What Causes Mast Cell Activation Syndrome?

For some people, mast cells are more prone to release the mediator contents. However, for many, there is an underlying cause (or causes) that increases the risk of developing mast cell activation syndrome. Common causes of mast cell activation syndrome are:

• Bacterial infections
• Viral infections
• Fungal infections
• Heavy metals
• Herbicides
• Mold illness
• Allergens – food and environmental
• Genetically predisposed

Common Triggers of Mast Cell Activation Are:

• Heat
• Stress
• Exercise
• Physical trauma
• Alcohol
• Foods
• Hormonal changes
• Medications
• Odors
• Insect stings

Mast Cells Release Chemical Mediators

Inside of each mast cell, there are tiny sacs called granules. Granules contain up to a couple of hundred chemical mediators that get released when a trigger such as an allergen or toxin binds to a mast cell. Histamine is the most common mediator released from mast cells in response to an allergen such as pollen. Other mediators include tryptase, heparin, prostaglandins, leukotrienes, and cytokines. Different mediators can cause a unique physiological reaction to surrounding tissue. For example, tryptase is a proteolytic enzyme and can break down nerve endings.

Who Is At Risk for Mast Cell Activation Syndrome?

Since mast cells are present in all humans, there is the potential for anyone can develop mast cell activation syndrome. People who have developed immune dysfunction from chronic infections, toxin exposure, repeated allergen exposure, and individuals with genetic variations are at an increased risk of developing MCAS.

One study reported on over 400 patients with MCAS and identified the prevalence of specific characteristics. Women made up 69% of patients with mast cell activation syndrome, and 75% were Caucasian. The most frequent age at onset of symptoms was nine years old, and in most patients, it took 30 years to get a diagnosis of MCAS. This implies people with MCAS may spend a good portion of their life without a proper diagnosis. Other surveys have confirmed females have an increased incidence of MCAS.

Symptoms of Mast Cell Activation Syndrome

After receiving a diagnosis of mast cell activation syndrome in adulthood, many people realize the symptoms they have experienced since childhood were related to  MCAS. It is common for children (and their parents) to be told by their pediatrician they will “outgrow” their symptoms. Because mast cells are located throughout the body and contain over a hundred inflammatory compounds, symptoms can occur in every organ system. This multi-symptom, multi-system involvement, and because mast cell activation syndrome is not well-recognized, creates an extreme challenge for physicians to diagnose.

The most common symptoms of mast cell activation syndrome are:

• Systemic – fatigue, sensitivity to food and medication
• Respiratory – nasal congestion, shortness of breath, throat swelling
• Neurological – headaches, migraines
• Mental/emotional – decreased concentration, memory; anxiety, depression
• Musculoskeletal – aches, bone pain, osteoporosis
• Digestive – nausea, vomiting, heartburn (GERD), diarrhea, abdominal cramps
• Skin – flushing, itching, hives, temperature dysregulation
• Cardiovascular –high and low blood pressure, lightheadedness, racing heart, hypercoagulation
• Respiratory – shortness of breath, asthma
• Genitourinary – irritable bladder, interstitial cystitis

Lyme Disease is Associated with Mast Cell Activation Syndrome (MCAS)

Pathogens such as viruses, bacteria, fungi, and parasites can contribute to mast cell activation syndrome. The mast cell reaction is an immune response in an attempt to protect the human from the pathogen.

When Lyme disease – or other infections – and mast cell activation syndrome are present, MCAS is part of the immune dysregulation and contributing to symptoms. A research study confirmed the bacteria that causes Lyme disease triggers mast cell degranulation.

Mold Exposure can Cause Mast Cell Activation

Human exposure to environmental molds and their toxins (mycotoxins) causes immune dysfunction and immune suppression.  Mold and mycotoxins are also involved in mast cell activation syndrome. Suppose someone is experiencing any MCAS symptoms and has been exposed to a water-damaged building or environmental mold. In that case, it is critical to test for mold illness properly. Addressing mold toxicity helps to improve the outcome of mast cell activation syndrome.

Mast Cell Activation Syndrome Diagnosis

The clinical symptoms of mast cell activation syndrome should clue the physician in to order laboratory tests to confirm this suspicion. Multiple diagnostic criteria for mast cell activation syndrome have been proposed by mast cell researchers, physicians, and organizations.

The greatest challenge in diagnosing MCAS with laboratory testing is the proper handling of blood and urine samples. The samples require constant chilling to maintain stability. A 24-hour urine sample is collected at home before the blood draw. It is kept in the refrigerator and transported in a cooler to the lab. The laboratory phlebotomist also needs to be aware of keeping the samples chilled at the time of the blood draw. Proton pump inhibitors (Prevacid, Prilosec, etc.) and NSAIDs (Advil, Tylenol, etc.) need to be avoided five days before testing.

Even if the specimens are handled properly, it can be challenging to see even one mediator elevated due to the timing of mast cell degranulation. One approach is to collect the samples during a flare of MCAS symptoms.

The diagnostic workup for MCAS includes: 

• Tryptase, serum (chilled)
• Chromogranin A, serum (chilled)
• Prostaglandin D, plasma (chilled)
• Histamine, plasma (chilled)
• Leukotriene E4, random and 24-hour urine (chilled)
• N-methylhistamine, random and 24-hour urine (chilled)
• Prostaglandin DR, random and 24-hour urine (chilled)

Is It Mast Cell Activation Syndrome?

Mast cells are located throughout our bodies and are an essential part of our immune system. There has been an increased awareness and – likely incidence – of mast cell activation syndrome in the past decade. If you have symptoms consistent with MCAS, it is necessary to get properly tested for the above mediators. There may be underlying causes of mast cell activation syndrome for many people, including toxins, mold exposure, infections, and other environmental exposures. It is important to identify the potential causes with proper testing to improve symptoms and improve the outcome of treating mast cell activation syndrome.