How should bullous pemphigoid be treated in an elderly patient, with options for limited versus extensive disease and steroid‑sparing agents?

Treatment of Bullous Pemphigoid

Superpotent topical corticosteroids (clobetasol propionate 0.05% cream) are the first-line treatment for bullous pemphigoid in elderly patients, providing superior disease control with significantly lower one-year mortality compared to systemic corticosteroids. 1, 2, 3

Initial Treatment Strategy Based on Disease Extent

Limited/Localized Disease (< 10% BSA)

• Apply clobetasol propionate 0.05% cream 10–20 g daily directly to lesional skin only, which achieves complete healing in all patients within 4–17 days. 1, 2, 4
• If disease control is not achieved within 1–3 weeks, escalate to 40 g daily. 1, 2

Mild Disease with Widespread Distribution

• Apply clobetasol propionate 20 g daily over the entire body except the face. 1, 2
• For patients weighing < 45 kg, reduce the daily amount to 20 g. 1

Extensive/Moderate-to-Severe Disease

• Apply clobetasol propionate 30–40 g daily to the entire body surface excluding the face in two divided applications. 1, 2, 3
• This regimen achieves disease control in 99% of patients by day 21, compared to 91% with oral prednisone. 3, 5
• One-year mortality is 26.5% with topical clobetasol versus 36.3% with oral prednisone in extensive disease. 3, 5
• In patients aged > 80 years, topical clobetasol achieves a 55% complete response rate with minimal adverse effects. 1, 6

Definition of Disease Control and When to Begin Tapering

• Disease control is defined as cessation of new lesions and pruritic symptoms together with initiation of healing of existing lesions, typically achieved within 1–3 weeks. 1, 2
• Begin tapering 15 days after disease control is established—earlier reduction has not been validated. 1, 2

Structured Tapering Protocol

• Month 1: Daily application 1
• Month 2: Every 2 days 1
• Month 3: Twice per week 1
• Month 4 onward: Once per week 1
• After 4 months, transition to maintenance regimen of 10 g applied once weekly to previously affected areas for a total treatment duration of 12 months. 1, 2

Monitoring for Adverse Effects of Topical Therapy

• Watch for skin atrophy (14.9%), purpura (5.4%), and secondary infections—these occur far less frequently than systemic complications from oral steroids. 1, 7
• Severe complications occur in 29% of patients on topical clobetasol versus 54% on oral prednisone. 3, 5

Systemic Corticosteroid Therapy (Second-Line)

When to Use Systemic Steroids

• Reserve oral corticosteroids for patients who cannot apply topical therapy (e.g., severe functional impairment, lack of caregiver assistance) or when topical therapy fails. 1, 6

Dosing for Systemic Prednisone/Prednisolone

• Moderate disease: 0.3–0.5 mg/kg/day 1, 2
• Severe/widespread disease: 0.75–1.0 mg/kg/day, which achieves disease control in 60–90% of cases within 1–4 weeks 1
• Critical warning: Doses > 0.75 mg/kg/day (≈ 52.5 mg/day for a 70-kg adult) do not improve outcomes and are associated with substantially increased mortality in elderly patients. 1

Systemic Steroid Tapering

• Once new lesions cease (typically within 4 weeks), reduce daily dose by one-third or one-quarter every two weeks until 15 mg/day is reached. 1
• Continue tapering by 2.5 mg decrements every two weeks until 10 mg/day. 1
• After reaching 10 mg/day, decrease by 1 mg each month until discontinuation. 1
• Approximately 50% of patients relapse during dose reduction; the dose just before relapse represents the minimal effective dose for that individual. 1

Osteoporosis Prophylaxis

• Immediately initiate calcium, vitamin D, and bisphosphonate therapy at the start of systemic corticosteroids in elderly patients with existing osteoporosis. 1, 2

Steroid-Sparing Agents

Doxycycline (Preferred Alternative to Systemic Steroids)

• Doxycycline 200 mg daily (with or without nicotinamide 500–2500 mg daily) is a safer alternative to systemic corticosteroids, producing a 73.8% response rate at six weeks. 1, 2, 5
• Doxycycline reduces one-year mortality to 2.4% versus 9.7% with prednisolone (NNTB = 14). 5
• Doxycycline improves quality of life by 1.8 points on the Dermatology Life Quality Index compared to prednisolone. 5
• Caution: Avoid doxycycline in hepatic impairment; avoid tetracycline in renal impairment. 1

