Mast Cell Disorders

Mast cells are types of white blood cells that generally are found in the connective tissue. They are a central part of our immune system as they aid in fighting off infections and other foreign intruders as well as wound healing. Mast cells look similar to basophils, which are other type of white blood cells, that contain granules. In these granules, there are a multitude of chemical substances that have effects on the body such as allergy symptoms and inflammation. The most common chemical mediators found in mast cells include histamine, tryptase, heparin, leukotrienes, prostaglandins, cytokines, and serotonin. Histamine is one of the chemicals that is responsible for the typical itchiness, swelling, runny nose, nasal congestion, chest tightness, nausea, vomiting, diarrhea, wheezing, and/or shortness of breath found in individuals who have had allergic reactions. Histamine causes inflammation, increased mucus production, decreased blood pressure, increased heart rate, and increased smooth muscle contraction in the lungs, uterus, and stomach, among other functions.

The 3 major types of mast cell disorders are identified as follows:

• Mast cell activation syndrome (MCAS) – Caused by the abnormal release of mast cell mediators which can affect any organ system, particularly the skin. The gastrointestinal tract, nervous system, and cardiovascular system is commonly involved. Can also be caused by the increased number of genetically altered mast cells.
• Cutaneous mastocytosis – Caused by an increased number of mast cells. Only affects the skin and more common in children. Defined by red or brown itchy lesions on the skin. The most common type is called urticaria pigmentosa.
• Systemic mastocytosis – Caused by an increased number of mast cells. Affects other parts of the body besides the skin such as bone marrow, lymph nodes, intestines, stomach, liver, and spleen. Very rarely, mast cell leukemia or mast cell sarcoma can occur in patients with systemic mastocytosis.

Symptoms:

As mentioned previously, children are more likely to have symptoms limited to the skin whereas the majority of adults have systemic symptoms which usually involve multiple organ systems.  The organ systems often affected may include: skin, respiratory, cardiovascular, neurologic, gastrointestinal, lymphatic, and bone marrow. The symptoms of mast cell disorders, as mentioned before, are similar to that of anaphylaxis. The symptoms of mast cell disease may include:

• Skin: Red or brown, itchy lesions over various parts of the body. If the lesions are rubbed, they become redder, swollen, and may result in blisters which is called Darier’s sign. Some patients also develop dermatographism, which is a condition which in Latin means “write on skin.” In this condition, one is able to write on the skin with a blunt object. Urticaria pigmentosa is more prevalent in children and usually improves with age. Frequent episodes of flushing (especially on the face), hives (i.e., urticaria), and/or generalized itching (i.e., pruritus) are also other common skin manifestations.
• Gastrointestinal: Nausea, vomiting, abdominal pain, abdominal bloating, discomfort after eating, pale stools
• Respiratory: Wheezing, coughing, chest tightness, shortness of breath
• Cardiovascular: Decreased blood pressure, lightheadedness, fainting (i.e., syncope)
• Neurologic: Headache, numbness, tremors
• Bone marrow: Bone pain, fractures, anemia
• Lymphatic: Swelling of lymph nodes, liver, spleen and other organs

Triggers:

Individuals with mast cell disease are more sensitive to various triggers such as temperature changes, surgery, friction, spicy foods, food preservatives, cheese, alcohol, bee stings, emotional stress, fever, fatigue, sunlight, physical exertion, infections (e.g., bacteria, viruses, fungi), drugs (e.g., aspirin, opioids, antibiotics), strong odors, perfumes, and/or chemical irritants.  Occasionally individuals with mast cell disorders will suffer anaphylaxis spontaneously without exposure to any obvious trigger(s).

Diagnosis:

The first stage in the diagnosis of mast cell disorders is a comprehensive history taking note of the specific symptoms, as well as their onset, progression, and severity.  Physical examination may disclose freckle-like brown or reddish skin lesions called “urticaria pigmentosa” which typically appear over one’s thighs, abdomen, etc. These spot-like skin lesions can lead to hives upon stroking the skin (also known as Darier’s sign), as well as after exposure to temperature changes (e.g., taking hot showers).  This phenomenon occurs as a result of the compression of mast cells.

The most useful diagnostic laboratory test is a serum tryptase level, which is usually elevated in individuals with systemic mastocytosis.  A urinalysis also can be helpful in sensing higher levels of metabolites of various chemical mediators of allergic reactions.  Confirmation of the diagnosis usually requires a skin biopsy, bone marrow biopsy, evaluation of organ functions, and occasionally genetic studies. Chest and bone X-rays and bone scans are sometimes needed. Allergy skin prick testing may be performed to foods and/or environmental allergens if flare-ups on exposure is suggested by the history from the patient.

