10.5826/dpc.1203a105
text/xml
2160-9381
1922
en
Aurora Alessandrini
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
PD-1 inhibitors, dermatomyositis, paraneoplastic, capillaroscopy, breast cancer, immune-related adverse events
Is a Triggering Role or a Causative Role of PD-1/PDL-1 Inhibitors in the Development of Paraneoplastic Dermatomyositis?
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2022-07-28
2021-08-02
2022-07-28
2023-06-06
e2022105
Dermatol Pract Concept
Aurora Alessandrini
2022/07/28
10.5826/dpc.1203a105
e2022105
Dermatology -IRCCS Policlinico di Sant’Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Italy
2160-9381
PD-1 inhibitors, dermatomyositis, paraneoplastic, capillaroscopy, breast cancer, immune-related adverse events
en
e2022105
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 Paraneoplastic Dermatomyositis. Int J Mol Sci. 2020;21(6):2178. DOI: 10.3390/ijms21062178. PMID: 32245283; PMCID:PMC7139382.
Is a Triggering Role or a Causative Role of PD-1/PDL-1 Inhibitors in the Development of Paraneoplastic Dermatomyositis?
https://dpcj.org/index.php/dpc/article/download/1922/1663
             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                                                             to drug. Dermatologic examination revealed marked butter-
                                                                         fly-facial edema with periocular swelling, erythematous-vi-
The use of immune checkpoint inhibitors therapy in cancers               olaceous plaques of the face, upper chest and back. (Figure
is widely diffuse but the dermatologic immune-related ad-                1A). Erythematous papules coalescing into plaques of the
verse events (irAEs) are not completely characterized. We                metacarpophalangeal and proximal interphalangeal joints
present the first case of paraneoplastic dermatomyositis trig-           were detected (Figure 1B). Hemorrhagic onycholysis and
gered by atezolizumab.                                                   periungual erythema were detected by capillaroscopy that
                                                                         revealed capillary loss, tortuosity, ramified, enlarged capil-
                                                                         laries, and microhemorrhages (Figure 1, C and D). A skin
Case presentation
                                                                         biopsy from a papule of the back of the hand showed an
A 53-year-old woman affected by ductal infiltrative breast               interface dermatitis and focal mucin deposition in the der-
cancer underwent mastectomy and lymphadenectomy, fol-                    mis. Laboratory testing revealed positive ANA (1:320),
lowed adjuvant chemotherapy. Later she started paclitaxel                normal CPK (212 U/l), mild increased serum aldolase
weekly and atezolizumab after 2 months. At the fifth infu-               (15.5 U/l), normal transaminases. Given the clinical presen-
sion of atezolizumab she developed a skin rash attributed                tation, capillaroscopy, histopathology and ANA positivity




Research Letter | Dermatol Pract Concept. 2022;12(3):e2022105                                                                          1
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).



we made the diagnosis of dermatomyositis. Between myo-                   Conclusions
sitis-specific antibodies requested anti-TIF ƴ antibodies were
significantly positive (negative anti-Ro and anti-JO). Sys-                  PD-1/PDL-1 inhibitor immunotherapy represents a
temic prednisone 50 mg daily and intravenous immunoglob-                 successful treatment for advanced malignancies; it can be
ulins were prescribed with improvement of the clinical signs             associated with lots of irAEs, among which dermatomyo-
(Figure 2).                                                              sitis. Guidelines recommend temporary or permanent drug



2                                                                            Research Letter | Dermatol Pract Concept. 2022;12(3):e2022105
interruption according to the severity of the skin reac-            This case adds new findings to the literature regarding
tion [1]. Besides being drug-induced, dermatomyositis is a       dermatomyositis associated with PD-1/PDL-1 inhibitors.
well described paraneoplastic disease in ovarian and breast      PD-1/PDL-1 inhibitors could have a triggering role rather
cancer. The patient described in our report had the exposure     than a causative role in the development of dermatomyosi-
to atezolizumab and breast cancer, which are both risk fac-      tis. Clinicians should be aware that facing a patient affected
tors for the development of dermatomyositis.                     by metastatic cancer treated with PD-1/PDL-1 inhibitors,
   At the beginning we believed that dermatomyositis could       cutaneous adverse events such dermatomyositis may be not
be drug induced, due to the latency between the drug infusion    related to the treatment but also to the underlying disease,
and the onset of the reaction, and the strong association be-    preventing the interruption of safety treatments.
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     References
classical paraneoplastic dermatomyositis. Paraneoplastic ori-    1. Messer A, Drozd B, Glitza IC, Lu H, Patel AB. Dermatomy-
gin was supported by the presence of all the criteria proposed      ositis associated with nivolumab therapy for melanoma: a
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was near the beginning of the cancer and following the same         2020;26(8):13030/qt4c21b068. PMID: 32941716.
                                                                 2. Didona D, Fania L, Didona B, Eming R, Hertl M, Di Zenzo
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                                                                    G. Paraneoplastic Dermatoses: A Brief General Review and
ulation but strictly associated to tumors, as cancer occur in
                                                                    an Extensive Analysis of Paraneoplastic Pemphigus and Para-
14.8% of dermatomyositis patients [2]. The detection of an-         neoplastic Dermatomyositis. Int J Mol Sci. 2020;21(6):2178.
ti-TIF ƴ antibodies, that are positive in 42%-100% of parane-       DOI: 10.3390/ijms21062178. PMID: 32245283; PMCID:
oplastic dermatomyositis, confirmed our diagnosis [1].              PMC7139382.




Research Letter | Dermatol Pract Concept. 2022;12(3):e2022105                                                                 3
