Flushing Syndromes Differential & Mastocytosis

Flushing has a fairly short differential:

1. Menopause
2. Carcinoid
3. Mastocytosis
4. Anaphylaxis
5. Pheochromocytoma
6. Neurologic flushing
7. Reaction to alcohol, drugs, food additives, eating
8. Medullary carcinoma of the thyroid
9. Pancreatitic islet-cell tumors
10. Renal cell carcinoma

Taking the flushing in context with his other symptoms, as well as the “spell-like” nature of his disease, we may narrow this further to carcinoid, mastocytosis and pheochromocytoma.

The following grouping has been suggested by Young WF, Maddox DE. “Spells: in search of a cause. Mayo Clin Proc. 1995; 70:757-65.” (In bold are his symptoms).

 

Carcinoid syndrome

1. Flushing
2. Diarrhea
3. Cardiac valvular disease-pulmonic stenosis, tricuspid insufficiency
4. Bronchoconstriction
5. Hypotension
6. Mild and typically asymptomatic
7. Rarely hypertension
8. Precipitated by: anxiety, ethanol, catecholamines, chocolate

 

Pheochromocytoma

1. Pain -headache most common, chest pain, abdominal pain
2. Diaphoresis
3. Palpitations
4. Hypertension (rarely shock)
5. Pallor (flushing uncommon)
6. Precipitated by: posture change. increased intra-abdominal pressure,
7. anxiety, exercise

 

Systemic mastocytosis

1. Flushing
2. Hypotension
3. Pallor, if abrupt hypotension
4. Hypertensive subset (PGF)
5. Syncope or near-syncope
6. Chest pain
7. Gastrointestinal distress
8. Pruritus
9. Precipitated by: heat, exercise, anxiety. ethanol, histamine-releasing
10. drugs

 

 

What is mastocytosis?

1. Clonal expansion of mast cells, most often indolent
2. Usually seen in bone marrow and in the normal peripheral distribution sites of these cells (skin, GI, spleen, liver.)
3. Men more often affected than women.

Classification of Mastocytosis:

1. Cutaneous
2. Indolent (normal life expectancy; 1-5% progress)
3. Systemic Mastocytosis with associated clonal heme non mast cell lineage (SM-AHNMD)
4. Aggressive Systemic Mastocytosis
5. MC leukemia
6. MC sarcoma

Clinical Manifestations of Mastocytosis:

1. Mast cells release bioactive substances resulting in:
   • pruritis
   • flushing
   • palpitations
   • vascular collapse
   • GI distress, lower abdominal cramping
   • recurrent headaches
2. Mast cell mass can occupy a space causing symptoms
3. Tissue response to the mass or substances can lead to fibrotic chances in liver, spleen, bone marrow
4. Idiosyncratic reaction to NSAIDs, ETOH, narcotics 

 

 

Diagnosis requires tissue.

1. Either one major or three minor criteria are required for diagnosis
2. Major criteria: multifocal dense infiltrates of mast cells in the bone marrow or extracutaneous tissue with confirmation by immunodetection of tryptase
3. Minor criteria:
1. Abnormal mast cell morphology
2. Aberrant mast cell surface phenotype expression of CD2, CD 25, c-kit
3. Detection of codon 816 mutation in peripheral blood cells or BM or lesional tissue
4. Total serum tryptase (alpha) >20ng/mL

 

Treatment: is awesome!

1. H1 blockers for flushing and pruritis e.g. cetirizine
2. H2 blockers or ppi for gastric hypersecretion e.g. cimetidine
3. Oral cromolyn sodium for diarrhea and abdominal pain (inhibitis mast cell degranulation)
4. ASA for severe flushing not responsive to H1, H2 blockers- only if they tolerate NSAIDs
5. Systemic steroids can help with malabsorption
6. Treat osteoporosis if present
7. Does not respond to imatinib
8. Avoid triggers for mast cell degranulation , such as ETOH, stress, allergens
9. Make sure they have an epi-pen, medi-alert bracelet

 

(Katharine Cheung MD, 12/13/10)