Mast cells are important cells in our immune systems that help us fight off sickness, infections, and allergies. Although these cells are vital to protecting our bodies, some peoples’ mast cells can be too active for no good reason. In these cases, the mast cells might cause more harm than good. When Mast Cells are overly active, Mast Cell Activation Syndrome (MCAS) may sometimes be diagnosed. In MCAS, Mast Cells release excessive chemicals into the bloodstream. This reaction can cause swelling, hives, coughing, and pain.

There are three main types of MCAS that are recognized:

1. Primary
2. Secondary
3. Idiopathic.

Primary MCAS is when the bodies’ mast cells clone themselves excessively. In these cases, mast cells gather in organ tissues in excessive numbers. Symptoms of primary MCAS can occur in pretty much any organ in the body. Common symptoms are allergy-like. For example, skin rashes, hives, and abdominal pain. Especially serious cases of primary MCAS can be called mastocytosis, a life-threatening condition that can cause serious allergic reactions called anaphylaxis.

Even though you may have not heard of it, you are probably familiar with secondary MCAS. Do you have any allergies? If so, you may have secondary MCAS. Secondary MCAS may be diagnosed when a person experiences allergic reactions, for example, to nuts or shellfish. Unlike in primary MCAS, mast cells do not clone themselves abnormally in second MCAS. In fact, people with secondary MCAS have a perfectly normal amount of mast cells. However, these mast cells are overactive and release excessive chemicals into the bloodstream (such as histamine), which cause allergic like reactions. Some examples of environmental triggers can include pollen, food, and alcohol.

Idiopathic MCAS is an interesting condition that can be frustrating for patients who have it. This is because these patients experience allergy-like symptoms, but they are not allergic to anything. In other words, idiopathic MCAS can cause seemingly allergic reactions for no reason at all. For MCAS to fall into the idiopathic category, there must be no evidence of an excessive amount of mast cells (primary MCAS), and the allergy-like symptoms must not be triggered by an actual allergy. For someone to be diagnosed with idiopathic MCAS, the doctor must make sure that they rule out all potential causes of the allergy symptoms.  Although not typically, patients with idiopathic MCAS may still have serious reactions (anaphylaxis).MCAS in all its forms is treatable through different strategies. Helpful interventions for primary, secondary and idiopathic MCAS may include antihistamines to calm allergy symptoms. For cases of secondary MCAS where the allergic trigger is known, lifestyle changes can go a long way in calming down mast cells.

Are your “allergic symptoms” and pain related to idiopathic Mast Cell Activation Syndrome (MCAS)?

Hives, rashes, itching, problems breathing, and pain in your stomach or other parts of your body may all be related to allergies. Your doctor may have tested you, but did not find what you might be specifically allergic to, for example types of foods or substances surrounding us like pollen, dust, and mold. If you didn’t have evidence of an allergy to any or only a few of these substances, then what is causing your symptoms?

Your symptoms may be caused by excessive activity in a special cell in your body called the Mast Cell (MC) which is stimulated whenever you experience any irritation. The MC helps to fight off infections and help repair damaged tissue by producing many different powerful substances. However, when it is overactive, these substances may be produced by the MC after exposure to ordinary stimuli including a hot shower, sunlight, perfumes, cleaning solutions, and a variety of foods. Overactive MCs may cause diffuse pain in various parts of your body.

Doctors have been aware that increased numbers of MCs can cause serious symptoms in different organs. When there are too many MCs the diagnosis is often Mastocytosis, which requires specialized treatment. When the number of MCs is normal and the MCs are just overactive, the diagnosis, which is a relatively new discovery, is often idiopathic Mast Cell Activation Syndrome (MCAS) and can be diagnosed with several blood and urine tests. However, if you have symptoms in 2 or more organ systems, for example skin rashes, heart burn, asthma like symptoms, and your symptoms improve with an anti-histamine, you may be diagnosed with idiopathic MCAS without complicated testing.

Our body makes a substance that can down-regulate the activity of the MC. It is called palmitoylethanolamide (PEA). It is in the family of substances, called cannabinoids, and is related to the molecules that are present in marijuana. Other substances can down regulate the MC such as Cromolyn Sodium. Since one of the main substances produced by the MC is histamine, medications that block histamine. such as antihistamines used for allergies and histamine antagonists used for heart burn, may be helpful in reducing the symptoms of overactive MCs.

If you have diffuse pain and other symptoms, like the ones above, that have been difficult to diagnose and treat, you may have MC problems that can be treated.

How do we test new medicines before they are released to the public?

Let’s say for the sake of this example that there’s a new drug that is potentially effective at treating people with muscle pain. The process to test that treatment is called clinical trials. To test the medicine, clinical trials occur in different stages, called phases. Phase I testing is done on healthy volunteers without muscle pain. If the drug is found have unsafe side effects, it would fail phase 1 and be withdrawn from further testing. If the drug passes Phase 1, it goes on to Phase 2 which studies a small group of patients with muscle pain to see if the new drug is effective in treating the condition without producing serious side effects. If the drug passes Phase 2 it goes on to Phase 3 which tests a larger group of patients with muscle pain to confirm the effectiveness and safety found in Phase 2.

There are strict guidelines that researchers must follow when conducting clinical trials to ensure the safety of their human subjects. Regulatory bodies such as the FDA monitor clinical trials to ensure that all guidelines are being followed. If the physicians in charge of a new drug trial are found to not follow the guidelines, they are removed from their trial and may lose their ability to participate in any future trials.

Participation in a new drug study can be an exciting experience–especially when it results in a decrease or elimination of your symptoms. Before a patient begins a clinical trial, all the possible risks that may occur during the study are spelled out in a document called the consent form. The consent form is signed by the participant before they start treatment. The consent form makes it clear that declining to participate in a study will not affect the participant’s future care, and that they may withdraw from the study at any time for any reason.

