MCAS - Mast Cell Activation Syndrome
Mast cells are a type of leukocyte or white blood cell that play key roles in the inflammatory process of the immune system. Mast cells reside in throughout the body in connective tissue, particularly in the areas where internal and external environments meet. This includes high concentrations in the skin, GI tract, lungs, pleura, bladder, muscles, and the mucosa lining the various cavities of the body. When mast cells are activated, typically as part of an immune response, they release the contents of granules stored within their cytoplasm in a process called "degranulation." Through degranulation, mast cells release many kinds of chemicals locally and into the blood stream triggering a response from nearby cells and systemically as part of a larger immune response. Substances released by mast cells include histamine, heparin, leukotrienes, prostaglandins which modulate inflammatory or immune response. This is a well-regulated response and diminishes afterwards.
In Mast Cell Activation Syndrome (MCAS), mast cells become activated and degranulate without “turning off” and lose regulatory control. For people with MCAS, the manifestations are similar to allergic reactions. Many common reactions include hives, itchiness, shortness of breath, anaphylaxis if severe, post-prandial (after eating) abdominal pain, generalized pain, bloating and diarrhea.
Patients with mast cell activation syndrome often have identifiable triggers including certain foods that contain high histamine, sun exposure, physical stressors, and emotional stressors.
Many patients, however, do not have these easily identifiable triggers.
Mast Cell Activation Syndrome (MCAS) is frequently associated with postural orthostatic tachycardia syndrome (POTS) and many types of Ehlers-Danlos Syndrome (EDS). Due to the common concurrent diagnoses of these conditions, they are associated as a known common triad. The reasons for this are not fully understood, however contemporary studies in mechanobiology and tissue composition suggest that the abnormal collagen found in some EDS types promote mast cell instability and the elevated degranulation associated with MCAS.
Diagnosis of Mast Cell Activation Syndrome includes obtaining careful history, performing physical examinations, and supporting laboratory studies that include blood tests and 24-hour urine collection for mast cell metabolites and granule contents.
At the moment, Mast Cell Activation Syndrome has no known cure, however, there is effective management for many of the reactions. Typical management includes lifestyle modification (low histamine diet for example), antihistamines such as loratadine, Zyrtec and H2 blockers such as famotidine. Other forms of treatment include mast cell activation stabilizers such as cromolyn sodium, ketotifen, quercetin and leukotriene E4 blockers like montelukast. If reactions are severe, biological therapeutics such as Xolair are often very effective in managing symptoms.
hEDS - hypermobile Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome (EDS) is a group of heritable disorders that affect the connective tissues of the body. These disorders occur due to variations in over 20 genes and are often characterized by alterations in the genetic coding of proteins responsible for connective tissue structure. To date, there are 13 types of Ehlers-Danlos syndrome. Hypermobile EDS, the most common subtype, has no known means of genetic testing compared to the 12 other subtypes. Hypermobile EDS or hypermobile Ehlers-Danlos syndrome is clinical syndrome of abnormal collagen in the body.
Collagen is the most abundant protein in the body. Microscopically it is a triple wound fiber and acts as scaffolding for many organs in the body. High amounts of collagen can be found in the skin 75%, tendons 90%, ligaments 80%, fascia 90+%, cartilage 67%, in addition to many other organs in the body.
In hypermobile EDS, the normally well organized collagen fibers are found in disarray which causes increased elasticity of many organs. When viewing the bodily tissue of hEDS patients with electron microscopes, the structural abnormalities result in collagen bundles arranged in disorganized flower-like patterns. This reduces the effectiveness of the collagen acting as a semi-moveable scaffolding.
This presents within people on a macroscopic scale as the hypermobility associated with hypermobile Ehlers-Danlos Syndrome. The collagen fibrils within the fascia, tendons, ligaments, skin, etc., are able to move more freely due to their disordered structure. Therefore, in tandem, the flexibility of these tissues allows for a greater range of movement in all aspects of the body.
Clinical symptoms from hypermobility EDS include progressive joint pains, nontraumatic dislocations or subluxations (partial dislocation), joint instability, smooth soft stretchy skin, in addition to other associated problems such as cervical spine instability, fatigue, pelvic floor dysfunction.
There is no known genetic mutation for hypermobile EDS (the most common presentation) and the diagnosis relies on clinical examination. The physician will check a Beighton Score as a tool for clinical diagnosis.
Management of hypermobile EDS includes rehabilitation approaches that focus appropriate hypermobility physical therapy or occupational therapy. Non-opiate pain management is a common treatment modality. More invasive treatments include joint injections with PRP ( plasma rich platelets), stem cell therapy injections (investigational) and potential orthopedic surgeries to stabilize joints, release nerve pressure due to fascial constriction, and thereby return strength and reduce pain.
