What is the differential diagnosis for a sore in the mouth of a pediatric patient?

Differential Diagnosis for Oral Sores in Pediatric Patients

The differential diagnosis for mouth sores in children is primarily divided by clinical presentation: viral infections (most common), bacterial infections, aphthous ulcers, and less commonly, systemic diseases or malignancy.

Viral Etiologies (Most Common)

Viral infections are the predominant cause of oral lesions in children and should be suspected when specific clinical features are present. 1

Herpes Simplex Virus (HSV)

• Primary herpetic gingivostomatitis presents with vesicles and ulcers, typically in younger children experiencing their first HSV infection 1
• Labial herpes may be noted in children with primary HSV infection, though less commonly than in adults 1
• Vesicular lesions that rupture into painful ulcers distinguish HSV from other causes 1

Coxsackievirus (Herpangina)

• Characteristic vesicles on the posterior pharynx and soft palate that distinguish it from other viral causes 1, 2
• Part of the hand-foot-mouth disease spectrum in some cases 1

Other Viral Causes

• Adenovirus, parainfluenza, rhinovirus, respiratory syncytial virus commonly cause pharyngitis with oral involvement 1
• Epstein-Barr virus (infectious mononucleosis) presents with pharyngitis, generalized lymphadenopathy and splenomegaly 1
• Measles, cytomegalovirus, rubella, and influenza may have associated oral manifestations 1

Bacterial Etiologies

Group A Streptococcus (GAS)

• Most common bacterial cause requiring antibiotic therapy 1
• Peak incidence in children 5-15 years of age, uncommon in children <3 years 1
• Presents with sudden-onset sore throat, fever, tonsillopharyngeal erythema with/without exudates, tender anterior cervical lymphadenopathy 1
• Key distinguishing features: absence of cough, rhinorrhea, hoarseness, conjunctivitis, or discrete ulcerative lesions strongly suggests bacterial rather than viral etiology 1
• Petechiae on the palate and scarlatiniform rash may be present 1

Other Bacterial Causes

• Arcanobacterium haemolyticum: pharyngitis with scarlet fever-like rash, particularly in teenagers 1
• Neisseria gonorrhoeae: consider in sexually active adolescents 1, 2
• Corynebacterium diphtheriae: typical membrane present 2
• Acute necrotizing ulcerative gingivitis (Vincent's angina): mixed anaerobic infection 1, 3

Aphthous Ulcers (Non-Infectious)

Aphthous ulcers are extremely painful, shallow ulcerations with erythematous halos on unattached oral mucosa (buccal mucosa, lips, tongue, soft palate). 3, 4, 5

Clinical Subtypes

• Minor aphthous ulcers (80-90% of cases): small, round/ovoid with circumscribed margins 4, 5
• Major aphthous ulcers: larger, more severe variant 6, 5
• Herpetiform aphthous ulcers: multiple small lesions 3, 5

Recurrent Aphthous Stomatitis (RAS)

• Defined as ≥4 episodes per year 3
• May be associated with celiac disease, inflammatory bowel disease, nutritional deficiencies (iron, folates), HIV infection, neutropenia 3
• Behçet's disease: recurrent bipolar aphthosis (oral and genital) 3

Critical Diagnostic Approach

When Viral Features Predominate

Do NOT test for GAS when obvious viral features are present: cough, rhinorrhea, hoarseness, conjunctivitis, oral ulcers, viral exanthem, or diarrhea. 1

When Bacterial Infection is Suspected

• Children <3 years: testing for GAS generally not indicated unless high-risk factors present (e.g., sibling with confirmed GAS) 1
• Children 5-15 years with appropriate clinical features: perform rapid antigen detection test (RADT) with backup throat culture if negative 1
• Clinical scoring alone is insufficient—only 35-50% of patients with all clinical criteria have confirmed GAS 1

Red Flags Requiring Further Investigation

• Solitary chronic ulcer: biopsy mandatory to exclude squamous cell carcinoma 3
• Solitary palatal ulcer: consider necrotizing sialometaplasia 3
• Severe recurrent lesions with immunodeficiency features: evaluate for HIV, neutropenia 3, 6
• Systemic symptoms with oral ulcers: consider inflammatory bowel disease, Behçet's disease 3

Common Pitfalls to Avoid

• Do not diagnose GAS pharyngitis clinically without testing—even experienced physicians cannot reliably distinguish bacterial from viral causes 1
• Do not perform imaging for routine pharyngitis—radiographic abnormalities are common with viral infections and lack specificity 1
• Do not use antibiotics for viral pharyngitis, common cold, or acute bronchitis—these conditions do not benefit from antibiotics 1
• Do not confuse aphthous ulcers with HSV—aphthous ulcers occur on unattached mucosa while HSV typically affects attached gingiva and hard palate 5
• Positive RADT does not require backup culture (highly specific ~95%), but negative RADT in children requires throat culture confirmation 1