What is the differential diagnosis for a patient presenting with oral sores and swollen lips?

Differential Diagnosis for Oral Sores with Swollen Lips

The differential diagnosis for oral sores with swollen lips must prioritize life-threatening conditions first: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), followed by autoimmune bullous diseases, infectious causes, and inflammatory conditions. 1

Immediate Life-Threatening Considerations

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

• This is the most critical diagnosis to exclude due to high mortality risk. 1
• Presents with painful mucosal erythema progressing to blistering and ulceration, with hemorrhagic sloughing of the vermillion border developing dark adherent crusts 1
• Lip involvement with haemorrhagic crusting is characteristic 1
• Often associated with recent medication exposure 2
• Requires immediate hospitalization and withdrawal of causative agent 1

Erythema Multiforme

• Acute-onset condition causing rapid development of oral ulcers 3
• Can present with target lesions on skin and mucosal involvement 3
• Less severe than SJS/TEN but requires prompt recognition 3

Autoimmune and Bullous Diseases

Pemphigus Vulgaris and Mucous Membrane Pemphigoid

• These conditions require immunofluorescence testing for definitive diagnosis. 4
• Present as multiple chronic oral ulcers associated with immune system disturbances 3
• Bullae rupture rapidly in the oral environment, leaving erosions 3
• Direct immunofluorescence (DIF) on biopsy is essential for diagnosis 5

Erosive Lichen Planus

• Chronic inflammatory condition causing multiple oral ulcers 3
• Requires immunofluorescence for definitive diagnosis 4
• Associated with immune dysregulation 3

Infectious Causes

Herpes Simplex Virus (HSV)

• Primary herpetic gingivostomatitis causes severe oral ulceration with lip swelling. 6
• Recurrent herpes labialis ("cold sores") typically affects the vermillion border 3, 7
• HSV lesions begin as vesicles that rupture, leaving painful ulcers 3
• Can be distinguished from aphthous ulcers by location: HSV affects keratinized mucosa (lips, gingiva), while aphthae affect non-keratinized mucosa 3

Acute Necrotizing Ulcerative Gingivitis (ANUG)

• Causes rapid-onset multiple oral ulcers 3
• Associated with poor oral hygiene and immunosuppression 3

Oral Candidiasis

• Can present with white curd-like material and underlying erosions 8
• More common in immunocompromised patients or those on chronic steroids 8
• May cause lip swelling and crusting when involving perioral skin 8

Syphilis

• Can present with oral ulceration 1
• Requires serological testing for diagnosis 1, 5

Tuberculosis

• Presents with stellate ulcers with undermined edges 1
• Requires high index of suspicion and specialized testing 1

Inflammatory and Systemic Conditions

Crohn's Disease and Orofacial Granulomatosis

• Oral ulcers may be the presenting feature of inflammatory bowel disease. 1
• Lip swelling is characteristic of orofacial granulomatosis 2
• Requires gastrointestinal evaluation if suspected 1

Recurrent Aphthous Stomatitis (RAS)

• Most common cause of recurrent oral ulcers 1, 5
• Presents as well-demarcated, oval/round ulcers with white/yellow pseudomembrane and erythematous halo 1, 5
• Affects non-keratinized mucosa (buccal, labial mucosa, tongue) 3
• Does not typically cause significant lip swelling unless severe 1

Allergic Contact Cheilitis

• Causes lip swelling with possible erosions 2
• Related to allergen exposure (cosmetics, dental materials, foods) 2

Hematologic and Nutritional Causes

Blood Disorders

• Leukemia, anemia, and neutropenia can present with oral ulceration. 1, 5
• Neutropenia causes widespread necrotic ulcers 1
• Requires full blood count for screening 1, 5

Nutritional Deficiencies

• Iron, folate, and vitamin B12 deficiency can cause oral ulceration 5
• Should be tested in recurrent cases 5

Malignancy

Squamous Cell Carcinoma

• Must be excluded in any persistent solitary ulcer. 3
• Typically presents as non-healing ulcer with indurated borders 3

Lymphoma

• Can present as oral ulceration with necrosis 1
• NK/T-cell lymphoma characteristically affects palate and gingiva 1

Diagnostic Algorithm

Initial Assessment

• Document precise location, duration, size, shape, and number of ulcers 4, 5
• Check for vesicles or bullae (may rupture rapidly) 4, 3
• Assess for extraoral manifestations (skin lesions, systemic symptoms) 4, 3
• Obtain detailed medication history to identify drug-induced causes 1, 2

First-Line Laboratory Testing

• Full blood count to exclude leukemia, anemia, neutropenia 1, 4, 5
• Fasting blood glucose to identify diabetes (predisposes to fungal infection) 1, 5
• HIV antibody and syphilis serology 1, 4, 5
• Blood coagulation studies if biopsy planned 1

Biopsy Indications

• Mandatory if ulcers persist beyond 2 weeks without clear diagnosis 4, 5
• Multiple biopsies needed when ulcers have different morphological characteristics 1, 4
• Include direct immunofluorescence if bullous disease suspected 4, 5
• Send tissue for culture if infection suspected 1

Second-Line Testing (if diagnosis remains unclear)

• Nutritional screening: iron, folate, vitamin B12 5
• Autoimmune markers if autoimmune disease suspected 5
• Specific antibody tests (Dsg1, Dsg3, BP180, BP230) for bullous diseases 5
• Bone marrow biopsy if hematologic malignancy suspected 1

Critical Pitfalls to Avoid

• Never delay biopsy beyond 2 weeks for persistent ulcers—malignancy and serious systemic diseases must be excluded 4, 5
• Do not overlook systemic associations: multiple oral ulcers may indicate Crohn's disease, blood disorders, or autoimmune conditions 4, 5
• Do not rely solely on clinical appearance without appropriate testing 5
• Do not miss drug-induced causes, particularly SJS/TEN from recent medication exposure 1, 2
• Do not confuse HSV with aphthous ulcers—location is key (keratinized vs. non-keratinized mucosa) 3
• Do not treat symptoms without establishing definitive diagnosis for persistent ulcers 5

When to Refer

• Immediate referral if SJS/TEN suspected 1
• Refer to oral medicine specialist if ulcers persist beyond 2 weeks or do not respond to initial treatment 5
• Coordinate multidisciplinary care: gastroenterology for IBD-related ulcers, hematology for blood disorders 5