Discussion

BP is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. It is characterised by autoantibodies against structural proteins of the dermal–epidermal jonction and responsible for localised or generalised bullous lesions.^{Reference Schmidt and Zillikens4}

RT is one of several physical agents including ultraviolet light, thermal burns and skin grafts that have been reported to induce BP in normal skin.^{Reference Danescu, Chiorean, Macovei, Sitaru and Baican5} Radiation-induced bullous pemphigoid (RIBP) affects mainly women with breast carcinomas,^{Reference Campa, Mansouri, Wilcox and Griffin6–Reference Cabrera-Rodriguez, Munoz-Garcia, Quiros Rivero, Ropero Carmona and Rios Kavadoy8} but it has been reported also with other cancers (vulva, cervix, lung and esophagus).^{Reference Nguyen, Kwan and Ahmed9}

Mul et al., reported a large series of BP associated with radiotherapy. BP occurred usually more than 1 year after radiotherapy, only 5/27 patients developed BP within weeks. No dose threshold was found, BP was observed after 20 Gy (three cases), but median dose was 50 Gy.^{Reference Mul, van Geest and Pijls-Johannesma10}

The mechanisms of RIBP remain unclear; radiation tissue damage could induce BP antigens. Another explanation is that patients may already have circulating autoantibodies before RT was performed.

Radiation also influences the levels of matrix metallopeptidase 9 (MMP-9) and the expression of endothelial growth factor (VEGF). It is known that both molecules are involved in the pathophysiology of the blistering.^{Reference Nguyen, Kwan and Ahmed9}

The diagnosis is based on histopathological examination which revealed subepidermal blisters, dermal papillae and the epidermis is preserved.^{Reference Schmidt and Zillikens4}

Therapy for RIBP does not differ from that of ‘de novo’ BP, treatment consists mainly of the administration of local corticosteroids, oral corticosteroids and immunosuppressive treatments depending on the extension of the disease with favourable outcome within weeks.^{Reference Schmidt and Zillikens4,Reference Joly, Roujeau and Benichou11}

In our case, Trastuzumab was administered concomitantly with Docetaxel and BP appeared after the eighth cycle, but we cannot rule out that it may have caused BP or there have been any synergistic effect between RT and Trastuzumab. In the literature, only PB due to programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors has been described.^{Reference Lopez, Khanna, Antonov, Audrey-Bayan and Geskin12} As far as we know, no reported study has established any link between induced BP and Trastuzumab. However, few cases of RRD induced by adjuvant Trastuzumab have been previously reported.^{Reference Chung, Stuart and Keyes13,Reference Moon, Koo, Suh, Yoon, Bae and Lee14} Indeed, RRD is defined as the development of skin reactions in a previously irradiated area after exposure to a recall-triggering drug. Anti-cancer agents are the most commonly involved drugs. The diagnosis of RRD should be considered in patient developing a skin reaction in a previously irradiated area that was normal prior to the introduction of a new drug. RRD can also appear after several exposures to triggering drugs.^{Reference Camidge and Price15} Dermatological reactions may include maculopapular eruptions, erythema, vesicle formation, hemorrhage and necrosis. The time interval between completion of radiation therapy and the recall reaction ranged from days to years. There are no specific therapies for RRD, corticosteroids and non-steroidal anti-inflammatory agents could be used or lesions may resolve spontaneously if the reaction is not severe.^{Reference Azria, Magné and Zouhair16}