The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 57

71. What other diseases “look like” mast cell disease?

Mast cell diseases have many symptoms that are also commonly found in other disorders. This is one of the reasons why it is difficult to diagnose correctly. The following conditions have symptoms that can look like mast cell disease.

Neuroendocrine cells are specialized cells that help to pass signals from the nervous system to nearby cells, causing those cells to release hormones. There are many types of neuroendocrine tumors. Some conditions that look like mast cell disease are caused by these tumors. Symptoms from them are caused by the response of too much hormone.

Carcinoid syndrome is the result of a rare cancerous growth called carcinoid tumor. This tumor releases too much serotonin into the body. This can cause flushing, nausea, vomiting, diarrhea, difficulty breathing, and cardiovascular abnormalities such as abnormal heart rhythm. Mast cells also release serotonin but they release much less than carcinoid tumors.

VIPoma means vasoactive intestinal peptide –oma. When a word has –oma at the end, it means that it is a tumor. A VIPoma is a tumor that starts in the pancreas. It releases a chemical called vasoactive intestinal peptide. VIPoma can cause flushing, low blood pressure, and severe diarrhea leading to dehydration. A VIPoma can also abnormalities in the composition of the blood. Many patients have low potassium, high calcium, and high blood sugar.

Pheochromocytomas start as cells in the adrenal glands. They release excessive norepinephrine and epinephrine. They can cause headaches, heart palpitations, anxiety, and blood pressure abnormalities, among other things.

Zollinger-Ellison syndrome is a condition in which tumors release too much of a hormone called gastrin into the GI tract. This causes the stomach to make too much acid, damaging the stomach and affecting absorption.

Some blood cancers can cause mast cells to become overly activated. They may also cause an increase in tryptase, an important marker in diagnosing systemic mastocytosis.

Some other cancerous tumors like medullary thyroid carcinoma can cause mast cell type symptoms including flushing, diarrhea, and itching.

Most diseases with any allergic component can look like mast cell disease.

Eosinophilic gastrointestinal disease occurs when certain white blood cells called eosinophils become too reactive, causing inflammation to many triggers. Furthermore, people are more frequently being diagnosed with both EGID and mast cell disease.

Celiac disease is an autoimmune disease in which gluten causes an inflammatory reaction inside the body. The damage to the GI tract can be significant. Malabsorption is not unusual. Children with celiac disease may grow poorly. Bloating, diarrhea, ulceration, and abdominal pain are commonly reported.

FPIES (food protein induced enterocolitis syndrome) can cause episodes of vomiting, acidosis, low blood pressure and shock as a result of ingesting a food trigger.

Traditional (IgE) allergies can also look just like mast cell disease. They are usually distinguished by the fact that mast cell patients may react to a trigger whether or not their body specifically recognizes it as an allergen (does not make an IgE molecule to the trigger). Confusingly, it is possible to have both traditional IgE allergies and mast cell disease.

Postural orthostatic tachycardia syndrome (POTS) is commonly found in patients with mast cell disease. However, POTS itself can have similar symptoms to mast cell disease. Palpitations, blood pressure abnormalities, sweating, anxiety, nausea, and headaches are some symptoms both POTS and mast cell disease have. There are also other forms of dysautonomia which mimic the presentation of mast cell disease.

Achlorhydria is a condition in which the stomach does not produce enough acid to break down food properly. This can cause a lot of GI pain, malabsorption, anemia, and weight loss.

Hereditary angioedema and acquired angioedema are conditions that cause a person to swell, often severely. Swelling may affect the airway and can be fatal if the airway is not protected. Swelling within the abdomen can cause significant pain and GI symptoms like nausea and vomiting.

Gastroparesis is paralysis of the stomach. People with GP often experience serious GI pain, vomiting, nausea, diarrhea or constipation, bloating and swelling.

Inflammatory bowel diseases and irritable bowel syndrome can all cause GI symptoms identical to what mast cell patients experience.

This list is not exhaustive. There are many other diseases that can look similar to mast cell disease. These are the ones I have come across most commonly.

For more detailed reading, please visit the following posts:

Gastroparesis: Part 1
Gastroparesis: Treatment (part 2)
Gastroparesis: Diabetes and gastroparesis (Part 3)
Gastroparesis: Post-surgical gastroparesis (Part 4)
Gastroparesis: Less common causes (Part 5)
Gastroparesis: Autonomic nervous system and vagus nerve (Part 6)
Gastroparesis: Idiopathic gastroparesis (Part 7)

Food allergy series: Food related allergic disorders
Food allergy series: FPIES (part 1)
Food allergy series: FPIES (part 2)
Food allergy series: Eosinophilic colitis
Food allergy series: Eosinophilic gastrointestinal disease (part 1)
Food allergy series: Eosinophilic gastrointestinal disease (part 2)
Food allergy series: Eosinophilic gastrointestinal disease (part 3)
Food allergy series: Eosinophilic esophagitis (Part 1)
Food allergy series: Eosinophilic esophagitis (Part 2)
Food allergy series: Eosinophilic esophagitis (Part 3)

Angioedema: Part 1
Angioedema: Part 2
Angioedema: Part 3
Angioedema: Part 4

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 5
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 7

Food allergy series: Food related allergic disorders

The term “food allergy” is generally used by medical professionals to refer to IgE mediated allergic responses. However, it is used in a broader sense by patients who have similar conditions because the term is more likely to be understood. The truth is that there are several types of allergic disorders provoked by foods. They are all listed below and will be expounded upon in the coming days.

IgE antibodies mediate the following types of reactions. All of them have immediate onset of symptoms following interaction with the antigen.