Azathioprine (Adjunctive Therapy)

• Adding azathioprine (up to 2.5 mg/kg daily) to systemic corticosteroids does not improve overall disease-control rates but reduces cumulative steroid exposure by approximately 45%. 1, 8
• Azathioprine achieves remission in 100% of patients with a median time of 28.6 days when used as adjunctive therapy. 8
• Check thiopurine methyltransferase activity before starting to minimize myelosuppression risk. 8
• Monitor complete blood counts and liver function regularly. 8

Mycophenolate Mofetil (Alternative to Azathioprine)

• Mycophenolate mofetil 0.5–1 g twice daily achieves remission in 100% of patients with a median time of 42 days. 8
• Mycophenolate has less hepatotoxicity but more infections compared to azathioprine. 8
• Prefer mycophenolate when hepatotoxicity is a concern; prefer azathioprine when cost or infection risk are priorities. 8

Methotrexate (Third-Line Option)

• Methotrexate 5–15 mg weekly (with folic acid 5 mg on non-methotrexate days) is a third-line steroid-sparing option when azathioprine or mycophenolate fail or cause intolerable side effects. 1, 8
• In pooled prospective studies, 76% of patients achieved remission when methotrexate was combined with topical steroids. 1
• The largest retrospective cohort showed 43% reached remission at 24 months on methotrexate monotherapy (median dose 5 mg/week), with a median time to remission of 11 months. 1
• Low weekly doses are sufficient in older adults with reduced renal function because methotrexate is renally excreted. 1
• Monitor for myelosuppression, hepatotoxicity, and methotrexate-induced pneumonitis. 1
• Critical warning: Methotrexate must not be used as first-line therapy and has slower response than systemic corticosteroids. 1

Refractory Disease

Rituximab (Most Studied Biologic)

• Rituximab 375 mg/m² weekly for 4 weeks is the most studied biologic for refractory bullous pemphigoid, achieving satisfactory response in 78% and complete clearance in 55% of recalcitrant cases. 2, 8
• Caution: Rituximab is associated with a relatively high mortality rate (29%) in patients aged > 80 years, warranting meticulous patient selection. 6
• Consider rituximab only when all standard immunomodulators have failed. 8

Intravenous Immunoglobulin (IVIg)

• IVIg can be considered for cases unresponsive to all standard therapies, and may be used as a steroid-sparing option in severe cases. 9, 2

Plasma Exchange

• Evidence for plasma exchange is mixed: one study showed better disease control when combined with prednisone, while another found no significant difference and a trend toward increased adverse events. 1

Monitoring Schedule

• First 3 months: Every 2 weeks 2
• Months 4–6: Monthly 2
• Thereafter: Every 2 months 2
• Baseline and regular monitoring: Complete blood count, liver function tests, glucose, renal function, blood pressure 2
• Anti-BP180 IgG by ELISA at days 0,60, and 150; values > 27 U/mL indicate increased relapse risk. 2
• Serial clinical photography to track disease progression or improvement. 9

Treatment Discontinuation

• Consider discontinuing treatment after 12 months if the patient has been symptom-free for at least 1–6 months on minimal therapy. 1
• Positive direct immunofluorescence or BP180 ELISA > 27 U/mL indicates increased risk of relapse. 1, 2
• Bullous pemphigoid is a self-limiting disease that usually remits within 5 years. 1

Local Wound Care

• Apply plain petrolatum ointment and bandages over any open erosions. 9
• Small blisters should be left intact; larger blisters should be punctured and drained, leaving the blister roof in place. 1

Common Pitfalls to Avoid

• Do not start with high-dose systemic corticosteroids (> 0.75 mg/kg/day) in elderly patients—this increases mortality without improving outcomes. 1, 3
• Do not use azathioprine or other immunomodulators as first-line therapy—there is insufficient evidence that adding them to corticosteroids improves initial disease control. 8
• Do not overlook osteoporosis prophylaxis when initiating systemic corticosteroids in elderly patients. 1, 2
• Do not use methotrexate as first-line therapy—it is slower-acting and has weaker evidence than topical or systemic corticosteroids. 1