What are the possible causes of facial flushing involving the nose, cheeks, and ears?

Facial Flushing Involving Nose, Cheeks, and Ears: Causes and Clinical Approach

Immediately Exclude Life-Threatening Anaphylaxis

Anaphylaxis must be ruled out first in any patient presenting with acute facial flushing. Anaphylaxis is distinguished from other flushing causes by the presence of urticaria, angioedema, pruritus, and tachycardia (not bradycardia), and requires immediate intramuscular epinephrine 0.3 mg to the mid-outer thigh—delayed administration increases mortality risk 1, 2.

• Anaphylaxis is highly likely if acute onset skin/mucosal involvement occurs with either respiratory compromise or reduced blood pressure, or if two or more organ systems are involved rapidly after allergen exposure 2.
• Do not rely solely on tryptase or histamine levels to rule out anaphylaxis, as these may be normal despite true anaphylactic reactions 2.

Exclude Serious Endocrine and Neoplastic Causes

After excluding anaphylaxis, systematically evaluate for potentially life-threatening endocrine tumors that present with episodic flushing 1, 3, 4:

Carcinoid Syndrome

• Measure serum serotonin and 24-hour urinary 5-hydroxyindoleacetic acid 1, 2.
• Flushing in carcinoid syndrome is typically episodic and may be accompanied by diarrhea and bronchospasm 3, 4.

Pheochromocytoma

• Obtain plasma-free metanephrine and urinary vanillylmandelic acid 1, 2.
• Flushing episodes are typically accompanied by severe headache, palpitations, and hypertension 3, 4.

Mastocytosis

• Obtain serum tryptase levels 15 minutes to 3 hours after symptom onset 2.
• Persistent facial flushing can be an unusual but important clinical finding in telangiectasia macularis eruptiva perstans, a rare mast cell disorder 5.

Common Benign Causes

Rosacea (Most Common Dermatologic Cause)

Rosacea is the most likely diagnosis when persistent centrofacial erythema involves the nose, cheeks, and ears with telangiectasia and a history of easy flushing triggered by specific factors. The presence of persistent centrofacial erythema with periodic intensification by trigger factors meets minimum diagnostic criteria 6.

• Characteristic findings include erythema, telangiectasia, papules, pustules, prominent sebaceous glands, and rhinophyma, with centrofacial distribution being essential for diagnosis 2, 6.
• Telangiectasia and ectasia on the cheeks, nose, and ears represent major features, though not independently diagnostic 6.
• More frequently observed in fair-skinned individuals but occurs in all skin types 2.
• Critical pitfall: Rosacea is challenging to diagnose in darker skin tones because telangiectasia and facial flushing are difficult to visualize—emphasize hyperpigmentation and burning/stinging symptoms in these patients 2, 7.

Ocular Rosacea Considerations

• Evaluate for ocular involvement immediately, as ocular rosacea commonly accompanies cutaneous disease and can lead to sight-threatening complications if untreated 6.
• Ask about eye symptoms such as burning, stinging, dryness, foreign body sensation, or recurrent styes 6.
• Do not dismiss recurrent styes as benign in children—they may represent early ocular rosacea before facial manifestations appear 2, 7.
• Children with ocular rosacea can develop serious complications including corneal melting and perforation more frequently than adults 7.

Medication-Induced Flushing

Several medications commonly cause facial flushing involving the nose, cheeks, and ears 1, 2:

• Niacin is one of the most common medication causes of flushing 1, 2.
• Nicotine, catecholamines, and ACE inhibitors frequently induce flushing 1, 2.
• Vancomycin causes "red man syndrome" with characteristic flushing 1.
• Alcohol induces flushing, particularly in individuals with ALDH2 deficiency 2.
• Systemic retinoids (isotretinoin) increase Staphylococcus aureus colonization and cause blepharitis—discontinuation leads to improvement 2, 7.
• Dupilumab (for atopic dermatitis) causes conjunctivitis, keratitis, and blepharitis in 32-55% of patients 2, 7.

Alcohol-Induced Flushing (ALDH2 Deficiency)

• The ALDH2*2 genetic variant produces inactive aldehyde dehydrogenase 2 enzyme, preventing acetaldehyde metabolism and causing systemic accumulation with characteristic flushing, tachycardia, palpitations, and reduced alcohol tolerance 2.
• Individuals with ALDH2*2 who continue drinking despite flushing have increased risk of alcohol-associated liver disease 2.
• Complete alcohol abstinence is the definitive management for ALDH2-deficient individuals 2.

Additional Causes to Consider

Dermatologic Conditions Mimicking Rosacea

• Contact dermatitis (irritant or allergic) of the face can present with erythema, edema, and scaling 1.
• Nickel is the most common contact allergen, affecting about 10% of women with pierced ears 1.
• Seborrheic dermatitis presents with greasy yellowish scaling, itching, and inflammation on the central face and ears 1.
• Eczema (atopic dermatitis) presents with chronic pruritus, erythema, and xerotic scaling 1.

Sarcoidosis

• Lupus pernio of the external nose, face, and ears often accompanies sinonasal sarcoidosis 1.
• Nasal involvement occurs in approximately 3-4% of patients with generalized sarcoidosis, presenting with blockage, crusting, and bleeding 1.
• Hypercalcemia occurs in 10-13% of cases and raised angiotensin-converting enzyme in 60-83% 1.

Food-Related Causes

• Scombroid fish poisoning from histamine in spoiled fish causes flushing that can be more of a sunburn-like flush than urticaria 1, 2.
• Monosodium glutamate can induce postprandial flushing reactions 1.

Physiologic and Environmental Factors

• Menopausal hot flushes are a common cause of episodic facial flushing in perimenopausal women 3, 8.
• Environmental factors including reduced humidity, increased wind, drafts, air conditioning, or heating may exacerbate flushing 2.
• Emotional stress and fever can trigger physiologic flushing 8, 9.

Clinical Approach Algorithm

1. First: Exclude anaphylaxis by assessing for urticaria, angioedema, respiratory compromise, or hypotension 1, 2.

2. Second: If episodic flushing with systemic symptoms, obtain laboratory studies to exclude carcinoid syndrome (serum serotonin, urinary 5-HIAA), pheochromocytoma (plasma-free metanephrine), and mastocytosis (serum tryptase) 1, 2, 3, 4.

3. Third: If persistent centrofacial erythema with telangiectasia and history of trigger-induced flushing, diagnose rosacea and evaluate for ocular involvement 2, 6.

4. Fourth: Review all medications, particularly niacin, ACE inhibitors, vancomycin, isotretinoin, and dupilumab 1, 2.

5. Fifth: Assess alcohol consumption patterns and consider ALDH2 deficiency if flushing occurs consistently with alcohol 2.

6. Sixth: If symptoms are not progressive and serious causes are excluded, reassure the patient about the benign nature to avoid unnecessary studies 3.