Flushing disorders associated with gastrointestinal symptoms: Part 1, neuroendocrine tumors, mast cell disorders and hyperbasophila
Open accessAbstract
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.
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Most symptoms attributable to mast cell activation, such as isolated flushing, pruritus, headache, abdominal pain, or tachycardia, are not specific to mast cells but can be found in other clinical conditions and disorders.
“This is because most symptoms attributable to MCA, such as isolated fl ushing, pruritus, headache, abdominal pain, or tachycardia, are not speci fi c to MCs but can be found in other clinical conditions and disorders as well. 112-118”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [118]
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“This is because most symptoms attributable to MCA, such as isolated flushing, pruritus, headache, abdominal pain, or tachycardia, are not specific to MCs but can be found in other clinical conditions and disorders as well.(112-118) Hence, a broad range of differential diagnoses, including cardiovascular, endocrinologi…”
Background
- Authors
- Rastogi, V., Singh, D., Mazza, J. J., Parajuli, D., & Yale, S. H.
- Affiliations
- University of Central Florida (US)
- Feinstein Institute for Medical Research (US)
- Marshfield Clinic Research Foundation (US)
- University of Louisville (US)
- Corresponding author
- Yale, Steven H.
- Venue
- Clinical Medicine & Research
- Publisher
- Marshfield Clinic Research Institute
- Published
- 2018-04-12
- Volume
- 16
- Issue
- 1-2
- Pages
- 16-28
- ISSN
- 1539-4182 (ISSN-L)
- 1554-6179
- PMC
- PMC6108509
- OpenAlex
- W2798010348
- Cited by
- 32
- References
- 84
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Clinical Medicine & Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- flushing, neuroendocrine tumors, mast cell disease, carcinoid syndrome, pheochromocytoma, vasoactive intestinal peptide, medullary thyroid carcinoma, POEMS syndrome, polyneuropathy, gastrointestinal symptoms, histamine, serotonin, prostaglandins, differential diagnosis
- MeSH terms
- Adrenal Gland Neoplasms, Basophils, Carcinoid Tumor, Constipation, Diarrhea, Vipoma, Flushing, Gastrointestinal Diseases, Humans, Leukocyte Disorders, Mastocytosis, Nausea, Pancreatic Neoplasms, Pheochromocytoma, Thyroid Neoplasms, Vomiting, Abdominal Pain, POEMS Syndrome, Carcinoma, Neuroendocrine, Neuroendocrine Tumors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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