof-of-concept study that shows that immune system modulation can be effective in treating small, seemingly autoimmune nerve fibrosis, a condition most painful patients do not know. not reached “.
Achievement of small nerve fibers
This new disease consists of lesions specifically affecting the tiny nerve fibers that transmit pain signals or control the internal functions of our body such as heart rate, blood pressure and sweating (vegetative nervous system).
Patients with this condition often develop chronic pain, fatigue, standing weakness or discomfort, rapid heart rate or gastrointestinal problems.
The currently known causes of this small nerve fiber disease include diabetes, other autoimmune diseases, infections such as Lyme disease and some viruses and chemotherapy, but this article has focused on the 30 to 50% pain patients with no cause found on their first assessment leading to a diagnosis of “idiopathic” small nerve fibrosis syndrome.
Previous studies by the Oaklander group and other teams have suggested that some of these patients have underlying and undiagnosed autoimmune disease.
Autoimmune origin of pain
In a study published in 2013 in Pediatrics , the Oaklander team presented the first evidence of an autoimmune origin in some cases of syndrome of involvement of small nerve fibers in children and adolescents.
While these healthy youths had no medical explanation for their small fiber involvement, the researchers noted that many had personal or family histories of autoimmune diseases or markers of immune / inflammatory activation. These facts and other evidence led the team to propose the existence of autoimmune nerve fibrosis syndrome, a condition 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 who have also been associated with the syndrome of involvement of small nerve fibers.
Interest of intravenous gamma globulins
The Oaklander 2013 study in Pediatrics also reported that treatment with steroid drugs or immunoglobulins was able to improve 12 of the 15 children treated.
The efficacy of corticosteroids is also demonstrated in a few other publications, but their long-term use causes undesirable side effects.
The current study was conducted with intravenous immunoglobulin therapy, an approved treatment in a wide variety of immune disorders and may be prescribed off-label for other immune disorders.
A pilot study on 55 patients
The team reviewed the medical records of 55 Massachusetts General Hospital chronic pain patients who met the diagnostic criteria for small nerve fibrosis syndrome, and who had no known cause for current diagnostic procedures. These patients were treated with intravenous immunoglobulin at an initial dose of 2 grams per kilogram of weight every four weeks.
All but four have been treated for at least three months. The 4 who gave up did so because of an intolerance to immunoglobulins. The efficacy analysis of the treatment was based on nine types of validated criteria, all of which were improved: 74% of 51 patients noted that their pain and symptoms improved after treatment, as did 77% of their patients. doctors. For 8 patients, the symptoms improved so much that they were able to progressively reduce any associated treatment and eventually stop it.
A revolution in power
According to Prof. Oaklander, “Although it is not a controlled clinical trial, the results are so surprising that they are changing the paradigm in this disease because the fact that immunomodulatory therapy is also Effective is the strongest evidence that some people with chronic pain related to a 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 should now be routinely 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 that is being organized. Developing knowledge of 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 done on various exams including Sudoscan and skin biopsy to analyze the density of small nerve end fibers in the skin.