What are the possible causes of lip swelling?

Causes of Lip Swelling

Lip swelling results from angioedema (allergic or hereditary), trauma, infections, inflammatory conditions (including drug reactions), vascular lesions, or systemic diseases affecting capillary hemodynamics or lymphatic drainage. 1

Primary Mechanisms of Lip Swelling

Lip swelling occurs through four fundamental pathophysiologic mechanisms 2:

• Increased capillary hydrostatic pressure from venous obstruction, deep vein thrombosis, or superior vena cava syndrome 2
• Increased capillary permeability secondary to allergic reactions, infections, or inflammation 2
• Decreased capillary oncotic pressure in cirrhosis, malnutrition, or hypoalbuminemic states 2
• Lymphatic obstruction from malignancy or primary lymphedema 2

Allergic and Immunologic Causes

Angioedema represents the most critical cause requiring immediate recognition due to potential airway compromise. 1

• IgE-mediated angioedema causes rapid lip, tongue, and facial swelling that can progress to life-threatening airway obstruction 1
• Hereditary angioedema (HAE), particularly HAE-FXII, HAE-PLG, and HAE-ANGPT1 variants, frequently manifests with recurrent facial and lip swelling 1
• Food allergy rarely causes isolated lip swelling without gastrointestinal, dermatologic, or systemic manifestations; urticarial rash, facial or lip swelling, or bronchospasm strongly suggest IgE-mediated reaction 2
• Drug hypersensitivity reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, cause painful lip erythema progressing to hemorrhagic sloughing with dark adherent crusts 1

Infectious Causes

Multiple infectious agents produce lip swelling through direct tissue invasion or inflammatory response 3, 4:

• Herpes labialis causes vesicular eruptions that may present with localized swelling before ulceration 4
• Angular cheilitis from fungal or bacterial infection produces commissural swelling with erythema and fissuring 4
• Deep fungal infections (histoplasmosis, blastomycosis, coccidiomycosis) can cause granulomatous lip lesions with swelling, particularly in immunocompromised patients 5
• Leishmaniasis should be suspected in endemic areas (including Israel) when chronic lip lesions with swelling occur 4

Inflammatory and Granulomatous Conditions

Chronic lip swelling without obvious allergic or infectious cause warrants consideration of granulomatous disease. 3, 6

• Orofacial granulomatosis presents as chronic, persistent lip swelling of unknown etiology, diagnosed by biopsy after excluding other causes 4
• Miescher syndrome (monosymptomatic Melkersson-Rosenthal syndrome) causes recurrent or persistent lip enlargement without facial palsy or fissured tongue 3
• Plasma cell cheilitis produces diffuse lip swelling with infiltration of plasma cells on histology 6
• Sarcoidosis and Wegener granulomatosis may present with lip swelling before systemic manifestations become apparent 5

Vascular and Structural Lesions

Vascular malformations and benign tumors cause localized or diffuse lip enlargement 2:

• Infantile hemangiomas (IH) of the lip cause distortion and swelling, with high risk of ulceration particularly affecting the lower lip 2
• Mucous extravasation cysts (mucoceles) present as focal, fluctuant swelling from minor salivary gland trauma 3
• Venous malformations produce soft, compressible swelling that increases with dependent positioning 3

Environmental and Traumatic Causes

Local factors frequently produce reversible lip swelling 4, 6:

• Actinic cheilitis from chronic sun exposure causes lower lip swelling, scaling, and potentially malignant transformation in light-skinned individuals 4
• Contact cheilitis (allergic or irritant) from cosmetics, dental materials, or topical medications produces localized or diffuse swelling 6
• Mechanical trauma from dental appliances, accidental biting, or sharp tooth edges causes focal swelling corresponding to the injury site 2
• Lip licking habit and mouth breathing cause chronic irritation with secondary swelling and infection risk 4

Systemic Disease Manifestations

Several systemic conditions present with lip swelling as an early or prominent feature 1, 7:

• Inflammatory bowel disease (Crohn's disease) may manifest as orofacial granulomatosis with lip swelling 2
• Lupus erythematosus and lichen planus can involve the lips with erythema, scaling, and swelling 4, 6
• Pemphigus/pemphigoid group causes bullous lesions that may present initially with lip swelling before ulceration 6
• Xerostomia from Sjögren syndrome or medications leads to dry, cracked lips with secondary swelling 6

Critical Diagnostic Red Flags

Any lip swelling persisting beyond 2 weeks or accompanied by ulceration requires biopsy to exclude malignancy. 8, 5

• Squamous cell carcinoma of the lip presents as chronic ulceration or exophytic lesion, most commonly in patients over 50 with sun exposure history 4
• Rapidly progressive swelling with airway symptoms demands immediate emergency evaluation for angioedema 1
• Unilateral chronic swelling without clear traumatic or infectious cause warrants investigation for malignancy or granulomatous disease 3
• Recurrent swelling with family history should prompt evaluation for hereditary angioedema 1