Autoimmune diseases and endometriosis: study proves a connection

Endometriosis is commonly defined as a chronic gynecological disease affecting up to 15 percent of women of childbearing age [1]. For a long time, it was assumed that the disease only affected the abdominal cavity, and in most cases only the small pelvis. However, based on recent studies, there is much to suggest that it is a systemic disease [2]. Even though the causes of endometriosis have not been conclusively clarified to date, abnormalities in the immune system are evident in women suffering from endometriosis. A meta-analysis has therefore investigated the relationship between endometriosis and autoimmune diseases [3]. Even if the existing studies still need to be supplemented by further, more concrete studies, there is much to suggest that there is a close connection between endometriosis and the immune system.

Symptoms of endometriosis: more than cycle-dependent pain

Endometriosis is a benign disease in which cell clusters that actually only occur inside the uterus also grow outside the uterus [4]. These cell clusters are called endometriosis lesions because they are structurally similar to the endometrium, the lining of the uterus. These endometriosis foci can occur in different areas: In the muscular layers of the uterine wall, on the vagina but also on the peritoneum, urinary bladder and ureter. Likewise, the intestines, lungs, liver and skin scars can be affected.

Symptoms classically associated with endometriosis are cycle-related lower abdominal pain that can also radiate to the back and legs. Endometriosis is also among the causes of decreased fertility or infertility [5]. However, recent studies have shown that systemic inflammatory reactions and increased pain sensitization also occur in the context of endometriosis [6]. A link between endometriosis and rheumatoid arthritis [7] has also been demonstrated in a recent study.

Getting to the bottom of endometriosis: Causes and risk factors for the development of the disease

The exact causes of endometriosis have not been conclusively clarified to date. There are several theories, but none of them can explain all facets of the disease [8]. Therefore, experts now believe that the cause of endometriosis is to be found in a combination of hormonal, immunological, anatomical and (epi-)genetic factors.

The most important theories on the development of endometriosis include:

• Retrograde menstruation theory: adherents of this theory believe that edometrial cells enter the abdominal cavity via the fallopian tubes during menstruation.
• Coelomic metaplasia theory: according to this theory, the structures of the endometriosis lesions develop from cells in the peritoneum (peritoneum), pleura (pleura of the chest/ribs) and ovaries (ovaries).
• Stem cell theory: according to this theory, stem cells from the bone marrow are considered to be causative for the development of endometriosis lesions.
• Lymphatic/vascular benign metastasis theory: According to this theory, endometriosis tissue is transported from the uterus to other regions of the body via the lymphatic system or blood vessels.

Endometriosis and autoimmune diseases: Overview of the study and its results

The study from 2019 is a so-called meta-study. This means that existing studies on the corresponding question were researched and specifically evaluated. The aim of the study was to find out whether, on the basis of the existing research results, it can be assumed that there is a connection between endometriosis and autoimmune diseases.

A total of 26 studies that met the guidelines were included in this meta-study. These studies proved that there is an association between the occurrence of endometriosis and autoimmune diseases. From these 26 studies, four studies were selected in a further step,

which on the one hand qualitatively meet therequirements of thestudy designs and, on the other hand, were able to demonstrate a significant (scientifically meaningful) association between endometriosis and autoimmune diseases.Across the four studies that provided confirmed results, an association between endometriosis and the following Autoimmune diseases can be detected:

• Systemic lupus erythematosus: Rheumatic disease that manifests mainly in the skin and joints, i.e., with skin redness and joint pain.
  Sjögren’s syndrome: disease of the salivary and lacrimal glands.
• Rheumatoid arthritis: Here, the joints in the hands and feet are particularly affected.
• Celiac disease: Affected individuals have a lifelong intolerance to the gluten protein.
• Multiple sclerosis: This is a chronic inflammation of the nervous system.
• Crohn’s disease: This is a chronic inflammatory bowel disease.

Outlook: What can be derived from the study results

The authors of the study point out that further studies need to be conducted to investigate the association of autoimmune diseases. Because the present study could only prove that there is such a connection between endometriosis and some autoimmune diseases. However, this does not mean that there is not also a connection between endometriosis and other autoimmune diseases. In addition, the question needs to be clarified whether endometriosis is a trigger or of autoimmune diseases, whether endometriosis is a consequence of autoimmune diseases or whether both diseases have similar underlying causes, i.e. have similar or identical triggers.

Another recent study [7], mentioned above, which investigated the connection between endometriosis and the autoimmune disease rheumatoid arthritis (RA), seems to answer at least one question: Since in this study women with endometriosis were observed over a longer period of time who did not (yet) have RA at the beginning of the study, endometriosis in any case does not seem to be the consequence of RA. It seems more likely that the autoimmune disease follows endometriosis or that both diseases have a similar cause.

The authors of the study call on treating physicians to consider the other disease in the case of corresponding symptoms and a diagnosed autoimmune disease or endometriosis.

Summary:

Although endometriosis affects up to 15 percent of the female population of reproductive age, too little is known about the cause of the disease to date. Recent studies have provided evidence that endometriosis is a systemic disease. A recent study has now investigated the relationship between endometriosis and autoimmune diseases. Here, a connection with endometriosis could be demonstrated for at least six autoimmune diseases. Further studies must now show in what way the two diseases influence each other, cause each other or are due to the same causes.