Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila

Clin Med Res. 2018 Jun;16(1-2):16-28. doi: 10.3121/cmr.2017.1379a. Epub 2018 Apr 12.


Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.

Keywords: Flushing; Gastrointestinal; Neuroendocrine Tumor; Systemic Mastocytosis; human.

Publication types

  • Review

MeSH terms

  • Abdominal Pain / etiology
  • Adrenal Gland Neoplasms / complications
  • Adrenal Gland Neoplasms / diagnosis
  • Adrenal Gland Neoplasms / therapy
  • Basophils*
  • Carcinoid Tumor / complications
  • Carcinoid Tumor / diagnosis
  • Carcinoid Tumor / therapy
  • Carcinoma, Neuroendocrine / complications
  • Carcinoma, Neuroendocrine / diagnosis
  • Carcinoma, Neuroendocrine / therapy
  • Constipation / etiology
  • Diarrhea / etiology
  • Flushing / etiology*
  • Gastrointestinal Diseases / etiology*
  • Humans
  • Leukocyte Disorders / complications*
  • Leukocyte Disorders / diagnosis
  • Leukocyte Disorders / therapy
  • Mastocytosis / complications*
  • Mastocytosis / diagnosis
  • Mastocytosis / therapy
  • Nausea / etiology
  • Neuroendocrine Tumors / complications*
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / therapy
  • POEMS Syndrome / complications*
  • POEMS Syndrome / diagnosis
  • POEMS Syndrome / therapy
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / therapy
  • Pheochromocytoma / complications
  • Pheochromocytoma / diagnosis
  • Pheochromocytoma / therapy
  • Thyroid Neoplasms / complications
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / therapy
  • Vipoma / complications
  • Vipoma / diagnosis
  • Vipoma / therapy
  • Vomiting / etiology

Supplementary concepts

  • Thyroid cancer, medullary