In an 85‑year‑old man with diabetes presenting with a one‑week pruritic maculopapular rash that began on the upper extremities and spread to the lower extremities with occasional small blisters, what is the most likely diagnosis and recommended management?

Bullous Pemphigoid: Most Likely Diagnosis

This 85-year-old diabetic man with a one-week pruritic maculopapular rash progressing from upper to lower extremities with occasional small blisters most likely has bullous pemphigoid (BP), and requires immediate skin biopsy with direct immunofluorescence for confirmation followed by initiation of potent topical corticosteroids. 1

Clinical Presentation Strongly Suggests Bullous Pemphigoid

The clinical picture is classic for BP in several key ways:

• Age >70 years is one of the validated clinical criteria for BP diagnosis, with this disease typically affecting elderly patients 1, 2
• Severe pruritus preceding or accompanying blistering is characteristic, often presenting initially as itchy excoriated, eczematous, or urticarial lesions that persist for weeks before frank bullae develop 1, 2, 3
• Progressive spread from upper to lower extremities with symmetric distribution is typical, particularly affecting flexural surfaces of limbs 1
• Diabetes mellitus is a recognized association, particularly in patients on DPP-4 inhibitors (gliptins), though BP occurs in diabetics regardless of medication use 4

The "occasional small blisters" described represent the transition from the non-bullous prodromal phase to the bullous stage, which can take weeks to months to fully develop 5, 3.

Immediate Diagnostic Workup Required

Three diagnostic steps must be completed urgently:

• Skin biopsy for histopathology: Take specimen from early bullae arising on erythematous skin, placed in formalin, looking for subepidermal bullae with eosinophils and/or neutrophils 1
• Direct immunofluorescence (DIF): This is the most critical test—obtain perilesional skin biopsy looking for linear IgG and/or C3 deposits along the dermoepidermal junction 1
• Serum anti-BP180/BP230 ELISA: Detects circulating autoantibodies against BP180 (most common) or BP230 1, 2

The diagnosis is confirmed when clinical features are combined with compatible histopathology and positive DIF findings 1.

Critical Differential Considerations

While BP is most likely, two important differentials must be excluded:

• Drug-induced BP: Review all medications from the past 1-6 months, particularly diuretics, psycholeptic drugs (phenothiazines), and DPP-4 inhibitors if diabetic 1, 4
• Pruritus as sole presenting feature: In elderly patients, pruritus alone can rarely be the presenting feature of BP before any visible rash develops, requiring high index of suspicion 1

The diabetes-related foot infection guidelines 1 are not relevant here as this patient has no foot wounds or ulcers described.

First-Line Treatment Algorithm

Initiate treatment immediately upon clinical suspicion, do not wait for biopsy results:

For Limited Disease (<30% Body Surface Area):

• Potent topical corticosteroids (e.g., clobetasol propionate 0.05% cream/ointment) applied to all affected areas once or twice daily 1, 6
• Maximum duration 2 consecutive weeks, not exceeding 50g per week due to HPA axis suppression risk 6
• This has emerged as effective and safe first-line treatment for BP 2

For Extensive Disease (>30% BSA) or Rapid Progression:

• Systemic corticosteroids (typically oral prednisone 0.5-0.75 mg/kg/day) combined with topical corticosteroids 1
• Consider adding doxycycline 100mg twice daily as steroid-sparing agent 5
• Referral to dermatologist familiar with BP is mandatory 1

Supportive Care:

• Oral antihistamines for pruritus control 1
• Emollients to maintain skin barrier 1
• Avoid sedating antihistamines in this elderly patient due to fall risk 1

Critical Pitfalls to Avoid

• Do not dismiss as simple drug reaction or eczema without pursuing definitive diagnosis—BP has significant morbidity and mortality in elderly patients 1, 2
• Do not delay biopsy with DIF—this is essential for diagnosis and cannot be replaced by clinical assessment alone 1, 3
• Do not use topical anti-acne medications as these worsen barrier dysfunction 7
• Do not continue suspected causative drugs (particularly DPP-4 inhibitors if present) without dermatology consultation 4

Prognosis and Follow-up

• BP is usually a chronic disease with spontaneous exacerbations and remissions, accompanied by significant morbidity 2
• Neurological comorbidities (dementia, Parkinson's disease, cerebrovascular disease) are independent risk factors and should be assessed 2, 4
• Once diagnosis is confirmed and treatment initiated, close monitoring every 1-2 weeks is required to assess response and adjust therapy 1
• Most patients show improvement after treatment initiation, but long-term maintenance therapy feasibility remains controversial 2