A drug study is an experiment. To ensure that enthusiasm about the new drug doesn’t influence the outcome–for example hoping that the treatment is going to work will make you believe that it works–some participants will receive an inactive drug called a placebo. Whenever possible, the physician administering the drug will not know if they are giving you the real drug or the placebo. This type of study, where the physician and the study participant do not know which medication they receive, is called a double-blind study. Participants are informed at the end of the study if they received the active drug or the placebo.

Some drug trials provide financial compensation for time and participation. Some trials will only compensate you for any expenses that you incur in the process of participating in the study. Participation in a study may or may not benefit you directly but will potentially benefit many patients in need of new effective treatments.

A recent study done in Turkey took a look at the walking patterns of chronic pain patients- ideopathic neck pain, to be specific. They based their hypothesis around previous studies that have shown that people with chronic ideopathic neck pain (CINP) had abnormal walking patterns (known as gait), whether it be in the physical pattern or in the timing of their walks.

The scientists recruited 20 individuals with CINP as well as 20 healthy individuals without CINP to perform 10 minute walking tests with pressure sensitive insoles inserted into their shoes. They performed three different tests: Preferred walking, preferred walking with head rotation, and walking at maximum speed.

The study showed that individuals with CINP had a slower gait speed in all three walking conditions compared to the control groups. The gait was also found to be asymmetric in individuals with CINP in two out of three of the different test groups. This is important because gait asymmetry has the potential to load your entire body unequally, causing unbalanced strain on your muscles, joints, and other problem areas. These can lead to other musculoskeletal problems in the future.

Here at Norman Marcus Pain Institute, we see many patients with chronic pain everywhere, not just in the neck. We also often see collapsed arches in patients’ feet as well as uneven strides that can be magnifying discomfort on one side of the body vs the other. Recently we have started recommending special orthotics designed to strengthen and correct imbalances and weak arches. We occasionally recommend that our patients see a professional gait analyst to find ways to correct these imbalances to relieve some of the strain that their muscles may be experiencing.

In May 2017, there were several changes in the criteria for the diagnosis of what used to be Ehlers-Danlos Syndrome Type III, hypermobility type. First, the name has been changed to hypermobile Ehler-Danlos Syndrome or hEDS. Instead of six types, there are now 13 types.

hEDS continues to have no obvious known genetic testing and is only diagnosed through clinical testing.

As mentioned earlier, the Beighton scale is used to determine if a person is hypermobile. This continues to be an important determinant for hypermobility. A 5/9 score in adults is needed in order to meet this requisite. However, because age has an effect on flexibility (ie with age, you tend to become stiffer), there is a Five Point Questionnaire that determines if there is a history of hypermobility. The five points are the following:

• Can you now (or could you ever) place your hands flat on the floor without bending your knees?
• Can you now (or could you ever) bend your thumb to touch your forearm?
• As a child, did you amuse your friends by contorting your body into strange shapes or could you do a split?
• As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?
• Did you consider yourself “double-jointed”?

If you answer yes to two or more questions, then you have met the criteria for hypermobility (with 80-85% sensitivity and 80-90% specificity).

The Beighton Scale and Five Point Questionnaire are the first part of three criteria that need to be met in order to qualify for the diagnosis of hEDS. This criterion also meets the diagnosis of hypermobility (you can have generalized joint hypermobility without a diagnosis of hEDS).

The second criterion has three parts (A, B, and C), of which two must be met to qualify. Part A is a series of 12 symptoms, of which five must be met in order to quality:

• Unusually velvety skin
• Mild skin hyperextensibility
• Unexplained striae on back, groins, thighs, breast or abdomen in adolescents, men or prepubeteral women without a history of significant gain/loss or weight.
• Bilateral piezogenic papules of the heel
• Recurrent or multiple abdominal hernias (umbilical, inguinal, crural)
• Atrophic scarring with papyraceous or meosideric scars
• Pelvic floor, rectal and/or uterine prolapse in children, men or nulliparous women without a history of morbid obesity or other known predisposing medical conditions.
• Dental crowding or high or narrow palate
• Arachnodactyly (fingers & toes, long and slender), Steinberg Sign (thumb beyond palm), Walker-Murdoch sign (thumb overlapping fifth finger around wrist)
• Arm span to height ≥ 1.05
• MVP
• Aortic root dilation

Part B is a positive family history of one or more first degree relatives, independently meeting the criteria of hEDS.

Part C is musculoskeletal complaints; a patient must have at least one to qualify:

• Daily musculoskeletal pain at least three months in two or more limbs
• Chronic widespread pain for more than 3 months.
• Recurrent joint dislocation or frank instability in the absence of trauma (A or B)
  • 3 or more atraumatic joint dislocations in the same joint or two or more atraumatic dislocations in two different joints occurring at two different times.
  • Medical confirmation of joint (2 or more) instability

The third criterion contains three pre-requisites, all of which must be met:

1. Absence of unusual skin fragility which should prompt consideration of other types of EDS.
2. Exclusion of other heritable and acquired connective tissue disorder with autoimmune connective tissue disorder (ie Lupus, RA).
3. Exclusion of alternative diagnoses that may also include joint hypermobility by means of hypotonia and/or CT laxity. Alternative diagnoses and diagnostic categories include, but not limited to, neuromuscular diseases, myopathic EDS, Bethlem myopathy, or HCTD (ie other types of EDS), Loeys-Dietz Syndrome (Marfan), and skeletal dysplasias (ie OI).

References

American Journal of Medical Genetics, Part C. (Seminars in Medical Genetics), March 2017.