In the treatment of inflammatory muscle diseases (or myositis), which has long been hampered by their very heterogeneous nature, a new classification represents a decisive step. The result is better diagnosis and more personalized treatments for patients.
Weakness of the hands or thighs and shoulders, muscular atrophy, pain, handicap, fatigue… inflammatory diseases of the muscles, or myositis, constitute the most important group of potentially treatable diseases of the muscles. However, the very heterogeneous nature of this group of muscle diseases has long been an obstacle to their proper management, even leading to treatment errors.
The team from the Institute of Myology at the Pitié-Salpêtrière hospital in Paris has developed a new classification of these inflammatory myopathies. From now on, myositis are grouped into 4 categories that are better individualized compared to the previous classifications, according to the clinical criteria of the patients. This classification, published in the journal JAMA Neurology, and validated by the Food and Drug Administration in the USA, paves the way for improved diagnosis and treatment.
Autoimmune diseases
Myositis, or inflammatory myopathies, is a group of autoimmune diseases that specifically affect muscles. At the origin of weakness and atrophy of various muscles, these diseases are caused by a disruption of the immune system, normally responsible for protecting the body against external attacks (microbe, virus …), and which suddenly turns around against the organism (and in myositis, against the muscle).
Between 3,000 and 5,000 sick adults and children in France.
While all myositis has autoimmune involvement in common, each has its own trigger factors. Until now, the classification identified 3 types of myositis (polymyositis, dermatomyositis, inclusion myositis) according to a classification system established in 1975, updated in 2017 (ACR / EULAR criteria) and based essentially on criteria clinical and histological.
Diagnostic and Therapeutic Erruers
Prof. Olivier Benveniste and his research team (“Inflammatory myopathies and innovative targeted therapies”) from the Institute of Myology, identified serious diagnostic errors induced by this old classification, which is both incomplete and non-homogeneous.
These diagnostic difficulties are serious because they can be the source of errors in treatment. Thus, certain patients, wrongly identified as “inclusion myositis”, have thus been treated with high doses of corticosteroids, whereas the latter clearly aggravate this type of myopathy.
A new cluster analysis
A study on 260 patients was therefore set up to analyze the clinical characteristics and the autoantibodies, which can be causes, but also consequences of the disease.
Thanks to innovative statistical methods which make it possible to automatically group together patients who resemble each other (cluster analysis), it was possible to identify 4 main types of myositis: “inclusion myositis”, “dermatomyositis”, “self-necrotizing myopathy”. immune ”and“ anti-synthetase syndrome ”. From now on, “polymyositis” no longer constitutes a type of myositis as such and disappears from the classification.
Individualization of treatment
This new classification is decisive for making a more precise diagnosis and offering patients a more suitable treatment.
“Our goal was therefore to define a classification based on criteria that are both phenotypic, biological and immunological in order to be able to better individualize the different types of myositis and ultimately to find suitable treatments for patients.
This new classification is becoming a benchmark since even the FDA, which until then used the American classification, recommends basing it on our work, ”explains Prof. Benveniste, from the Institute of Myology at the Pitié-Salpêtrière hospital in Paris. .
A new classification into 4 types of myositis
Inclusion myositis
This myositis more often affects men over 60 years old. It is slowly progressive but ultimately causes a very disabling motor deficit.
It affects more particularly the muscles of the thighs (which are used to climb the stairs, get up from a chair, to be stable when walking), the quadriceps, the muscles which are used to close and tighten the hands and the muscles of swallowing. The diagnosis is made by histological examination.
This myositis is resistant to conventional treatments such as corticosteroids. It is due to the presence in the muscle of both an inflammatory reaction (myositis) and a neurodegenerative process, similar to Alzheimer’s disease (with inclusions).
Dermatomyositis
This form affects women more often, but also children, and is accompanied by damage to the skin. A risk of cancer appears in the oldest patients (generally after 60 years).
Apart from myositis which leads to muscle weakness predominantly in the shoulders, this disease is characterized by the presence of typical dermatological lesions (erythema of the eyelids and of the extension faces of certain joints). The specific antibodies for dermatomyositis are anti-Mi2, anti-SAE, anti-NXP2, or anti-TIF1gamma.
This disease is caused by an imbalance in the immune system involving type 1 interferon, which normally allows it to defend itself against viruses. New treatments specifically targeting this interferon pathway are under development.
Autoimmune necrotizing myopathy
It consists of a purely muscular attack affecting patients of all ages.
This is myositis which, if left untreated, leads to the most severe and disabling muscle atrophy. It is linked to the presence of two specific antibodies, anti-SRP or anti-HMGCR, which directly attack and destroy muscles. Anti-HMGCR drugs can appear after taking statins.
The treatment here aims to eliminate these antibodies which are directly pathogenic, while waiting to find the cause of the production of these antibodies.
Anti-synthetase syndrome
It is a general disease which affects the muscles but also the joints (chronic inflammatory rheumatism), as well as the lungs (with shortness of breath which can be severe at the stage of pulmonary fibrosis).
Here too, certain antibodies seem to be directly involved in the lesions of the disease: anti-Jo1, anti-PL7 or anti-PL12 (other autoantibodies are also described).
The treatment is immunosuppressive and based on a combination of corticosteroids and methotrexate or azathioprine, being aware that there are few clinical trials on this disease.
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