What is the differential diagnosis for unilateral facial swelling and how should it be worked up?

Differential Diagnosis for Unilateral Facial Edema

Unilateral facial edema typically indicates a localized pathological process requiring prompt evaluation, with the most common etiologies being infectious, traumatic, neoplastic, or inflammatory conditions. 1

Key Clinical Distinctions

The rapidity of onset is crucial for narrowing your differential:

• Acute onset (< 72 hours) suggests infection, trauma, or allergic reaction 1
• Gradual onset over days to weeks points toward chronic conditions or neoplastic processes 2
• Unilateral presentation indicates localized pathology, whereas bilateral involvement suggests systemic disease 1

Primary Differential Diagnoses

Infectious Causes

Odontogenic infection is the most common etiology of facial swelling in dental emergency patients 3

• Look for intraoral findings, dental caries, periodontal disease, or obvious "sore thumb" causative tooth 3
• Associated erythema, warmth, and tenderness strongly suggest bacterial infection 1
• Acute sinusitis can present with unilateral facial pain, swelling, and fever—particularly when complicated by invasive fungal disease in immunocompromised patients 4

Invasive fungal rhinosinusitis presents with facial pain, facial swelling, nasal obstruction, and fever in 50-65% of immunocompromised patients 4

• Endoscopic appearance of necrosis (especially middle turbinate) is a hallmark sign 4
• Unilateral disease on radiology is typical 4
• Requires immediate biopsy showing hyphal forms within sinus mucosa, submucosa, blood vessels, or bone for diagnosis 4

Parinaud oculoglandular syndrome causes unilateral granulomatous follicular conjunctivitis with ipsilateral regional lymphadenopathy, fever, and eyelid swelling 4

• Most commonly from cat scratch disease (Bartonella henselae) or tularemia 4

Epstein-Barr virus infection can rarely present as unilateral facial swelling with persistent oral mucosal ulcers and fever, confirmed by tissue genomics sequencing 5

Traumatic Causes

Facial trauma with underlying fractures (particularly frontal bone) requires immediate CT imaging 1

• Blunt or penetrating injury causes localized edema 1
• Temporal bone fractures can produce facial nerve paralysis with associated swelling 2
• Post-surgical edema following facial procedures is typically self-limiting 1

Neoplastic Causes

Tumors or neoplastic processes present with slowly progressive unilateral swelling over days to weeks 2

• Parotid tumors, facial schwannomas, meningiomas, and cholesteatomas can involve facial structures 2
• Ocular surface squamous neoplasia may present with conjunctival hyperemia and localized edema 1
• Multiple myeloma can rarely manifest as unilateral facial swelling 6
• Rapidly progressive swelling with cranial nerve deficits in children suggests rhabdomyosarcoma, Langerhans cell histiocytosis, Ewing sarcoma, or metastatic neuroblastoma 7

Inflammatory/Systemic Causes

Sarcoidosis can cause granulomatous inflammation of facial structures 2

Angioedema from allergic reactions presents with acute onset but is typically bilateral rather than unilateral 1

Diagnostic Workup Algorithm

Step 1: Focused History and Physical Examination

Document the following specific findings:

• Onset timing: Acute (< 72 hours) versus gradual (days to weeks) 1, 2
• Associated symptoms: Fever, pain, visual changes, numbness, motor weakness 4, 1
• Erythema, warmth, or tenderness indicating inflammation or infection 1
• Facial asymmetry, scarring, or malfunction (poor blink, lid closure) 1
• Proptosis, blepharoptosis, lagophthalmos suggesting orbital involvement 1
• Forehead involvement: If facial droop includes forehead, this indicates peripheral facial nerve lesion rather than central stroke 2
• Ear canal inspection for vesicular rash (Ramsay Hunt syndrome) 2
• Intraoral examination for dental pathology 3
• Nasal endoscopy for necrotic tissue if invasive fungal disease suspected 4

Step 2: Imaging Strategy

For suspected infection or trauma:

• Contrast-enhanced CT is the modality of choice for detecting abscesses requiring surgical drainage and evaluating facial trauma 1, 7
• CT imaging is essential when facial trauma is suspected, particularly with tenderness over the frontal bone 1

For suspected neoplasm or atypical presentations:

• MRI of the brain with contrast is first-line to assess the facial nerve pathway from brainstem to peripheral branches 2, 8
• MRI provides superior soft tissue resolution for identifying tumors, demyelinating lesions, vascular compression, and inflammatory processes 8
• High-resolution temporal bone CT should be added to characterize bony integrity, fractures, and canal involvement 2, 8

For suspected invasive fungal disease:

• MRI with loss of contrast enhancement is more sensitive (86%) than CT (69%) in detecting invasive fungal disease 4
• Unilateral disease on radiology is typical 4

Step 3: Laboratory Testing (Selective)

• Lyme serology only in endemic areas with appropriate exposure history 2, 8
• ESR/CRP in patients > 50 years with temporal headache or jaw claudication to screen for giant cell arteritis 2, 8
• Serum PCR and/or galactomannan for invasive aspergillosis (when both negative, NPV is 100%; when both positive, PPV is 88%) 4
• Blood cultures if systemic infection suspected 4

Step 4: Tissue Diagnosis When Indicated

Nasal-sinus biopsy should be obtained to:

• Determine if a lesion is neoplastic 4
• Confirm invasive fungal disease (showing hyphal forms within tissue) 4
• Confirm granulomatous disease when diagnosis is unclear 4

Frozen section analysis during surgery can rapidly define invasive fungal disease 4

Conjunctival or facial mass biopsy for suspected neoplasm 1

Red Flags Requiring Urgent Evaluation

• Visual changes or eye pain warrant urgent ophthalmologic evaluation 1
• Facial swelling with redness is atypical for Bell's palsy and mandates investigation for infectious causes 2
• Additional neurologic signs (dizziness, dysphagia, diplopia) suggest brainstem pathology requiring urgent MRI 2, 8
• Bilateral facial involvement is never idiopathic and requires evaluation for Lyme disease, sarcoidosis, or Guillain-Barré syndrome 2
• Persistent or progressive symptoms beyond 2-4 months warrant imaging even if initially thought benign 2, 8
• Endoscopic appearance of necrosis in immunocompromised patients requires immediate biopsy for invasive fungal disease 4
• Rapidly progressive swelling with cranial nerve deficits in children suggests aggressive malignancy 7

Common Pitfalls to Avoid

• Assuming all acute facial swelling is odontogenic infection—approximately 30% have alternative etiologies requiring different management 2, 3
• Overlooking potential ocular involvement, which may lead to vision-threatening complications 1
• Using routine non-contrast CT head or CTA head alone for facial nerve evaluation—these are insufficient and should not be used as isolated studies 2
• Giving steroids alone for infection-related facial swelling—treat the underlying infection first 2
• Delaying biopsy in immunocompromised patients with suspected invasive fungal disease, as early diagnosis is critical for prognosis 4