KEY POINTS
- A 50-year-old woman with stage IIIB triple-negative breast cancer received neoadjuvant KEYNOTE-522 chemoimmunotherapy, followed by mastectomy and maintenance pembrolizumab 200 mg every 3 weeks. Residual disease was ypT1a ypN1a(sn), with one of nine sampled nodes involved.
- Postmastectomy radiotherapy prescribed 50 Gy in 25 fractions to the reconstructed right breast and regional nodes without bolus. Pembrolizumab continued concurrently; she had already tolerated immune checkpoint inhibition for approximately 9 months without bullous disease.
- After only 7 fractions, two bullae appeared on the contralateral untreated breast. By fraction 13, a bulla had appeared inside the irradiated breast; radiotherapy was stopped after 26 Gy in 13/25 fractions, and pembrolizumab was held after five adjuvant cycles.
- Disease then generalized rather than remaining confined to the radiation field, with perioral, abdominal and other cutaneous lesions. The photographs in the report show substantial denuded areas within the treated breast together with distant bullous lesions, a distribution inconsistent with ordinary radiation dermatitis.
- Initial biopsy demonstrated subepidermal vesicular dermatosis compatible with bullous pemphigoid or a bullous drug eruption, without histologic evidence of radiation dermatitis. Eight months later, repeat biopsy with direct immunofluorescence demonstrated linear IgG and C3 deposition along the dermoepidermal junction, confirming bullous pemphigoid.
- Treatment included prednisone approximately 1 mg/kg/day, topical corticosteroids and antimicrobial wound care. Persistent disease ultimately required dupilumab, but response remained incomplete and intermittent flares continued more than one year after the initial eruption.
- Immune checkpoint inhibitor-associated bullous pemphigoid is itself uncommon, reported in <1% of clinical-trial populations, and typically develops after several months. Prior literature also documents radiation-associated cases, but the authors interpret the unusually early onset, out-of-field distribution and prior pembrolizumab tolerance as supporting a possible radiotherapy–PD-1 interaction rather than proving one.
CLINICAL TAKEAWAY
New blistering during radiotherapy plus checkpoint inhibition should not automatically be labelled severe radiation dermatitis, particularly when lesions occur outside the treatment field. Early dermatology assessment and biopsy matter because bullous pemphigoid can become prolonged enough to terminate both radiotherapy and immunotherapy; however, this case cannot establish that concurrent treatment causally increases risk.