Recently, one of our community members asked if there’s a link between rheumatoid arthritis (RA) and deep infiltrative endometriosis. We did some research and have summarized what we found below.
What is endometriosis?
Endometriosis is a condition that occurs in women mainly during childbearing years in which the lining of the uterus grows outside the uterus. This tissue can grow on the ovaries, fallopian tubes, intestines, bladder, or rarely, other areas. Some women have no symptoms, but common symptoms include abdominal or low back pain, infertility, heavy periods, bleeding between periods, and painful menstrual cramps. It is often chronic and may last for several years or throughout a woman’s life. While there is no cure for endometriosis, treatment can help and may include surgery, hormone treatments, and pain medications.1
Endometriosis may be categorized as mild, moderate, or severe. Deep infiltrative endometriosis (or deep infiltrating endometriosis) is a rare form of the condition in which endometriosis is found deep within the tissue of nearby organs, such as the bladder or bowel.2
Similarities in biological processes
Both RA and endometriosis are characterized by chronic inflammation. Inflammation is a normal response of the immune system to trauma or foreign invaders like bacteria. However, in autoimmune diseases, the body’s immune system is switched to react to itself, creating chronic inflammation that can damage tissues. While endometriosis has not been classified as an autoimmune disease, some researchers make a case that it acts like one.3
One of the substances that acts as a chemical messenger to increase inflammation in the tissues is interleukin (IL)-17A. IL-17A has been found to be elevated in people with RA, and recent research has also found an increase in IL-17A among women with endometriosis. While IL-17A is involved in just one of the pathways to increased inflammation, its involvement in both conditions may provide clues to a link between the disease processes of RA and endometriosis.4
Higher incidence rates of autoimmune diseases among women with endometriosis
Several studies have looked at the rates of comorbidities – separate conditions that occur in a person at the same time – in women with endometriosis. Some population studies have failed to find a marked increased incidence of RA among women with endometriosis. 5 Others have found slight increases.6-8
One study that was conducted in Taiwan found that women with endometriosis may be at a higher risk for several other chronic diseases, including diabetes, heart disease, chronic liver disease, and rheumatoid arthritis, as well as having a higher risk of developing ovarian and uterine cancers. However, the study authors admitted some of the data used to determine a higher incidence of these conditions in the population may be of low quality.6
Another study conducted in the U.S. involved surveying 3,680 members of the Endometriosis Association. Compared to the general population, women with endometriosis were found to have higher rates of hypothyroidism (9.6% vs. 1.5%), fibromyalgia (5.9% vs. 3.4%), chronic fatigue syndrome (4.6% vs. 0.03%), rheumatoid arthritis (1.8% vs. 1.2%), systemic lupus erythematosus (0.8% vs. 0.04%), Sjögren’s syndrome (0.6% vs. 0.03%), and multiple sclerosis (0.5% vs. 0.07%). Two conditions that were not found in higher rates among the women with endometriosis were diabetes and hyperthyroidism. Although this study found the rates of RA were higher in women with endometriosis compared to the general population, the rate increase was slight.7
A third study that looked at the incidence of endometriosis, systemic lupus erythematosus, and RA used data from the Nurses’ Health Study, in which 114,453 women nurses were followed over a 22-year period. All three of the conditions that were the focus of the study are characterized by dysfunction in the immune system. Of the study participants, 390 were diagnosed with RA and 103 were diagnosed with lupus. Endometriosis was significantly associated with both conditions. Among those with RA, there was a 40% more risk to develop endometriosis, compared to women in the study who did not have RA. (Those with lupus were twice as likely to develop endometriosis compared to those without the condition.) The study authors note that while there is an association between the conditions, it is not yet known how endometriosis is related to RA or lupus.8
Is there a genetic link between endometriosis and RA?
A person’s risk of developing RA is higher if they have family members who have the disease. Similarly, endometriosis also tends to run in families, with a person’s risk of developing the condition being higher if their family members have endometriosis. This familial frequency indicates some of the risk of a disease is passed down through the genes.
While the exact causes of endometriosis and RA are still unknown, researchers have uncovered some genetic clues for each of the conditions. Despite the similarities in inflammation and the higher incidence of RA and endometriosis, to date, there hasn’t been a genetic mutation that is common for both conditions.3
Note: The question we got was specifically about deep infiltrative endometriosis, which is a rare form of endometriosis. The journal articles and research we found focused on endometriosis as a whole, with a small percentage of the people having deep infiltrative endometriosis.
MedlinePlus, U.S. National Library of Medicine. Accessed online on 8/22/17 at https://medlineplus.gov/endometriosis.html.
Brigham and Women’s Hospital. Accessed online on 8/22/17 at http://www.brighamandwomens.org/Departments_and_Services/obgyn/Services/infertility-reproductive-surgery/endometriosis/infiltrative.aspx.
Sundqvist J, Falconer H, Seddighzadeh M, et al. Endometriosis and autoimmune disease: association of susceptibility to moderate/severe endometriosis with CCL21 and HLA-DRB1. Fertility and Sterility. Jan 2011;95(1):437-440. doi: http://dx.doi.org/10.1016/j.fertnstert.2010.07.1060.
Ahn SH, Edwards AK, Singh SS, Young SL, Lessey BA, Tayade C. IL-17A contributes to the pathogenesis of endometriosis by triggering pro-inflammatory cytokines and angiogenic growth factors. Journal of immunology (Baltimore, Md : 1950). 2015;195(6):2591-2600. doi:10.4049/jimmunol.1501138.
Nielsen NM, Jorgensen KT, Pedersen BV, Rostgaard K, Frisch M. The co-occurrence of endometriosis with multiple sclerosis, systemic lupus erythematosus and Sjogren syndrome. Hum Reprod. 2011 Jun;26(6):1555-9. doi: 10.1093/humrep/der105.
Teng S-W, Horng H-C, Ho C-H, et al. Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan. Journal of the Chinese Medical Association. 2016;79:577-582. doi: tp://dx.doi.org/10.1016/j.jcma.2016.04.006.
Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002 Oct;17(10):2715-24.
Harris HR, Costenbader KH, Mu F, et al. Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses' Health Study II. Ann Rheum Dis. 2016 Jul;75(7):1279-1284. doi: 10.1136/annrheumdis-2015-207704.