Endometriosis is a chronic inflammatory condition that affects an estimated 10% of women of reproductive age worldwide (1). It is characterized by the growth of endometrial-like tissue outside of the uterus, typically on the ovaries, fallopian tubes, and pelvic lining, and can cause chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility (2).
While the exact cause of endometriosis is unknown, it is believed to involve a combination of genetic, hormonal, immune, and environmental factors (3). Recent research has also suggested a potential link between endometriosis and Mast Cell Activation Syndrome (MCAS).
What is Mast Cell Activation Syndrome?
MCAS is a relatively newly described disorder characterized by the over-activation of mast cells, immune cells that play a critical role in the body’s immune response by releasing histamine and other inflammatory mediators (4). In MCAS, mast cells are triggered by a variety of stimuli, including physical, environmental, and emotional stressors, leading to the release of excessive amounts of histamine and other inflammatory substances. This can cause a wide range of symptoms, including flushing, itching, abdominal pain, diarrhea, and shortness of breath (5).
Idiopathic MCAS is a form of the condition where there is no apparent cause for the overactive mast cells. In some cases, MCAS can be triggered by an infection or other underlying medical condition, but in many cases, the cause is unknown (6).
Several studies have reported a high prevalence of mast cells in various tissues and fluids collected from women with endometriosis, with some reporting elevated levels of mast cells in up to 80% of cases (7,8). This strongly suggests a potential link between the two conditions.
One proposed mechanism for the link between MCAS and endometriosis is that mast cells play a role in the development and progression of endometriosis by promoting angiogenesis, inflammation, and nerve growth (9). Endometriotic lesions have also been shown to release a variety of factors that can activate mast cells, such as vascular endothelial growth factor (VEGF), substance P, and nerve growth factor (NGF) (10).
The symptoms of MCAS can overlap with those of endometriosis, which can make it difficult to diagnose. Women with MCAS may be misdiagnosed with other conditions such as irritable bowel syndrome (IBS) or fibromyalgia (11). Therefore, healthcare providers need to consider the possibility of MCAS in women with endometriosis who have unexplained wide-ranging inflammatory symptoms.
Treatment of MCAS
The treatment of MCAS typically involves a combination of medications and lifestyle changes. Antihistamines, which block the release of histamine from mast cells, are commonly used to reduce symptoms, along with other medications such as mast cell stabilizers and leukotriene inhibitors (12). Lifestyle changes such as stress reduction, avoiding triggers, and a low histamine diet may also be helpful in managing the condition (13).
In addition to treating the symptoms of MCAS, it is important to address the underlying causes of the condition. For example, one study found that women with endometriosis and MCAS who received a combination of hormonal therapy and MCAS treatment had significant improvements in both endometriosis-related pain and MCAS symptoms (14).
In women with endometriosis, this may involve treating the endometrial-like tissue growth and reducing inflammation in the body. Hormonal therapy, such as birth control pills or GnRH agonists, may be effective in reducing the symptoms of endometriosis and preventing the growth of endometrial tissue (15). However, the latter (GnRH agonists) is fraught with major side effects, including bone loss, if used for more that six months. GrRH antagonists may be safer to use for longer periods of time but still present quality of life side effect problems.
Does Endo Excision Surgery Help MCAS?
The role of excision surgery in women with endometriosis and Mast Cell Activation Syndrome (MCAS) is a topic of ongoing research and debate. Excision surgery is a surgical technique that involves removing endometriotic tissue lesions in a meticulous and thorough manner to reduce the recurrence rate of endometriosis. This requires surgeons who are trained in and specialize in this technique, which is usually well beyond the skill set of most general gynecologists.
While excision surgery is considered the gold standard treatment for endometriosis, some studies have suggested that it may be associated with a higher risk of triggering mast cell activation in women with MCAS. This is because the surgery itself can cause mast cell degranulation and the release of histamine and other inflammatory mediators, which can worsen MCAS symptoms (16).
On the other hand, other studies have suggested that excision surgery may be beneficial for women with both endometriosis and MCAS. One study found that women with endometriosis and MCAS who underwent excision surgery had significant improvements in pain and quality of life, with no significant increase in MCAS symptoms (17).
The decision to undergo excision surgery should be made on a case-by-case basis, taking into account the severity of the endometriosis and MCAS symptoms, as well as the risks and benefits of the procedure. Women with MCAS who are considering excision surgery for endometriosis should be closely monitored for MCAS symptoms before, during, and after the procedure, and appropriate steps should be taken to minimize the risk of mast cell degranulation, such as preoperative medications to stabilize mast cells. Again, this requires working with specially trained endometriosis surgeons.
MCAS and Your Gut: Advanced Options?
There is limited research on the use of intravenous feeding hyperalimentation in the management of Mast Cell Activation Syndrome (MCAS), but it is a consideration. The symptoms of MCAS can be diverse and affect multiple organ systems, including the gastrointestinal tract. In some cases, these symptoms can be severe and debilitating, leading to malnutrition and weight loss (18).
