What causes a rash in the mouth with white blood cells present?

White Blood Cells in Oral Rash: Autoimmune Blistering Disease

The most likely cause of white blood cells (specifically IgG antibodies and inflammatory cells) in an oral rash is pemphigus vulgaris (PV), an autoimmune blistering disease where IgG antibodies attack desmosomal proteins, causing painful erosions that typically begin in the mouth. 1

Understanding the Pathophysiology

The "white blood cells" detected in oral rashes with blistering represent:

• IgG autoantibodies targeting desmoglein 3 (the major antigen) and sometimes desmoglein 1, which are desmosomal proteins that hold epithelial cells together 1
• Inflammatory infiltrates including eosinophils and other immune cells that accumulate in response to the autoimmune attack 1
• Complement deposition (C3) on keratinocyte cell surfaces, visible on immunofluorescence testing 1

Clinical Presentation of Pemphigus Vulgaris

Suspect PV in any patient with persistent oral erosions or blisters, particularly when:

• The oral mucosa is the first and sometimes only site involved (occurs in the majority of cases) 1
• Painful erosions affect the buccal mucosa, soft palate, lips, tongue, or gingival margins 1
• Diagnostic delay is common when confined to oral mucosa alone 1
• The disease may extend to skin after an average lag period of 4 months 1
• Peak frequency occurs in the third to sixth decades of life 1

Diagnostic Approach: Gold Standard Testing

Direct immunofluorescence (DIF) remains the gold-standard diagnostic investigation and should be performed on all suspected cases 1:

Biopsy Protocol for Oral Disease

• Take a histology specimen from perilesional mucosa (adjacent to but not directly on the lesion) 1
• Take a DIF sample from uninvolved buccal mucosa (ideally) 1
• DIF sensitivity is 71% in oral biopsies compared to 61% in normal skin 1

Expected Findings

• Histology: Suprabasal acantholysis with blister formation 1
• DIF: Characteristic deposition of IgG and/or complement (C3) on the cell surfaces of epithelial keratinocytes 1
• Indirect immunofluorescence (IIF): Less sensitive than DIF but useful when biopsy is difficult; sensitivity of 85% 1
• ELISA testing: Direct measurement of desmoglein 1 and 3 antibodies in serum; complementary to IIF 1

Critical Prognostic Information

Untreated pemphigus vulgaris has severe mortality implications:

• Average mortality was 75% before corticosteroid introduction in the 1950s 1
• Current mortality ranges from 1-17% for predominantly mucosal PV to 8-42% for mucocutaneous PV 1
• Mucocutaneous PV is more severe, responding slower to treatment and less likely to achieve remission off-treatment 1

Alternative Diagnosis: Bullous Pemphigoid

If the patient is elderly (>70 years) with oral involvement, consider bullous pemphigoid (BP), though oral lesions are less common 1:

• BP shows linear deposits of IgG and/or C3 at the basement membrane zone on DIF (different pattern than PV) 1
• Oral lesions consist of small blisters or erosions mainly on palatal mucosa 1
• Subepidermal cleft on histology with mixed dermal inflammatory infiltrate containing numerous eosinophils 1

Common Pitfalls to Avoid

• Do not delay biopsy waiting for skin lesions to appear; oral-only PV is common and diagnostic delay worsens outcomes 1
• Transport medium matters: Use saline for up to 24 hours (optimal) or Michel's medium for longer transportation times; avoid liquid nitrogen due to practical disadvantages 1
• Do not rely on histology alone: Suprabasal acantholysis is suggestive but must be confirmed by characteristic IgG/complement deposition on DIF 1
• Distinguish from other causes: The pattern of immunoglobulin deposition differentiates PV (intercellular) from BP (linear basement membrane) and other blistering diseases 1