What is the treatment for erosive-bullous eruptions?

Treatment of Erosive-Bullous Eruptions

For extensive erosive-bullous eruptions, initiate high-potency topical clobetasol propionate 0.05% cream at 30-40 g per day applied over the entire body (sparing the face) as first-line therapy, which has Level 1 evidence for efficacy and superior outcomes compared to systemic corticosteroids alone. 1

Initial Assessment and Diagnosis

Before initiating treatment, confirm the diagnosis through:

• Direct immunofluorescence (DIF) from perilesional skin showing linear IgG and/or C3 deposits along the dermoepidermal junction, which is the most critical diagnostic test 2
• Skin biopsy demonstrating subepidermal blistering with eosinophils and/or neutrophils 1
• Serum ELISA for anti-BP180 antibodies (first choice) or anti-BP230 antibodies if negative 1
• Medication review for drugs initiated 1-6 months prior, particularly diuretics, psycholeptics, checkpoint inhibitors, ACE inhibitors, and DPP-4 inhibitors 1, 3, 4

Treatment Algorithm by Disease Severity

Localized Disease (< 10% Body Surface Area)

Apply clobetasol propionate 0.05% cream twice daily to affected areas only 1

• Continue daily application until disease control is achieved (when new lesions cease and established lesions begin healing) 1
• Begin tapering 15 days after disease control: every other day in month 2, twice weekly in month 3, once weekly starting month 4 1
• If inadequate response within 1-3 weeks, increase application area or frequency 1

Extensive Disease (≥ 10% Body Surface Area or > 10 New Blisters Daily)

Apply clobetasol propionate 0.05% cream 30-40 g per day (20 g if weight < 45 kg) over entire body including normal skin, blisters, and erosions, sparing only the face 1

• This approach has Level 1 validated evidence and is superior to systemic corticosteroids alone 1
• Apply twice daily initially 1
• Begin tapering 15 days after disease control using the same schedule as localized disease 1

Grade 2-3 Bullous Eruptions (Immune Checkpoint Inhibitor-Related)

Hold checkpoint inhibitor therapy immediately and initiate prednisone 0.5-1 mg/kg/day with taper over at least 4 weeks 1

• Apply high-potency topical steroids (clobetasol or betamethasone) to affected areas 1
• Provide local wound care with plain petrolatum ointment and bandages over erosions 1
• Consult dermatology for steroid-sparing options and to determine appropriateness of resuming checkpoint inhibitor 1
• Monitor closely every 3 days for progression 1

Grade 4 Severe Disease (> 30% BSA with Fluid/Electrolyte Abnormalities)

Admit patient immediately and administer IV methylprednisolone 1-2 mg/kg/day 1

• Permanently discontinue checkpoint inhibitor if this is the etiology 1
• Convert to oral steroids when appropriate, tapering over at least 4 weeks 1
• Consider steroid-sparing options (IVIG, rituximab) to avoid long-term systemic steroid use 1

Critical Management Principles

Systemic Corticosteroid Dosing

Avoid oral prednisone doses > 0.75 mg/kg/day, as higher doses provide no additional benefit and significantly increase mortality 3

• For patients requiring systemic therapy, start prednisone at 0.5 mg/kg/day 3
• Consider adding azathioprine as adjunctive therapy to allow approximately 45% reduction in steroid dose 3
• Prednisone is FDA-approved for pemphigus and bullous dermatitis herpetiformis 5

Wound Care and Supportive Measures

• Leave intact blisters undisturbed when possible to prevent secondary infection 1
• Pierce large or troublesome blisters with sterile needle, releasing fluid but leaving blister roof intact 1
• Apply antiseptics (potassium permanganate baths or antiseptic bath oils) for extensive erosions to prevent infection 1
• Cover painful eroded areas with low-adhesion dressings (Mepitel or Atrauман) held with soft elasticated viscose 1

Drug Withdrawal Strategy

Immediately discontinue any potentially causative medications identified in the 1-6 month period before symptom onset 1, 3

• Priority drugs to discontinue: checkpoint inhibitors, diuretics (especially spironolactone), neuroleptics, ACE inhibitors, PPIs, DPP-4 inhibitors 3, 4
• Drug-induced bullous pemphigoid may not resolve with drug withdrawal alone and often requires immunosuppressive treatment 4

Steroid-Sparing Options for Refractory Cases

When topical clobetasol and/or systemic corticosteroids fail or are contraindicated:

• IVIG can be used as alternative to long-term systemic steroids, particularly in bullous pemphigoid 1
• Rituximab has shown efficacy in case series, allowing gradual withdrawal of other immunosuppressants, though serious adverse events including fatal infections have occurred 1
• Tetracycline antibiotics can be combined with corticosteroids for management 4

Common Pitfalls to Avoid

• Do not delay DIF testing – it is essential even when clinical diagnosis seems obvious, as other conditions can mimic bullous pemphigoid 2
• Do not use oral challenge testing to confirm drug causality due to risk of severe exacerbation or generalization; patch testing is preferred 6
• Do not continue checkpoint inhibitors in patients with grade ≥2 bullous eruptions without dermatology consultation 1
• Do not assume drug-induced cases will self-resolve after drug withdrawal – most require active immunosuppressive treatment 4
• Do not overlook mucosal involvement – extensive mucosal disease may indicate Stevens-Johnson syndrome or toxic epidermal necrolysis rather than bullous pemphigoid and requires different management 1, 6

Monitoring During Treatment

• Assess for disease control every 3 days initially, defined as cessation of new lesions and pruritus with healing of established lesions 1
• Monitor for HPA axis suppression in patients using > 2 g/day of clobetasol over large surface areas through urinary free cortisol and ACTH stimulation tests 7
• Evaluate for corticosteroid side effects including hyperglycemia, fluid retention, and infection risk, particularly in elderly patients with comorbidities 1, 4