Ehlers Danlos and Mast Cell Activation

Mast cells (MCs) are immune system cells that inform the body when something isn’t supposed to be there. MCs can cause problems when the immune system isn’t working correctly. Allergies, nerve problems, and connective tissue disorders may all be caused by MCs. This report aims to provide an overview of mast cell biology and recent research into how mast cells may be involved in diseases such as Ehlers-Danlos Syndromes (EDS).

Introduction: Mast Cells and Their Properties

Mast Cells (MCs) were first discovered by German physician and scientist Paul Erlich in the late 1800s. Around blood vessels and connective tissue, he noticed a new form of cell with large granules within. Erlich mistook these cells for feeding others and dubbed them “Mastzellen” (German for “fattening cells”). Mast cells are part of the immune system, protecting the body from parasites and other foreign invaders.

MCs start as blood stem cells in the bone marrow and shift depending on where they end up in the body. Unlike other immune cells, mature (entirely changed) MCs are expected to remain in the tissue they have transferred to (such as nerves and blood vessels). Mast cells are stimulated when the body interprets anything as potentially harmful. The mast cells then produce histamine release into the surrounding tissue to signal the body to react, resulting in swelling, warmth, and redness (inflammation). While MCs are best known for their function in allergic reactions such as asthma, food allergies, and anaphylaxis, new research indicates they may also play a role in various non-allergic disorders.

Mast Cell Activation Disorder

The Extracellular Matrix (ECM) is a network that surrounds and supports body cells and comprises structural materials, including collagen. Collagen and other structural materials play an essential role in the body’s connective tissue and are linked to Ehlers-Danlos syndromes (EDS). The ECM will help MCs stay on track, which changes their actions. As a connective tissue disorder, EDS may alter the ECM sufficiently to alter MC behavior.

Mast cell activation disorder (MCAD) is a disease in which mast cells (MCs) activity is abnormally high. Since many people with hypermobile EDS (hEDS) also have MCAD, there could be a correlation between the two conditions; research appears to back this up. According to one report, sixty-six percent of patients with both a high heart rate while standing (Postural Tachycardia Syndrome or POTS) and EDS had symptoms associated with MC activation.

MCAD’s features

Patients with MCAD may have a wide range of symptoms, which is likely due to genetic variations. Itching, redness, skin injury, and diarrhea, and abdominal pain are all possible symptoms. Alcohol, heat, medications, invasive procedures (surgery, biopsy, endoscopy), insect stings, high body temperature (fever) or infection, exercise, physical contact (pressure, friction), emotions/stress are some of the most common MCAD causes.

Although some of these tests are not good enough for proper diagnosis, are generally not available to a family doctor, or are costly, laboratory tests should analyze blood and urine samples for chemicals unique to MCs. A doctor can test any or more of the following molecules: serum tryptase and chromogranin A, plasma histamine, prostaglandin (PG)D2, and heparin, as well as urinary histamine, N-methylhistamine (NMH), PGD2, 11-b-PGF2a, and leukotriene (LT) E4 (random and 24-hour). It could be beneficial to take a small sample of the gut to monitor for MCs. Since some of the molecules studied do not remain in the body for long periods of time or may break down outside the body, it is essential to keep this in mind when collecting and storing these samples. When a patient has more apparent signs, negative tests in those with possibly MCAD will need to be repeated.

MCAD Treatment.

It is unknown whether having EDS and MCAD combined affects the treatment process. Except for a rare subtype called solid mastocytoma, MCAD is currently incurable, and treatment is restricted to symptom management. For the efficient management of most complex diseases, like MCAD, an influential doctor is crucial. The lack of a local “doctor/partner” who can reliably assist the patient in accessing local and remote health care services can make it difficult for the MCAD patient to obtain and maintain control of their disease.

It’s essential to figure out what causes symptoms and stop them (foods, chemicals, medication, or other causes). It’s important to remember that non-drug ingredients in pills can cause an allergic reaction in MCAD patients. If a reaction occurs after the first few doses of a new drug, the components should be examined to determine the cause, and then alternatives should be sought. Patients with MCAD can need drug formulations that are unique to them. Some patients respond to various foods; eliminating ingredients from the diet and reintroducing them one at a time (an elimination diet) can benefit some of these patients, but not all. It’s crucial to keep as many other things the same as possible: switching medications simultaneously can lead to confusion if a reaction happens again.

Despite their exhaustion and ill health, MCAD patients should be encouraged to exercise regularly. This can only be done up to the patient’s tolerance limit, which he or she has most likely experienced through experience. This is because, in some patients, overexertion will cause MC activation to flare up. Since MCs are activated by physical and psychological stress, reducing stress (e.g., psychotherapy) may be beneficial. Desensitization therapy (gradually growing sensitivity to the allergen) is a possibility.

All patients at risk of having a severe allergic reaction (anaphylaxis) should be given two self-injectable epinephrine devices and taught how to use them. Many medications have been shown to benefit MCAD patients greatly, but there are currently no methods for predicting who will react to which drug and who will not. Since each patient’s tolerance and benefit differs, drug treatment must be personalized to them individually. H1 and H2 antihistamines, sodium cromoglicate, ketotifen, omalizumab, and leukotriene receptor blockers are commonly used drugs. Vitamin C, aspirin, flavone analogs, and cannabinoids are other drugs that patients may find beneficial. Medications should typically be added one at a time, with a sufficient time interval between each addition. Some patients need a lower starting dose before eventually increasing to an average amount. Patients should be informed that side effects can take several weeks to manifest.

Decongestants, bronchodilators, antiemetics, proton pump inhibitors, antidepressants of different groups (e.g., tricyclic agents), bowel motility agents, micronutrient supplements, pancreatic enzyme supplements, bone-strengthening agents, and tumor necrosis factor (TNF) alpha antagonists are among the helpful drugs used by MCAD patients.

Pain is one of the most typical symptoms of MCAD, second only to fatigue. NSAIDs such as aspirin and ibuprofen can benefit some patients, but they can also cause anaphylactic reactions in others, so they must be used cautiously. Narcotics are also common triggers; opioids, tramadol, and hydromorphone are more tolerated in MCAD patients than others. Other groups of MC-targeted agents, which usually have no analgesic effect, may sometimes be found to be analgesic (e.g., antihistamines may relieve chronic migraine headaches in some MCAS patients).

There are no extensive, high-quality studies of any MCAD intervention. Both the patient and the treating doctor must take a systematic approach to try the various treatments that might be beneficial, restricting themselves to one improvement at a time wherever possible. Most of these treatment trials are only 1–2 months long, with low doses initially and escalating step-by-step as tolerated to determine successful dosing. In the absence of a more scientifically based plan, the most rational solution is to proceed in order of care cost.

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