Noncarcinoid flushing is characterized by episodic erythema and warmth of the head, neck, and arms. Flushing is caused by rapid vasodilation in the skin, typically mediated through either the autonomic nervous system or vasoactive molecules.
Flushing can be constant or episodic. Vasoactive mediators, either endogenous or medications, are usually the cause of episodic flushing. Flushing due to autonomic causes is often associated with sweating. Patients with persistent flushing may have fixed facial erythema with telangiectasias. Rarely, patients can develop a cyanotic change, which is caused by large cutaneous blood vessels that contain slow-flowing deoxygenated blood.
Initial history and physical is important and may give the diagnosis before any tests are ordered. Some common causes that do not require additional testing include rosacea, fever, emotional flushing, menopause ("hot flashes"), anaphylaxis, diet, or medication or alcohol (see drug-induced flushing reaction).
Anaphylaxis is a can't-miss diagnosis and should always be in the differential diagnosis of a patient presenting with acute hypotension, difficulty breathing, and angioedema.
Mastocytosis (urticaria pigmentosa, mastocytoma, diffuse cutaneous mastocytosis) is an important diagnosis to consider in children with flushing, especially if these flushing episodes are associated with hypotension.
R23.2 – Flushing
238810007 – Flushing
Differential Diagnosis & Pitfalls
- Benign cutaneous flushing – Caused by emotion, temperature, food, or beverages.
- Alcohol – May cause flushing directly or via its metabolite acetaldehyde. More common among patients of Asian ancestry who may have aldehyde dehydrogenase-2 deficiency. Certain drugs combined with alcohol may cause flushing.
- Drug-induced flushing – See list below.
- Menopause – Can be provoked by warmth, hot drinks, alcohol, and mental stress.
- Cluster headache
- Carcinoid / neuroendocrine
- Medullary carcinoma of the thyroid (see thyroid cancer)
- Renal cell carcinoma
- Pancreatic cell tumor (VIPoma) – History usually includes watery diarrhea.
- Mastocytosis – An important consideration in the pediatric population.
- Serotonin syndrome
- Parkinson disease
- Multiple sclerosis
- Autonomic hyperreflexia
- Trigeminal neuralgia
- Horner syndrome
- Frey syndrome
- Scombroid – Results from improper refrigeration of fish.
- Psychiatric or anxiety disorders
- Dumping syndrome
- Vasodilators – nitroglycerin and nitric oxide releasers, sildenafil citrate, amyl nitrite, butyl nitrite
- Calcium channel blockers
- Oral steroids
- Beta blockers
- Angiotensin-converting enzyme (ACE) inhibitors
- Cholinergic drugs
- Chemotherapeutics – tamoxifen, cyclosporine doxorubicin, mithramycin, dacarbazine, cisplatin, interferon alfa-2, flutamide
- Contrast media