How should I manage a 49-year-old woman on breast cancer immunotherapy who presents with clear‑fluid bullae on her foot after a pedicure, presumed allergic contact dermatitis, in an urgent‑care setting?

Management of Clear Fluid-Filled Blisters on Foot After Pedicure in Patient on Breast Cancer Immunotherapy

This presentation requires urgent consideration of immunotherapy-induced bullous dermatosis rather than simple allergic contact dermatitis, and systemic corticosteroid injection is contraindicated—instead, initiate high-potency topical corticosteroid therapy with close dermatology follow-up and consider holding immunotherapy pending definitive diagnosis. 1

Critical Differential Diagnosis

This clinical scenario demands immediate recognition that bullous eruptions occur in approximately 1% of patients on anti-PD-1/PD-L1 immunotherapy and represent potentially serious immune-related adverse events (irAEs), not simple allergic reactions. 2 The timing after a pedicure may be coincidental rather than causative, as immunotherapy-induced bullous dermatoses can develop weeks to months after treatment initiation and may be triggered by minor trauma or irritation. 1

Key Distinguishing Features to Assess:

• Distribution pattern: Immunotherapy-induced bullous pemphigoid typically presents with widespread involvement beyond the trauma site, whereas true allergic contact dermatitis from pedicure products would be localized to areas of direct contact (dorsal foot, between toes). 1
• Mucosal involvement: Check for oral erosions or conjunctival involvement, which would indicate more severe bullous disease requiring urgent intervention. 1
• Systemic symptoms: Fever, widespread rash, or skin pain would suggest severe cutaneous adverse reactions (SCARs) requiring immediate immunotherapy discontinuation. 1

Why Systemic Steroid Injection Is Inappropriate

Intramuscular or systemic corticosteroid injection is not the standard approach for localized bullous eruptions and carries unnecessary systemic immunosuppression risk in a cancer patient. 1 The ASCO guidelines for immune-related adverse events recommend graded management based on severity, not empiric systemic steroids for all presentations. 1

Recommended Urgent Care Management Algorithm

Immediate Actions:

1. Apply high-potency topical corticosteroid: Initiate clobetasol propionate 0.05% ointment twice daily to affected areas, which is the appropriate first-line therapy for localized bullous eruptions. 3, 4 This provides potent anti-inflammatory effect without systemic immunosuppression. 3

2. Oral antihistamine for symptom control: Diphenhydramine (Benadryl) 25-50 mg every 6 hours as needed is appropriate for pruritus management but will not treat the underlying process. 1

3. Protect bullae from rupture: Apply non-adherent dressings to prevent secondary infection and avoid debridement, as overdebridement makes underlying skin susceptible to increased blistering and tenderness. 5

4. Contact oncology team immediately: The patient's oncologist must be notified same-day, as immunotherapy-induced bullous disorders frequently result in interruption of immune therapy (occurred in 8 of 9 patients in one series). 2

Critical Assessment Before Discharge:

• Body surface area involvement: If bullae extend beyond the foot or involve >10% body surface area, this constitutes grade 2-3 toxicity requiring dermatology consultation within 24-48 hours. 1
• Rule out infection: If erythema, warmth, purulent drainage, or fever are present, obtain bacterial culture and initiate empiric antibiotics (cephalexin 500 mg four times daily), as secondary infection is a common complication. 6

Definitive Diagnostic Plan

Arrange urgent dermatology referral within 3-5 days for:

• Skin biopsy with direct immunofluorescence (DIF): This is essential to distinguish immunotherapy-induced bullous pemphigoid (linear IgG and C3 at dermal-epidermal junction) from allergic contact dermatitis (negative DIF with spongiotic dermatitis on histology). 4, 2
• Serum studies: Anti-BP180 and anti-BP230 antibodies should be checked if bullous pemphigoid is suspected. 4
• Patch testing consideration: If allergic contact dermatitis remains in the differential after excluding immunotherapy-related causes, patch testing can be performed 3 months after finishing systemic agents to identify specific allergens from pedicure products. 1

Management Based on Confirmed Diagnosis

If Immunotherapy-Induced Bullous Pemphigoid (Most Likely):

• Continue clobetasol 0.05% ointment twice daily to affected areas. 4
• Add oral doxycycline 100 mg twice daily with niacinamide 500 mg three times daily as steroid-sparing therapy—this regimen has enabled successful continuation of immunotherapy in documented cases. 4
• Hold immunotherapy temporarily until bullae are controlled, then consider resumption under close monitoring. 4, 2
• Escalate to systemic corticosteroids only if widespread: Prednisone 0.5-1 mg/kg/day for grade 3-4 toxicity with extensive involvement. 1

If True Allergic Contact Dermatitis (Less Likely Given Context):

• Continue clobetasol 0.05% ointment twice daily for 2 weeks. 6
• Identify and avoid specific allergen: Common pedicure-related allergens include acrylates (nail products), fragrances, preservatives (formaldehyde), and rubber chemicals. 1
• No interruption of immunotherapy required. 1

Critical Pitfalls to Avoid

• Never dismiss bullous eruptions in immunotherapy patients as "simple allergic reactions": Approximately 1-5% of patients on anti-PD-L1 agents develop bullous dermatoses, with potentially higher risk than anti-PD-1 agents alone. 4, 2
• Avoid systemic corticosteroid injection without confirmed diagnosis: This provides inappropriate systemic immunosuppression and may mask the true severity of an immune-related adverse event. 1
• Do not continue immunotherapy without dermatology evaluation: Eight of nine patients with immunotherapy-induced bullous disorders required treatment interruption, and failure to recognize this can lead to progressive, potentially life-threatening disease. 2
• Recognize that topical corticosteroid allergy is possible: A small subset of patients develop allergic contact dermatitis to topical corticosteroids themselves, which would manifest as worsening rather than improvement—this should be suspected if no response after 1 week. 1

Follow-Up Timeline

• Reassess in 48-72 hours: If bullae are spreading, developing systemic symptoms, or not improving with topical therapy, urgent dermatology consultation is mandatory. 1
• Dermatology appointment within 3-5 days for biopsy and definitive diagnosis. 1, 2
• Oncology coordination: Document communication with oncology team regarding potential immunotherapy interruption. 2