What could be causing blistering on a patient's tongue?

Differential Diagnosis of Tongue Blistering

The most likely causes of tongue blistering include angina bullosa hemorrhagica (benign blood blisters), autoimmune blistering diseases (pemphigus vulgaris), Stevens-Johnson syndrome/toxic epidermal necrolysis, herpes simplex virus infection, or traumatic injury. The specific diagnosis depends on clinical presentation, timing, associated symptoms, and patient history.

Immediate Assessment Priorities

Key Historical Features to Obtain

• Onset and duration: Sudden onset within 24-48 hours suggests angina bullosa hemorrhagica or trauma; 1-6 weeks after new medication suggests drug hypersensitivity 1
• Medication history: Recent initiation of antiretrovirals (especially NNRTIs like nevirapine), anticonvulsants, or antibiotics increases risk of Stevens-Johnson syndrome 1
• Associated symptoms: Fever, constitutional symptoms, skin rash, or eye involvement suggests severe drug reaction requiring urgent care 1
• Trauma history: Recent dental procedures, eating hard foods, or use of topical anesthetics may cause traumatic blistering 2, 3
• Systemic disease: Diabetes, immunosuppression, or steroid inhaler use increases risk of angina bullosa hemorrhagica 3

Critical Physical Examination Findings

• Blister characteristics: Blood-filled blisters suggest angina bullosa hemorrhagica; clear fluid with easy rupture suggests pemphigus vulgaris 1, 3, 4
• Distribution: Isolated tongue lesion favors benign causes; extensive oral, lip, and skin involvement suggests Stevens-Johnson syndrome or pemphigus 1
• Mucosal appearance: Erythematous base with hemorrhagic crusting on lips suggests Stevens-Johnson syndrome; normal surrounding mucosa suggests angina bullosa hemorrhagica 1, 3, 4
• Lymphadenopathy: Presence suggests malignancy, infection, or systemic disease 1

Most Likely Diagnoses by Clinical Pattern

Benign Blood Blisters (Angina Bullosa Hemorrhagica)

• Sudden onset of painless, tense, dark red blood-filled blister that ruptures spontaneously within 24-48 hours 3, 4
• Affects middle-aged and elderly patients without gender predilection 4
• No systemic symptoms, blood dyscrasias, or other vesicular-bullous disorders 3
• No treatment required; reassurance only 3, 4

Autoimmune Blistering Disease (Pemphigus Vulgaris)

• Oral mucosa is first site in majority of cases, with fragile blisters that rupture easily leaving painful erosions 1
• May remain confined to oral cavity or extend to skin after average 4-month lag period 1
• Requires perilesional biopsy for histology and direct immunofluorescence showing IgG deposition on keratinocyte cell surfaces 1
• Needs systemic immunosuppression managed by dermatology 5

Drug-Induced Severe Cutaneous Reactions (Stevens-Johnson Syndrome/TEN)

• Blistering affecting oropharynx with hemorrhagic crusting of lips, occurring 1-6 weeks after drug initiation 1
• Associated with fever, constitutional symptoms, and potential skin involvement 1
• Most common with antiretrovirals (nevirapine, efavirenz), anticonvulsants, and antibiotics 1
• Requires immediate drug discontinuation and urgent specialist referral 1, 5

Infectious Causes

• Herpes simplex: Painful vesicles and erosions, often with prodromal tingling 5
• Candidal infection: May cause angular cheilitis with cracking at lip corners, especially in immunocompromised or diabetic patients 6, 5
• Bacterial abscess: Rare but presents with severe pain, swelling, fluctuance, fever, and potential airway compromise 7

Traumatic Injury

• History of recent dental work, hard food consumption, or accidental bite 2, 3
• Localized to site of trauma without systemic symptoms 2

Diagnostic Workup Algorithm

First-Line Investigations

• Full blood count: Rule out blood dyscrasias, leukemia, or eosinophilia suggesting drug reaction 1
• Blood glucose: Identify diabetes as risk factor for angina bullosa hemorrhagica or fungal infection 1, 3
• HIV and syphilis serology: If risk factors present or unexplained oral lesions 1

When to Perform Biopsy

• Any blister persisting >2 weeks without clear benign cause requires biopsy 1, 5
• Take perilesional tissue for histology and uninvolved buccal mucosa for direct immunofluorescence if autoimmune disease suspected 1
• Biopsy is contraindicated in acute Stevens-Johnson syndrome; diagnosis is clinical 1

Immediate Management Approach

Universal Supportive Care (All Cases)

• Apply white soft paraffin ointment to lips and affected areas every 2 hours 1, 6, 2, 5
• Clean mouth daily with warm saline mouthwashes 1, 6, 2, 5
• Use benzydamine hydrochloride rinse every 2-4 hours, particularly before eating 1, 6, 5
• For inadequate pain control, apply viscous lidocaine 2% topically 1, 6, 5

Blister-Specific Management

• Pierce intact blisters at base with sterile needle to decompress, leaving roof in situ as biological dressing 5
• Gently apply pressure with sterile gauze to facilitate drainage 5
• Cleanse with antimicrobial solution before and after piercing 5

Infection Prevention

• Use 0.2% chlorhexidine digluconate mouthwash twice daily as antiseptic 1, 2, 5
• For suspected fungal involvement, use nystatin oral suspension or miconazole oral gel 6, 5
• Obtain bacterial cultures if infection suspected and administer appropriate antibiotics 6

Critical Pitfalls to Avoid

• Never use alcohol-containing mouthwashes as they exacerbate pain and delay healing 6, 2, 5
• Do not chronically use petroleum-based products as they promote mucosal dehydration 6, 5
• Do not delay ophthalmology referral if Stevens-Johnson syndrome suspected 5
• Avoid debriding blisters except in specialized burn centers for severe cases 5

When to Escalate Care

• Immediate specialist referral required for: Extensive mucocutaneous involvement suggesting Stevens-Johnson syndrome 1, 5, suspected autoimmune blistering disease requiring immunosuppression 1, 5, or signs of airway compromise 7
• Reevaluate diagnosis if no improvement after 2 weeks of appropriate treatment 6, 5
• Consider superior pathology consultation if initial biopsy shows only nonspecific inflammation 1