Mast cell look alikes

Mast cell disease is underdiagnosed in part because many of the symptoms are so common.  Even when it is recognized that a patient has multisystem involvement, there are several other conditions that need to be ruled out as they have many of the same symptoms.  Differential diagnosis is the process by which conditions that could cause a group of symptoms are identified.  The conditions listed below are in the differential diagnosis for mast cell disease.

Carcinoid tumors are slow-growing neuroendocrine tumors.  When found in certain parts of the GI system, they can cause wide ranging symptoms.  About 10% of these tumors release excessive amounts of hormones, particularly serotonin.  This action causes flushing, diarrhea, wheezing, abdominal pain and peripheral edema.  Carcinoid tumors can be distinguished from mast cell disease by doing a 24-urine test for 5-hydroxyindoleacteic acid (5-HIAA), which is a metabolite of serotonin.

Pheochromocytomas are neuroendocrine tumors of the adrenal gland.  They secrete very high amounts of norepinephrine and lesser amounts of epinephrine and other catecholamines. These tumors cause excessive activation of the sympathetic nervous system, including burning/crawling/stinging skin, flank pain, rapid heartbeat, high blood pressure, orthostatic hypotension, palpitations, anxiety, sweating, headache, paleness, weight loss, amyloid depositions and high blood sugar.  Again, 24-hour urine testing is key for diagnosis.  These tests look at the levels of catecholamines and metanephrines, breakdown products of norepinephrine and epinephrine.

Medullary thyroid cancer is formed in cells that produce the hormone calcitonin.  It causes severe diarrhea, flushing and itching.  It may occur along with cancer of the parathyroid gland and/or pheochromocytomas.  It can be diagnosed by measuring serum calcitonin, which will be elevated.

Dysautonomia is dysfunction of the autonomic nervous system, which regulates many of the involuntary functions of the body, like digestion, heart rate, and breathing.  Dysautonomia can have a wide range of symptoms, including fatigue, excess thirst, orthostatic hypotension, slow or fast heart rate, shortness of breath with exertion, blood pressure variations, swelling of the abdomen, gastroparesis, and heat intolerance, among others.  POTS is a type of dysautonomia.  It is important to realize that patients with  mast cell disease often have POTS, but it should be ruled out as the primary cause of symptoms.   There are several tests for dysautonomia, depending on the organ systems affected.

Primary asthma also needs to be ruled out as the cause of airway inflammation.  Asthma causes wheezing, coughing and shortness of breath.  It has significant overlap with mast cell respiratory symptoms and may be treated the same way. 

Vocal cord dysfunction can cause partial or full closure of the vocal folds, which can obstruct the airway.  It can cause difficulty breathing, wheezing, coughing, tightness in the chest, skin discoloration and even loss of consciousness.  VCD can look very much like anaphylaxis.  This often occurs alongside asthma.  Looking at the vocal cords with a camera can help the diagnosis.

Angioedema causes sudden swelling that usually affects the face, extremities, GI tract and airway.  There are multiple hereditary types, caused by complement dysfunction or overactive kininogenase.  Levels of complement 4 and C1 inhibitor are tested for diagnosis.  It can also be acquired by use of certain medications, including ACE inhibitors.  Plasma bradykinin is tested when ACE inhibitor associated angioedema is suspected.  (Stay tuned for a more thorough angioedema post.)

Irritable bowel syndrome is a diagnosis of exclusion.  It is considered a functional disease with no obvious organic cause.  Patients often have abdominal pain, feeling of incomplete defecation, bloating, distended abdomen, and diarrhea or constipation or both.  Complicating the issue for mast cell patients is that IBS often cooccurs with anxiety, GERD, chronic fatigue syndrome, fibromyalgia, and other conditions, which together form a constellation of issues similar to mast cell disease.

Most people eventually diagnosed with mast cell disease were previously diagnosed with anxiety or panic attacks.  Panic attacks can cause palpitations, sweating, shaking, shortness of breath, chest pain, feeling of choking, nausea, abdominal pain, chills, hot flashes, and sense of impending doom.  Further confusing the issue is the fact that mast cell disease can cause psychiatric symptoms, including anxiety.  Again, it needs to be ruled out as the primary cause of symptoms.  For mast cell patients, amelioration of symptoms with epinephrine and antihistamines is considered demonstrative that anxiety is not the primary disease process.

There are other “look alikes,” including Lyme disease, but these are the most common.