Differential Diagnoses in Dermatology

Key Diagnostic Considerations

Research recent drug intake over the past 1-6 months, particularly diuretics, psycholeptic drugs, and checkpoint inhibitors, as these are known triggers for bullous pemphigoid, according to the British Journal of Dermatology 1
Checkpoint inhibitor-associated bullous pemphigoid specifically presents with pruritus that can precede or be the sole manifestation, followed by urticarial plaques before frank bullae develop, as reported in the Annals of Oncology 2
The histopathologic findings of mild superficial perivascular lymphocytic infiltration and mild papillary edema are consistent with early or non-bullous bullous pemphigoid, where findings may be nonspecific, as noted in the British Journal of Dermatology 1
Direct immunofluorescence (DIF) from perilesional skin is essential, as linear IgG and/or C3 deposits along the dermoepidermal junction would confirm bullous pemphigoid even without bullae, according to the British Journal of Dermatology 1, 3
Erythema multiforme can present with urticarial plaques and target lesions, though typically has more prominent mucosal involvement, as described in the British Journal of Dermatology 4

Obtain DIF from perilesional skin, which is the most critical test and essential for diagnosis of bullous pemphigoid, as recommended by the British Journal of Dermatology 1, 3
Order serum ELISA for anti-BP180 and anti-BP230 antibodies, as anti-BP180 ELISA is more sensitive and can detect disease even with negative indirect immunofluorescence, according to the British Journal of Dermatology 3
Complete medication history review, specifically asking about drugs started 1-6 months before symptom onset, as suggested by the British Journal of Dermatology and Annals of Oncology 1, 2

Apply validated bullous pemphigoid clinical criteria, which include age, absence of atrophic scars, absence of mucosal involvement, and absence of predominant bullous lesions on neck/head, with positive DIF, to make a diagnosis with high specificity and sensitivity, as noted in the British Journal of Dermatology 1

The dermal infiltrate is composed of eosinophils and/or neutrophils, though this may be subtle, in non-bullous bullous pemphigoid patients 5
Marginalization of eosinophils along the dermoepidermal junction is present when eosinophils are found in non-bullous bullous pemphigoid patients 5
Absence of subepidermal bullae containing eosinophils and/or neutrophils is a key distinction from classic bullous pemphigoid 5

Sometimes IgA and IgE deposits with similar linear pattern are found along the dermoepidermal junction in non-bullous bullous pemphigoid patients 5
N-serrated pattern of deposition is present when IgG and/or C3 deposits are found along the dermoepidermal junction in non-bullous bullous pemphigoid patients 5
Positive DIF is essential for diagnosis of bullous pemphigoid, including non-bullous variants, according to the British Journal of Dermatology guidelines 5

Do not rely on histopathology alone—always obtain DIF from perilesional skin when bullous pemphigoid is suspected in elderly patients with refractory pruritus, as recommended by the British Journal of Dermatology 5
Obtain DIF from perilesional skin, as this is the single most important diagnostic test for non-bullous bullous pemphigoid, according to the British Journal of Dermatology guidelines 5
Indirect immunofluorescence on salt-split skin should be performed if ELISA is unavailable, as recommended by the British Journal of Dermatology 5