Bullous Pemphigoid
The most likely diagnosis for a 70-year-old male presenting with a tense bulla on the hand and a negative Nikolsky sign is bullous pemphigoid (BP). 1
Clinical Reasoning
The combination of clinical features strongly points toward BP:
- Age >70 years is a key diagnostic criterion, as BP typically affects elderly patients with a mean age of onset around 80 years 1
- Tense bullae are the hallmark of BP, arising on erythematous or normal-appearing skin, most commonly on the limbs and trunk 1
- Negative Nikolsky sign is characteristic of BP and helps distinguish it from pemphigus vulgaris and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), where the sign is typically positive 1, 2
Key Distinguishing Features
BP differs from conditions with positive Nikolsky sign:
- In SJS/TEN, the Nikolsky sign is positive, with flaccid bullae, extensive mucosal involvement, and constitutional symptoms including fever and malaise 1, 3
- In pemphigus vulgaris, the Nikolsky sign is positive, with flaccid (not tense) bullae and prominent mucosal involvement 3, 4
- In staphylococcal scalded skin syndrome (SSSS), the Nikolsky sign is positive but mucosal involvement is absent, which helps distinguish it from TEN 1, 3
Diagnostic Workup Required
To confirm BP diagnosis, the following tests are essential:
- Direct immunofluorescence (DIF) from perilesional skin (not from the blister itself) showing linear IgG and/or C3 deposits along the dermoepidermal junction—this is the gold standard and essential for diagnosis 1, 5
- Histopathology from an early intact bulla showing subepidermal clefting with eosinophilic infiltrate 1
- Serum ELISA for anti-BP180 and anti-BP230 antibodies, though DIF remains the most critical diagnostic test 1, 5
Clinical Diagnostic Criteria
High specificity (95%) for BP when three of four criteria are present with positive DIF: 1, 6
- Age >70 years
- Absence of atrophic scarring
- Absence of mucosal involvement (or minimal involvement)
- Absence of predominant bullous lesions on neck and head
Important Clinical Pitfalls
Obtain medication history carefully, as BP can be drug-induced by furosemide, spironolactone, neuroleptics, and gliptins (DPP-IV inhibitors), though this is more common in younger patients 1, 7, 8
Biopsy technique matters critically: The DIF specimen must be taken from perilesional skin approximately 1 cm away from a fresh blister, not from the blister itself, to avoid false-negative results 1, 5, 7
Secondary infection risk is significant in BP patients, particularly with MRSA, requiring vigilant monitoring 2