  • Oral allergy syndrome. This presentation is usually mild. It causes itching and mild swelling in the mouth, progressing into the throat about 7% of the time, with less than 2% of cases progressing to anaphylaxis. OAS occurs due to sensitization to pollens. These pollens have specific shapes that are recognized by the IgE molecules; certain raw fruits and vegetables may shapes that are close enough to be recognized by the same IgE molecules. This is known as crossreactivity. Cooking the food changes the shapes seen by the IgE molecules and is therefore cooked forms are usually safe. In birch pollen sensitive people, apples, peaches, pears and carrots can cause crossreaction; in ragweed sensitive people, melons can be problematic. This is usually diagnosed by skin testing with the raw fruits/ vegetables. OAS can persist and be problematic during the season when the offending pollens are most prevalent.
  • Asthma irritation, including rhinitis. This can be caused by inhaling the food protein. It is most common in infants and children with the exception of work exposures in adults, like Baker’s asthma. This most commonly occurs with the eight major allergens: egg, milk, wheat, soy, peanut, tree nuts, fish and shellfish. Skin testing and serum IgE measurement can be used for diagnosis.
  • Urticaria and angioedema. This occurs when an offending food is ingested or contacts the skin (contact urticaria.) Food exposures cause 20% of acute urticaria cases and 2% of chronic urticaria cases. It is much more common in children and usually occurs after exposure to the eight major allergens. Skin testing and serum IgE measurement can be used for diagnosis.
  • GI hypersensitivity.Immediate onset vomiting can occur in response to the major food allergens. Skin testing and serum IgE measurement can be used for diagnosis.
  • Food associated, exercise induced anaphylaxis. This occurs following ingestion of food after recent completion of exercise. It is thought that exercise affects the way the GI tract absorbs and digests allergens. This most commonly affects adults, with wheat, shellfish and celery being the most common foods to provoke this reaction. Skin testing, serum IgE measurement, component testing and exercise testing can be used for diagnosis.
  • Delayed food-induced anaphylaxis to meat. This occurs several hours after ingesting the meat. It occurs when the body generates antibodies to carbohydrate a-Gal, which can be induced by tick bites. Beef, pork and lamb are known to cause reactions in a-Gal sensitive people. Testing should include serum IgE to a-Gal.
  • Anaphylaxis. I have addressed this in detail before. It can occur in response to any food, but the eight major allergens are most common. It results in massive mast cell degranulation, leading to cardiovascular collapse.

Some allergic responses to food are due to both IgE mediated reactions and delayed cell-mediated reactions.

  • Atopic dermatitis. In children with AD, about 35% of moderate/severe rashes are due to food reactions. This is thought to be due to food reactive T cells locating to the skin. It is most common in infants and least common in adults. All major allergens can be causative, but egg and milk are the most common. AD is usually self limiting. Skin testing and serum IgE measurement can be used for diagnosis.
  • Eosinophilic GI disease (EGID.) Eosinophils are inflammatory cells that share a lot of functions and behaviors with mast cells. Like mast cell disease, eosinophilic disease can affect a variety of organs, most commonly the GI tract. Symptoms are widely variable and related to level of inflammation and infiltration. It often causes difficult or painful swallowing, weight loss, obstruction and edema. EGID is related to the activity of several mediators, include IL-5, eotaxin, which causes eosinophils to home to various inflamed locations. Much like mast cell disease, it can occur in response to a wide array of foods. Elimination diets are first line treatments for EGID. Endoscopy, kin testing and serum IgE measurement can be used for diagnosis, but elimination diets are often used empirically for diagnosis.

Some allergic type responses to food are not due to IgE antibodies.

  • Food protein induced enterocolitis syndrome (FPIES.) Usually found in infants, repeat exposure to certain proteins causes chronic vomiting, diarrhea, low energy and poor growth. Exposure again following a period of abstinence from offending substance can cause vomiting, diarrhea and 15% drop in blood pressure. These reactions occur about two hours after ingestion. Cow’s milk, soy, rice and oat are the most frequently reported sources, but many others have been recorded. In FPIES children, their cells are more responsive to TNF-a and less responsive to TGF-b. FPIES usually resolves with age, but can be difficult to diagnose due to skin testing and serum IgE testing usually being negative.
  • Food protein induced allergic proctocolitis. This causes mucuosy, bloody stools as a result of eosinophilic response in infants. This occurs in response to milk through breast feeding and resolves when the substance is removed from the mother’s diet.
  • Heiner syndrome. This rare condition is marked by pulmonary infiltration, upper respiratory symptoms, iron deficiency anemia and failure to thrive. It occurs in infants and is triggered specifically by milk. It is thought that there may be a milk specific IgG reaction.
  • Celiac disease. This autoimmune disease causes malabsorption and enteropathy. It is a response to gliadin, a gluten protein in wheat and other grains. It can cause bone abnormalities, IgA deficiency, dermatitis herpetiformis and a variety of other complications. It can present at any age and is lifelong. Blood testing during food challenges, GI biopsies, and testing for HLA DQ2 and DQ8.

Cell mediated reactions are not due to IgE antibodies.

  • Allergic contact dermatitis. This type of eczema occurs in response to metals in foods. This occurs mainly in adults. It is diagnosed by atopy patch testing.

Mast cell reactions to food are related to inappropriate degranulation which has not been fully characterized. Mast cell food reactions will be discussed more completely in an upcoming post.

 

Reference:

Sicherer, Scott, Sampson, Hugh. Food allergy: Epidemiology, pathogenesis, diagnosis and treatment. J Allergy Clin Immunol 2014, 133 (2): 291-307.