A female breast cancer patient on immunotherapy has mild, localized bullous lesions between the toes without mucosal involvement; how should this be managed?

Management of Localized Bullous Lesions Between Toes in a Breast Cancer Patient on Immunotherapy

For mild, localized bullous lesions between the toes without mucosal involvement in a patient on immunotherapy, continue immunotherapy and initiate very potent topical corticosteroids (clobetasol propionate 0.05% cream) applied twice daily to the affected areas, with dermatology consultation if no improvement within 2 weeks. 1

Initial Assessment and Classification

This presentation is consistent with grade 1-2 immune-related bullous dermatosis, most likely bullous pemphigoid (BP), which can be preceded by or present with localized lesions before developing more widespread disease. 1

• Localized bullous lesions without mucosal involvement and limited body surface area involvement classify this as mild disease (grade 1-2). 1
• Pruritus often precedes or accompanies bullous pemphigoid in immunotherapy patients, even when bullae are not yet prominent. 1
• The absence of mucosal involvement and limited distribution (only between toes) indicates this is not severe Stevens-Johnson syndrome or toxic epidermal necrolysis. 1

Immediate Management Strategy

Continue Immunotherapy

Do not interrupt immunotherapy for grade 1-2 localized skin reactions. 1 The ESMO guidelines explicitly state that mild to moderate skin adverse events do not require treatment interruption, and the clinical benefit of cancer therapy should not be compromised for manageable dermatologic toxicity. 1

Topical Corticosteroid Therapy

Apply clobetasol propionate 0.05% cream (very potent topical steroid) twice daily directly to the bullous lesions and surrounding erythematous areas. 1

• For localized bullous pemphigoid, very potent topical steroids applied to lesional skin alone have Level A evidence for efficacy. 1
• This approach avoids systemic steroid exposure and associated complications (hyperglycemia, hypertension, immunosuppression) that could complicate both cancer treatment and immunotherapy efficacy. 1

Supportive Care Measures

• Apply emollients to surrounding skin to prevent xerosis and secondary fissuring. 1
• Avoid hot water exposure and excessive soap use on feet, which can worsen skin barrier dysfunction. 1
• Consider oral antihistamines (cetirizine 10 mg daily or fexofenadine 180 mg daily) if pruritus is present. 1

Monitoring and Escalation Criteria

Reassessment Timeline

Reassess after 2 weeks of topical therapy. 1 This is the standard timeframe recommended by both ESMO immunotherapy guidelines and British Association of Dermatologists bullous pemphigoid guidelines. 1

Criteria for Dermatology Referral

Refer to dermatology if any of the following occur: 1

• No improvement or worsening after 2 weeks of very potent topical steroids 1
• Spread beyond the interdigital spaces to involve >10% body surface area 1
• Development of mucosal involvement 1
• Progression to grade 3 (>30% body surface area involvement with associated symptoms) 1

Diagnostic Confirmation

If lesions persist or worsen, dermatology should perform: 1

• Punch biopsy for histopathology showing subepidermal blistering with eosinophils 1
• Direct immunofluorescence demonstrating linear C3 and IgG deposits at the basement membrane zone 1
• Serum testing for anti-BP180 and anti-BP230 antibodies 1

When to Escalate Treatment

Grade 2 Progression (10-30% BSA)

If lesions spread but remain grade 2, withhold immunotherapy temporarily and initiate oral prednisolone 0.5-1 mg/kg daily for 3 days, then taper over 1-2 weeks while continuing very potent topical steroids. 1

Grade 3 Progression (>30% BSA with symptoms)

Withhold immunotherapy and initiate intravenous methylprednisolone 0.5-1 mg/kg, converting to oral steroids upon response with taper over 2-4 weeks. 1

Alternative to Systemic Steroids

For patients with contraindications to systemic steroids (diabetes, hypertension, immunosuppression concerns), consider anti-inflammatory antibiotics: 1

• Doxycycline 200 mg daily 1
• This approach has Level D evidence but is widely used and may be safer than systemic steroids in patients with significant comorbidities. 1

Critical Pitfalls to Avoid

Do not discontinue immunotherapy prematurely for localized, mild bullous lesions. 1 The mortality benefit from continued cancer immunotherapy far outweighs the morbidity risk from manageable localized skin toxicity. 1

Do not use systemic corticosteroids as first-line therapy for localized disease. 1 Very potent topical steroids have equivalent efficacy for localized bullous pemphigoid with significantly fewer adverse effects. 1

Do not assume all bullous lesions in immunotherapy patients are benign. 1 While rare, life-threatening conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis can occur, but these typically present with mucosal involvement, skin sloughing >30% BSA, and systemic symptoms—none of which are present in this case. 1

Do not delay dermatology consultation if lesions progress despite appropriate topical therapy. 1 Early specialist involvement allows for diagnostic confirmation and prevents progression to severe disease requiring immunotherapy discontinuation. 1