Oral Ulcer Differential Diagnosis and Complement System Functions

Differential Diagnosis of Oral Ulcers and Vesiculobullous Lesions

Classification by Number and Etiology

• Single Ulcers: Traumatic, Tuberculosis (TB), Primary Syphilis.
• Multiple Ulcers: Recurrent Aphthous Stomatitis, Herpetic Stomatitis, Erythema Multiforme, Pemphigus Vulgaris.

Classification by Location

• Keratinized Mucosa: Recurrent Intraoral Herpes, Mucous Membrane Pemphigoid, Major Aphthous Ulcers.
• Non-Keratinized Mucosa: Minor Aphthous Ulcers, Herpetiform Ulcers.

Classification by Clinical Features

• Ulcers Causing Scarring: Major Aphthous Ulcers, Mucous Membrane Pemphigoid Ulcers, Tertiary Syphilis.
• Painless Ulcers: Tuberculosis (TB), Primary Syphilis, Tertiary Syphilis.
• Painful Ulcers: Primary Herpetic Gingivostomatitis, Recurrent Intraoral Herpes, Herpes Zoster, Ramsay Hunt Syndrome, Traumatic Ulcers, Aphthous Ulcers, Pemphigus Vulgaris, Mucous Membrane Pemphigoid.

Classification by Vesicle Formation Mechanism

• Ulcers Due to Intraepithelial Vesicles: Pemphigus Vulgaris, Herpes Simplex Lesions, Varicella-Zoster Infection.
• Ulcers Due to Subepithelial Vesicles: Mucous Membrane Pemphigoid, Erythema Multiforme, Bullous Lichen Planus.

Vesiculobullous Diseases

Infective Vesiculobullous Diseases

• Herpes Simplex Virus (HSV)
• Varicella-Zoster Virus (VZV)
• Hand-Foot-and-Mouth Disease (Coxsackie A)

Non-Infective Vesiculobullous Diseases

• Pemphigus Vulgaris
• Mucous Membrane Pemphigoid
• Erythema Multiforme

Associated Signs and Syndromes

• Bloody Crusted Lip: Pemphigus Vulgaris, Erythema Multiforme.
• Nikolsky Sign (Positive): Erythema Multiforme, Pemphigus Vulgaris, Mucous Membrane Pemphigoid.
• Lipschutz Bodies (Viral Inclusion Bodies): Herpes Simplex, Herpes Zoster, Mucous Membrane Pemphigoid.
• Mucocutaneous Ocular Syndromes: Behçet’s Disease, Reiter’s Disease (Reactive Arthritis), Stevens-Johnson Syndrome.

Biological Significance of Complement Activation

The complement system plays a crucial role in innate immunity and inflammation. Its activation leads to several key biological functions:

1. Complement-Mediated Inflammation (Anaphylatoxins)

   Components C3a, C4a, and C5a are known as Anaphylatoxins. They activate mast cells and basophils, causing the release of histamine and promoting inflammation.

2. Complement-Mediated Cell Adherence

   Complement receptors (e.g., CR1) are found on neutrophils, macrophages, and B-lymphocytes. CR1 strongly binds to particles coated with C3b, facilitating cell adherence and subsequent phagocytosis.

3. Complement-Mediated Opsonization

   Opsonization enhances phagocytosis. C3b has the most important opsonizing activity, tagging pathogens for destruction.

4. Complement-Mediated Chemotaxis

   • C5a is the most important chemotactic factor for neutrophils, macrophages, and eosinophils.
   • C3a is chemotactic for eosinophils.
   • The C5b67 part of the Membrane Attack Complex (MAC) is chemotactic for neutrophils and eosinophils.

5. Complement-Mediated Clearance of Immune Complexes

   This function involves the scavenger action of macrophages, which remove immune complexes tagged by complement components.