What is the management of bullous pemphigoid?

Management of Bullous Pemphigoid

First-Line Treatment: Superpotent Topical Corticosteroids

For extensive bullous pemphigoid, superpotent topical corticosteroids (clobetasol propionate 0.05%) are superior to oral corticosteroids, providing better disease control with significantly lower mortality (76% vs 58% one-year survival) and fewer severe complications (29% vs 54%). 1, 2, 3

Initial Treatment Dosing by Disease Severity

Extensive/Generalized Disease:

• Apply clobetasol propionate 0.05% cream 30-40g daily over the entire body except the face 1, 2
• Use 20g daily if weight <45kg 1, 2
• Apply in one daily application to both normal skin and lesions 1
• If disease control is not achieved within 1-3 weeks, increase to 40g daily 1, 2

Localized/Limited Disease:

• Apply clobetasol propionate 10-20g daily to lesional skin only 1, 2
• For mild disease with few disseminated lesions, use 20g daily over entire body except face 1

Mild Disease (fewer than 10 new blisters per day):

• Apply clobetasol propionate 20g daily 1
• Increase to 40g daily if no control within 1-3 weeks 1

Disease Control Definition and Monitoring

• Disease control = absence of new lesions or healing of established lesions 2
• Assess response after 1-3 weeks of initial treatment 1, 2
• Schedule follow-up every 2 weeks for first 3 months, then monthly for next 3 months, then every 2 months 2
• Monitor for skin atrophy, purpura, and infections as topical steroid side effects 2

Tapering Protocol

After achieving disease control:

• Begin tapering 15 days after disease control is achieved 1, 2
• Reduce dose by 50% every 2 weeks until reaching 10g daily 1
• After 4 months of treatment, reduce to maintenance therapy of 10g once weekly applied to previously affected areas 2
• Continue maintenance for 8 months (total treatment duration 12 months) 2
• Aim to stop treatment 4-12 months after initiation 1

Common pitfall: Do not reduce doses too rapidly or completely suppress all blisters—the occasional urticarial lesion or blister is acceptable and indicates the patient is not being over-treated. 1

Second-Line Treatment: Systemic Corticosteroids

If topical corticosteroids fail or are impractical, use oral prednisone at 0.5-0.75 mg/kg/day—never exceed 0.75 mg/kg/day as higher doses provide no additional benefit but dramatically increase mortality. 1, 2, 4

Systemic Corticosteroid Dosing

For extensive disease:

• Start prednisone 0.5-0.75 mg/kg/day 1, 2
• Doses <0.5 mg/kg are ineffective and not recommended 1
• Doses >0.75 mg/kg (e.g., 1 mg/kg) are associated with higher mortality and increased side-effects compared to lower doses 1, 5

For mild/moderate disease:

• Start prednisone 0.5 mg/kg/day 1
• Alternative: 20-40mg daily depending on severity 1

Critical warning: The most dangerous error is aggressive dose escalation beyond 0.75 mg/kg/day, which confers no therapeutic benefit but dramatically increases mortality risk. 4, 5

Systemic Steroid Tapering

• Begin tapering 15 days after disease control 1
• If no control within 1-3 weeks at 0.5 mg/kg, increase to 0.75 mg/kg 1
• Implement osteoporosis prevention measures from the start of systemic corticosteroid therapy 1, 2

Adjuvant Immunosuppressive Therapy

Consider adding azathioprine if the corticosteroid dose cannot be reduced to an acceptable level, as it allows reduction of steroid dose by approximately 45%. 1, 2, 5

When to Add Adjuvants

• If disease control cannot be achieved at prednisone 0.75 mg/kg/day 4
• If unacceptable corticosteroid side effects develop 1
• To achieve steroid-sparing effect during maintenance 1, 2

Alternative Adjuvant Options

• Mycophenolate mofetil 4
• Methotrexate (particularly if patient has concurrent psoriasis) 1, 4
• Tetracycline (500-2000mg daily) plus nicotinamide for mild-moderate disease 1, 2, 5
• Doxycycline (200-300mg daily) or minocycline (100-200mg daily) plus nicotinamide 2

Tetracycline precautions:

• Avoid tetracycline in renal impairment 2
• Avoid doxycycline/minocycline in hepatic impairment 2
• Discontinue minocycline if hyperpigmentation, pneumonia, or eosinophilia develop 2

Managing Relapse

Relapse is defined as ≥3 new blisters/month, at least one large eczematous/urticarial lesion not healing within 1 week, extension of established lesions, or daily pruritus in a patient who achieved disease control. 1, 4

Relapse Treatment Protocol

For relapse after treatment withdrawal:

• Localized relapse: clobetasol propionate 10g daily applied to previously affected areas 1
• Mild disease relapse: 20g daily 1
• Extensive relapse: 30g daily 1

For relapse during dose reduction:

• Return to the previous dose that successfully controlled disease 4
• Do not exceed prednisone 0.75 mg/kg/day 4
• If no response to re-escalation within 1-3 weeks, add adjuvant therapy (azathioprine, mycophenolate mofetil, tetracycline plus nicotinamide, or methotrexate) 4

Relapse risk factors:

• Anti-BP180 IgG ELISA >27 U/mL indicates increased risk 2, 6
• Positive direct immunofluorescence at treatment discontinuation 2
• Approximately 50% of patients relapse during dose reduction 4

Monitoring During Treatment

Laboratory monitoring:

• Complete blood count, ESR, CRP, creatinine, electrolytes, fasting glucose, liver function tests, serum albumin 4, 6
• Anti-BP180 IgG by ELISA at days 0,60, and 150 to assess disease activity and predict relapse 2, 6

Treatment Discontinuation

• Consider discontinuing after 12 months if symptom-free for at least 1-6 months on minimal therapy 2
• Bullous pemphigoid is self-limiting and usually remits within 5 years 1, 2
• The occasional blister during maintenance is not an indication for increasing treatment 1

Practical Wound Care

• Leave small blisters intact 2
• Puncture and drain larger blisters, leaving the blister roof in place 2