Intravenous feeding hyperalimentation, also known as total parenteral nutrition (TPN), is a technique used to provide nutrition to individuals who are unable to eat or absorb nutrients through the gastrointestinal tract. TPN involves delivering a mixture of nutrients, including glucose, amino acids, and lipids, directly into the bloodstream via a catheter (19).
While TPN can be an effective way to provide nutrition to individuals with severe malnutrition or digestive disorders, there is limited research on its use in the management of MCAS. One case report described the successful use of TPN in a patient with MCAS who was experiencing severe gastrointestinal symptoms and malnutrition (20). After receiving TPN for several weeks, the patient’s symptoms improved, and she was able to resume a regular diet. This may also be a preoperative preparation strategy and home-health services can provide this type of nutrition at home under the direction of your physician.
It is important to note that TPN is not without risks, and it should only be used when necessary and under close medical supervision. Potential complications of TPN include infection, liver damage, and blood sugar imbalances (21).
While there is limited research on the use of intravenous feeding hyperalimentation in the management of MCAS, it may be a useful option for individuals with severe malnutrition and gastrointestinal symptoms. However, TPN should only be used when necessary and under close medical supervision. It is not a stand-alone solution. The management of MCAS typically involves a combination of medications, lifestyle and diet changes aimed at reducing symptoms and preventing mast cell degranulation.
Summary About MCAS and Endometriosis
It is important to note that while the link between MCAS and endometriosis is still being studied, not all women with endometriosis will develop MCAS, and not all women with MCAS will have endometriosis. However, given the potential overlap of symptoms and the high prevalence of mast cells in endometrial tissue in women with endometriosis, it is important for healthcare providers to be aware of the potential connection and to consider MCAS as a possible diagnosis in women with unexplained symptoms. It is critical to work with an endometriosis specialist.
Further research is needed to fully understand the relationship between the two conditions and to develop effective treatment strategies for women with both conditions. For women with endometriosis and MCAS, an individualized approach to treatment that addresses both conditions is essential to improve symptoms and quality of life.
References:
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- Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Aug;98(3):511-9.
- Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017 Feb;139(2): 349-355.
- Afrin LB. Presentation, diagnosis, and management of mast cell activation syndrome. Mast Cells. 2018;5:57-81.
- Valent P, Akin C, Bonadonna P, Hartmann K, Broesby-Olsen S, Brockow K, et al. Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome. J Allergy Clin Immunol Pract. 2019;7(4):1125-1133.
- Kaori Koga, Kiichiro Noda, Keiichi Kato et al. Possible involvement of mast cells in endometriosis. Journal of Reproductive Immunology, Volume 59, Issue 1, 2003, Pages 45-55.
- Keiko Mekaru, Chie Higa, Kana Miyagi et al. Increased mast cells in peritoneal fluid during the early follicular phase in patients with endometriosis. The Journal of Obstetrics and Gynaecology Research, Volume 42, Issue 4, 2016, Pages 401-407.
- Grassetto A, Vicenti R, Garolla A, et al. Mast cells as key players in endometriosis. Am J Reprod Immunol. 2018;80(5):e12998.
- Varras M, Akrivis C, Hadjopoulos G, et al. Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations. J Reprod Med. 2002;47(5):355-361.
- Afrin LB. Diagnosis, presentation, and management of mast cell activation syndrome. Mast Cells. 2018;5:57-81.
- Afrin LB. Mast cell activation syndrome and histamine: diagnosis and considerations for therapy. Expert Rev Hematol. 2016 Nov;9(11):1073-1080.
- Afrin LB. Presentation, diagnosis, and management of mast cell activation syndrome. Mast Cells. 2018;5:57-81.
- Chiaro TR, Patel BG, Rusch NJ, Gupta S, Nizam A, Zhu Y, et al. A prospective cohort study to evaluate triggers of recurrent acute exacerbations of non-clonal mast cell activation syndrome (NC-MCAS) in a tertiary referral center. J Allergy Clin Immunol Pract. 2020;8(7):2265-2273.
- Bedaiwy MA, Falcone T. Endometriosis and infertility. Curr Opin Obstet Gynecol. 2014 Jun;26(3):202-8.
- Kanisicak O, Aydin H, Demir S, et al. An investigation into the effects of laparoscopic excision of endometriotic lesions on the mast cell count in women with endometriosis. J Obstet Gynaecol. 2019;39(3):342-347.
- Chiaffarino F, Ricci E, Cipriani S, et al. Laparoscopic excision of endometriosis in women with non-celiac gluten sensitivity: a pilot study. Arch Gynecol Obstet. 2019;300(2):537-544.
- Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017 Feb;139(2):349-355.
- Haney CJ, Henriet E. Overview of parenteral nutrition. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014:942-952.
- Ramirez GA, Dagna L, Calcagno A, et al. Successful total parenteral nutrition in a patient with refractory mast cell activation syndrome. Ann Allergy Asthma Immunol. 2016;117(3):340-342.
- Grippaudo C, Ballardini G, Colombo E, et al. Nutritional problems in patients affected by systemic mastocytosis. J Biol Regul Homeost Agents. 2011;25(4):595-602.