Treatment:

Unfortunately, there is no cure for mast cell disorders, however, many signs and symptoms can be treated in order to help reduce symptoms as well as help preserve the function of organs systems.

The usual course of treatment is avoiding exposure to the known triggers of mast cell activation in order to prevent acute symptoms. There are a variety of medications that are used in to treat mast cell disorders.

Itching, flushing, and other skin allergy symptoms can be controlled by usingH1-blocking antihistamines. These antihistamines block the effects of histamine, a common mediator in allergic reactions. Histamine is stored in mast cells and released during activation of the mast cells. As a result, antihistamines [e.g., Claritin (loratadine), Allegra (fexofenadine), Zyrtec (cetirizine)] are the most commonly used medications to treat mast cell disorders. Occasionally, H2-blockers (e.g., Tagamet (cimetidine), Pepcid (famotidine) are used in conjunction with H1-blocking antihistamines for more recalcitrant cases.

Medications that stabilize mast cells so they do not degranulate and release their chemical mediators such as cromolyn, nedocromil, or ketotifen are helpful in alleviating the gastrointestinal symptoms (i.e., nausea, vomiting, abdominal cramping) that may occur with mast cell disorders.
Anti-inflammatory medications such as oral corticosteroids (e.g., prednisone), aspirin, and leukotriene modifiers [e.g., Singulair (montelukast), Accolate (zafirlukast), Zyflo (zileuton)] are sometimes utilized in the treatment of systemic symptoms of mast cell disease. Topical corticosteroid creams or ointments, as well as phototherapy can improve localized skin lesions.

Individuals with respiratory symptoms (i.e., coughing, wheezing, chest tightness, shortness of breath) may benefit from using asthma-type inhalers such as albuterol (e.g., ProAir, Proventil, Ventolin)

Digestive symptoms caused by mast cell conditions may be improved with proton pump inhibitor (PPI) medications [e.g., Prilosec (omeprazole), Prevacid (lansoprazole), and Nexium (esomeprazole)]. Anticholinergic medications may be used to reduce the motility of the bowels which may help control diarrhea.

Immune modulating medications (e.g., interferons), chemotherapeutic agents, bone marrow transplant, and/or stem cell therapy may be used in more severe cases of systemic mastocytosis.

Surgical removal of the spleen can also help improve severe symptoms in some individuals.

It should be noted that individuals with mast cell disorders should pay special attention to bone health as they are at risk for fractures due to osteopenia and/or osteoporosis.

It is also important for patients with mast cell disorders to make surgeons and anesthesiologists aware of their mast cell disorder in case a surgical procedure is needed, as surgery can be a trigger of systemic symptoms.

All patients with established mast cell disorders should carry a self-injectable epinephrine device (e.g., EpiPen, Auvi-Q, Adrenaclick) at all times to be used at the onset of symptoms indicative of anaphylaxis.  It is important for the individual to go to the closest emergency room after using such a device.

Prognosis:

Children and individuals who only have skin involvement tend to have little or no progression of their disease over time. Most cases of localized mast cell disease can persist for many years as nodules on the skin. Older individuals and those with widespread systemic disease involving other organ systems however, have a poorer prognosis. Systemic mastocytosis tends to be persistent at a low level for decades, requiring treatment to control symptoms. Occasionally, however, it can become aggressive and even life-threatening. In rare instances of systemic mastocytosis, mast cell cancers can develop, so constant monitoring is important in these individuals.

The board certified allergists at Black & Kletz Allergy have 3 convenient office locations in the Washington, DC, Northern Virginia, and Maryland metropolitan area and are very experienced in the diagnosis and treatment of mast cell disorders. Black & Kletz Allergy treat both adults and children and have offices in Washington, DC, McLean, VA (Tysons Corner, VA), and Manassas, VA. We offer on-site parking at each location and the Washington, DC and McLean, VA offices are Metro accessible. There is a free shuttle that runs between the McLean, VA office and the Spring Hill metro station on the silver line. Please call our office to make an appointment or alternatively, you can click Request an Appointment and we will respond within 24 hours by the next business day. Black & Kletz Allergy has been serving the Washington, DC metropolitan area for more than a half a century and we pride ourselves in providing first-rate allergy, asthma, and immunology care in a professional and pleasant setting.