What are the pathological findings of non-bullous pemphigoid and how does it differ from bullous pemphigoid?

Pathological Findings of Non-Bullous Pemphigoid and Differences from Bullous Pemphigoid

Non-bullous pemphigoid (NBP) is a distinct variant of bullous pemphigoid (BP) characterized by the absence of blisters but with identical immunopathological findings, including linear deposits of IgG and/or C3 along the dermoepidermal junction. 1, 2

Pathological Findings of Non-Bullous Pemphigoid

Histopathology

• Light microscopy findings:
  • Moderate eosinophilic infiltrate partly arranged along the basement membrane zone 3
  • Eosinophils may focally invade the epidermis 3
  • Generally nonspecific findings compared to bullous form 2, 4
  • No subepidermal clefting (unlike bullous pemphigoid) 2
  • Dermal infiltrate of eosinophils and/or neutrophils 1

Immunopathology

• Direct immunofluorescence (DIF):

  • Linear deposits of IgG and/or C3 along the dermoepidermal junction 1
  • Positive in approximately 93% of cases 4
  • Biopsy must be taken from perilesional skin (1 cm away from lesion) 1, 5
  • Sometimes IgA and IgE with similar pattern 1

• Indirect immunofluorescence (IIF):

  • Positive in about 90% of cases 4
  • Best performed on salt-split skin 1
  • IgG autoantibodies bind to the epidermal side of the split 1

• Immunoelectron microscopy:

  • Deposits localized within the lamina lucida and over hemidesmosomal plaques 3

• Serological findings:

  • Circulating autoantibodies against BP230 (230 kD bullous pemphigoid antigen) 3
  • Anti-BP180 (collagen XVII) antibodies may be present 1, 5
  • Elevated IgE levels (4.1 times higher than in bullous form) 6
  • Significantly increased blood eosinophil count 6

Differences Between Non-Bullous and Bullous Pemphigoid

Clinical Presentation

• Non-bullous pemphigoid:

  • No blisters or vesicles 3, 2
  • Presents with pruritic papules/nodules (37%) or pruritus without primary skin lesions (22%) 2
  • Erythematous, urticarial plaques (52.3%) 4
  • Excoriations, prurigo-like lesions, eczematous lesions 1, 5
  • May precede bullous form by weeks, months, or years 1
  • Only 9.8-23% of patients develop blisters during follow-up 2, 6

• Bullous pemphigoid:

  • Tense blisters on erythematous or normal-looking skin 1
  • Widespread or localized bullae 1
  • Oral mucosal involvement in 10-30% of cases 1

Histopathology

• Non-bullous pemphigoid:

  • No subepidermal clefting 2
  • Nonspecific findings in most cases 2, 4

• Bullous pemphigoid:

  • Subepidermal clefting with inflammatory infiltrate 1
  • Dermal infiltrate predominantly of eosinophils 1

Diagnostic Challenges

• Non-bullous pemphigoid:

  • Mean diagnostic delay of 22.6-29 months 2, 4
  • Mimics other pruritic skin diseases 4
  • Requires high index of suspicion in elderly patients with refractory pruritus 5

• Bullous pemphigoid:

  • More readily diagnosed due to characteristic blisters 1

Laboratory Markers

• Non-bullous pemphigoid:
  • Higher IgE levels 6
  • Higher blood eosinophil count 6
  • Positive IIF and BP180 immunoblot associated with higher risk of developing blisters 2

Clinical Implications

• Both forms affect predominantly elderly patients (>70 years) 1, 5
• Both have similar mortality rates (8.6-fold increased all-cause mortality risk in NBP) 2
• Both respond to similar treatments, though treatment intensity may differ 5
• Both are associated with neurological conditions such as dementia, Parkinson's disease, and cerebrovascular disease 5

Diagnostic Algorithm for Suspected Non-Bullous Pemphigoid

1. Consider in elderly patients with persistent unexplained pruritus, especially with urticarial or eczematous lesions 5, 4
2. Perform skin biopsy for histopathology (may show nonspecific findings) 2
3. Obtain perilesional skin biopsy for DIF (essential for diagnosis) 1
4. Perform serum testing with IIF on salt-split skin and ELISA for anti-BP180 and anti-BP230 antibodies 1, 5
5. Monitor for potential development of blisters, especially in patients with positive IIF and BP180 immunoblot 2

Understanding these differences is crucial for early diagnosis and appropriate management of non-bullous pemphigoid, which is often underdiagnosed due to its atypical presentation.