What is the initial workup for a patient suspected of having pemphigus vulgaris?

Initial Workup for Pemphigus Vulgaris

The initial workup for suspected pemphigus vulgaris must include skin/mucosal biopsies for both routine histopathology and direct immunofluorescence (DIF), along with serum testing for autoantibodies. 1

Diagnostic Biopsies

Skin/Mucosal Biopsy Collection

• Lesional biopsy for histopathology:

  • Take from a fresh, intact blister or erosion
  • Look for suprabasal acantholysis and intraepithelial blister formation 1

• Perilesional biopsy for DIF:

  • Take from clinically normal-appearing skin/mucosa approximately 1 cm away from lesion 1, 2
  • For oral pemphigus, buccal mucosa is the optimal site 2
  • Never take DIF biopsy from lesional skin as it reduces diagnostic accuracy 2

Biopsy Transport

• Transport medium for DIF:
  • Normal saline (0.9% NaCl) is optimal for transport times ≤24 hours 2
  • Michel's medium preferred for longer transportation times 1
  • Saline provides superior results by washing away non-specific IgG, reducing background interference 2

Serological Testing

• Indirect immunofluorescence (IIF):

  • Use both mucosal substrate (monkey esophagus) and skin substrate for optimal detection 1
  • Mucosal substrates better detect desmoglein 3 antibodies
  • Skin substrates better detect desmoglein 1 antibodies 1

• Enzyme-linked immunosorbent assay (ELISA):

  • Direct measurement of anti-desmoglein 1 and 3 antibodies
  • More sensitive and specific than IIF 1
  • Helpful for disease monitoring 1

Additional Baseline Investigations

Before initiating treatment, obtain the following 1:

• Laboratory tests:

  • Complete blood count and differential
  • Renal function (urea and electrolytes)
  • Liver function tests
  • Fasting glucose and HbA1c
  • Fasting lipids
  • Antinuclear antibody (to rule out pemphigus erythematosus)
  • Pregnancy test in women of childbearing age

• Other assessments:

  • Blood pressure measurement
  • Weight
  • Height (in children)
  • Consider bone density scan if systemic corticosteroid therapy is planned
  • Consider ocular examination (for ocular tension and cataract) if long-term systemic corticosteroid therapy is planned

Special Considerations

• If oral pemphigus is suspected:

  • Intraoral biopsy is optimal but DIF on skin biopsy may suffice
  • DIF sensitivity is 71-89% in oral biopsies versus 61-85% for normal skin in patients with oral PV 1

• If biopsy is difficult (children, uncooperative adults):

  • IIF or ELISA may be helpful as alternative diagnostic methods 1

• Pre-treatment screening if immunosuppression is planned:

  • Serology for hepatitis B, hepatitis C, and HIV
  • Consider tuberculosis screening
  • Consider appropriate vaccinations before immunosuppression 1

Common Pitfalls to Avoid

1. Improper biopsy site selection: Taking DIF from lesional rather than perilesional tissue significantly reduces diagnostic accuracy 2

2. Delayed transport of DIF specimens: Diagnostic accuracy decreases with increased transport time, especially in saline medium 2

3. Using only one diagnostic method: Relying solely on histopathology, DIF, or serology may lead to missed diagnoses; combining methods increases diagnostic accuracy 1

4. Failure to consider drug-induced pemphigus: Always take a thorough drug history as certain medications can trigger pemphigus that mimics idiopathic disease 1

5. Inadequate baseline investigations: Failing to obtain comprehensive baseline tests before initiating treatment may lead to complications during therapy 1