10.5826/dpc.1202a45
text/xml
2160-9381
1787
en
Fernando Gruber Velasco
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
adverse event
Ribociclib-Induced Vitiligo: A Case Report
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2022-05-02
2021-05-12
2022-05-02
2022-05-24
e20220045
Dermatol Pract Concept
Fernando Gruber Velasco
2022/05/02
10.5826/dpc.1202a45
e20220045
Department of Dermatology, Hospital Universitario Severo Ochoa,  Leganés (Madrid), Spain
2160-9381
adverse event
en
e20220045
Ribociclib-Induced Vitiligo: A Case Report
https://dpcj.org/index.php/dpc/article/download/1787/1562
                    Dermatology Practical & Conceptual


              Ribociclib-induced Vitiligo: a Case Report
       Nicolás Silvestre Torner1, Antonio Aguilar Martínez1, María José Echarri González2,
          Sergio Tabbara Carrascosa1, Jorge Román Sainz1, Fernando Gruber Velasco1


1 Department of Dermatology, Hospital Universitario Severo Ochoa, Leganés (Madrid), Spain.
2 Department of Oncology, Hospital Universitario Severo Ochoa, Leganés (Madrid), Spain.



Key words: vitiligo, ribociclib, selective cyclin-dependent kinase 4/6 inhibitors, breast cancer, adverse event
Citation: Silvestre-Torner N, Aguilar-Martínez A, Echarri-González MJ, Tabbara-Carrascosa S, Román-Sainz J, Gruber-Velasco F.
Ribociclib-induced vitiligo: a case report. Dermatol Pract Concept. 2022;12(2):e2022045. DOI: https://doi.org/10.5826/dpc.1202a45
Accepted: July 29, 2021; Published: April, 2022
Copyright: ©2022 Silvestre-Torner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution
License 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: Nicolás Silvestre Torner, Department of Dermatology. Hospital Universitario Severo Ochoa. Avenida de Orellana.
Zip code 28911. Leganés (Madrid). Spain. E-mail: nicolassilvestretorner@gmail.com



Introduction                                                               Discussion
Selective cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i)                Vitiligo is an acquired pigmentary autoimmune disorder
– ribociclib, palbociclib and abemaciclib – are a novel thera-             consisting of the development of hypopigmented macules
peutic option for breast cancer [1]. CDK 4/6is are well toler-             due to the selective loss of melanocytes. The cause of vitiligo
ated and have shown a manageable safety profile, with mild                 remains unknown. Vitiligo-like lesions have been reported as
hematological, gastrointestinal and cutaneous adverse events               an AE in oncological patients treated with anti-programmed
(AE). Vitiligo-like lesions are a dermatologic AE exception-               death-1/ programmed death-ligand 1 (PD-1/PD-L1) im-
ally reported with CDK 4/6is use [2].                                      munotherapies (pembrolizumab, nivolumab), as well as in
                                                                           patients treated with tyrosine-kinase inhibitors (imatinib,
                                                                           cabozantinib, pazopanib) [2]. It is considered an indicator
Case Presentation
                                                                           of survival benefit in melanoma patients treated with an-
A 70-year-old woman presented with a 6-week history of as-                 ti-PD-1/PD-L1 immunotherapies.
ymptomatic facial hypopigmented spots. For the last 8 months,                  Selective CDK 4/6is are currently approved by the US Food
she was receiving treatment with letrozole and ribociclib for a            and Drug Administration and the European Medicines Agency
hormone receptor-positive (HR-positive) and human epider-                  for the treatment of patients with HR-positive, HER2-negative
mal growth factor receptor-2-negative (HER2-negative) met-                 advanced or metastatic breast cancer. Hematologic toxicity,
astatic breast cancer. Dermatological examination revealed                 gastrointestinal disturbances and fatigue are the most frequent
unpigmented, well-defined macules distributed symmetrically                side effects of this class of agents [1]. The most common der-
in the neck and the face, with affectation of hair follicle (Fig-          matological adverse event is alopecia, which might be increased
ure 1, A and B). The Wood lamp examination showed bright                   by the association of endocrine therapy. Moreover, pruritus
white and sharply delineated lesions (Figure 2). Based on                  and a maculopapular rash have also been reported as cutane-
these findings, a diagnosis of vitiligo was made.                          ous adverse reactions in patients treated with ribociclib [1,2].



Research Letter | Dermatol Pract Concept. 2022;12(2):e2022045                                                                             1
Figure 1. (A,B) Clinical images. Achromic sharply demarcated macules in the neck, cheeks and ears, with affectation of the hair follicle.


                                                                            Treatment of vitiligo induced by CDK 4/6i is challeng-
                                                                        ing. Similar therapeutic strategies followed in other vitiligo
                                                                        patients can be performed. However, immunosuppressants
                                                                        and biological therapies should be avoided in oncological
                                                                        patients. Partial response has been achieved with topical
                                                                        immunosuppressants in combination with oral corticoste-
                                                                        roids [2].


                                                                        Conlusions
                                                                        Depigmentation may cause psychological distress and may
                                                                        decreased quality of life. Therefore, oncological patients
                                                                        treated with CDK 4/6is should be informed about this po-
Figure 2. Clinical image. Bright white and sharply delineated le-       tential AE and should be referred to a dermatologist for ac-
sions showed with Wood lamp.                                            curate diagnosis and treatment.

    Vitiligo-like lesions have been described in patients
treated with CDK 4/6is too, mostly in relation to ribociclib
                                                                        References
[2]. Although the pathogenic mechanism between CDK 4/6is                 1. Rascon K, Flajc G, De Angelis C, Liu X, Trivedi MV, Ekinci E.
and vitiligo is still unclear, it has been classified as a class-re-        Ribociclib in HR+/HER2- Advanced or Metastatic Breast Can-
lated AE. The cell-cycle arrest and consequent apoptosis in-                cer Patients. Ann Pharmacother. 2019;53(5):501–509. DOI:
                                                                            10.1177/1060028018817904. PMID: 30522347
duced by CDK 4/6is [1], may lead to a premature death of
                                                                         2. Sollena P, Nikolaou V, Soupos N, et al. Vitiligo-like lesions in patients
melanocytes, that clinically manifests as achromic lesions.
                                                                            with advanced breast cancer treated with cycline-dependent kinases
The prognostic meaning of vitiligo lesions in patients treated              4 and 6 inhibitors. Breast Cancer Res Treat. 2021;185(1):247-253.
with CDK 4/6is remains still unclear.                                       DOI: 10.1007/s10549-020-05914-w. PMID: 32914354.




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