Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(3):e2022105 1 Do PD-1/PDL-1 Inhibitors Play a Triggering or Causative Role in the Development of Paraneoplastic Dermatomyositis? Michela Starace1, Francesca Pampaloni2, Miriam Anna Carpanese1, Andrea Sechi1, Francesca Bruni1, Aurora Alessandrini1 1 Dermatology -IRCCS Policlinico di Sant’Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Italy 2 Dermatology Unit, Department of Medicine, University of Padova, Italy Key words: PD-1 inhibitors, dermatomyositis, paraneoplastic, breast cancer, immune-related adverse events Citation: Starace M, Pampaloni F, Carpanese MA, et al. Do PD-1/PDL-1 Inhibitors Play a Triggering or Causative Role in the Development of Paraneoplastic Dermatomyositis? Dermatol Pract Concept. 2022;12(3):e2022105. DOI: https://doi.org/10.5826/dpc.1203a105 Accepted: October 25, 2021; Published: July 2022 Copyright: ©2022 Starace et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/ which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Carpanese Miriam Anna, MD, Dermatology -IRCCS Policlinico di Sant’Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Via Massarenti, 1, 40138 Bologna, Italy, phone: +390512143677 fax: +390512144867 E-mail: miriam.carpanese@gmail.com Introduction The use of immune checkpoint inhibitors therapy in cancers is widely diffuse but the dermatologic immune-related ad- verse events (irAEs) are not completely characterized. We present the first case of paraneoplastic dermatomyositis trig- gered by atezolizumab. Case presentation A 53-year-old woman affected by ductal infiltrative breast cancer underwent mastectomy and lymphadenectomy, fol- lowed adjuvant chemotherapy. Later she started paclitaxel weekly and atezolizumab after 2 months. At the fifth infu- sion of atezolizumab she developed a skin rash attributed to drug. Dermatologic examination revealed marked butter- fly-facial edema with periocular swelling, erythematous-vi- olaceous plaques of the face, upper chest and back. (Figure 1A). Erythematous papules coalescing into plaques of the metacarpophalangeal and proximal interphalangeal joints were detected (Figure 1B). Hemorrhagic onycholysis and periungual erythema were detected by capillaroscopy that revealed capillary loss, tortuosity, ramified, enlarged capil- laries, and microhemorrhages (Figure 1, C and D). A  skin biopsy from a papule of the back of the hand showed an interface dermatitis and focal mucin deposition in the der- mis. Laboratory testing revealed positive ANA (1:320), normal CPK (212 U/l), mild increased serum aldolase (15.5 U/l), normal transaminases. Given the clinical presen- tation, capillaroscopy, histopathology and ANA positivity 2 Research Letter | Dermatol Pract Concept. 2022;12(3):e2022105 Conclusions PD-1/PDL-1 inhibitor immunotherapy represents a successful treatment for advanced malignancies; it can be associated with lots of irAEs, among which dermatomyo- sitis. Guidelines recommend temporary or permanent drug we made the diagnosis of dermatomyositis. Between myo- sitis-specific antibodies requested anti-TIF ƴ antibodies were significantly positive (negative anti-Ro and anti-JO). Sys- temic prednisone 50 mg daily and intravenous immunoglob- ulins were prescribed with improvement of the clinical signs (Figure 2). Figure 1. (A) Facial butterfly-edema, with periocular swelling, erythematous-to-slightly-violaceous plaques sparing the frontal region and the submental area. (B) Erythematous discrete papules coalescing into plaques of the metacarpophalangeal and proximal interphalangeal joints. (C) Capillaroscopic examination: capillary loss, tortuosity, ramified, enlarged and giant capillaries, and microhemorrhages 50X magnifica- tion. (D) 70X magnification Figure 2. The same patient after the therapy with intravenous immunoglobulin: evident improvement on face (A) and hands (B). Research Letter | Dermatol Pract Concept. 2022;12(3):e2022105 3 This case adds new findings to the literature regarding dermatomyositis associated with PD-1/PDL-1 inhibitors. PD-1/PDL-1 inhibitors could have a triggering role rather than a causative role in the development of dermatomyosi- tis. Clinicians should be aware that facing a patient affected by metastatic cancer treated with PD-1/PDL-1 inhibitors, cutaneous adverse events such dermatomyositis may be not related to the treatment but also to the underlying disease, preventing the interruption of safety treatments. References 1. Messer A, Drozd B, Glitza IC, Lu H, Patel AB. Dermatomy- ositis associated with nivolumab therapy for melanoma: a case report and review of the literature. Dermatol Online J. 2020;26(8):13030/qt4c21b068. PMID: 32941716. 2. Didona D, Fania L, Didona B, Eming R, Hertl M, Di Zenzo G. Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Para- neoplastic Dermatomyositis. Int J Mol Sci. 2020;21(6):2178. DOI: 10.3390/ijms21062178. PMID: 32245283; PMCID: PMC7139382. interruption according to the severity of the skin reac- tion  [1]. Besides being drug-induced, dermatomyositis is a well described paraneoplastic disease in ovarian and breast cancer. The patient described in our report had the exposure to atezolizumab and breast cancer, which are both risk fac- tors for the development of dermatomyositis. At the beginning we believed that dermatomyositis could be drug induced, due to the latency between the drug infusion and the onset of the reaction, and the strong association be- tween anti- PD-1/PDL-1 therapy and dermatomyositis. Nev- ertheless, the worsening after drug discontinuation suggested that the anti- PD-1/PDL-1 was only a triggering factor for a classical paraneoplastic dermatomyositis. Paraneoplastic ori- gin was supported by the presence of all the criteria proposed for the diagnosis of paraneoplastic dermatoses. The disease was near the beginning of the cancer and following the same course, moreover dermatomyositis is rare in the general pop- ulation but strictly associated to tumors, as cancer occur in 14.8% of dermatomyositis patients [2]. The detection of an- ti-TIF ƴ antibodies, that are positive in 42%-100% of parane- oplastic dermatomyositis, confirmed our diagnosis [1].