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Reporte de caso
Medwave 2020;20(7):e8010 doi: 10.5867/medwave.2020.07.8010
Paniculitis secundaria a terapia target en paciente con melanoma, lo que el dermatólogo debe saber: reporte de un caso
Panniculitis in association with target therapy in melanoma patient, what the dermatologist should know: A case report
Víctor Manubens-Vargas, Manuel Rodríguez-Ortubia, Alejandra Salas-Gianini, Fernando Valenzuela, Laura Carreño-Toro
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Palabras clave: melanoma, panniculitis, BRAF kinases, adverse drug reaction

Abstract

Target therapies are currently a therapeutic option increasingly used for the management of patients with metastatic melanoma. However, there are multiple adverse pharmacological effects associated with their use that have been described. Cutaneous adverse reactions are the most frequent. We report the case of a 55-year-old man with a diagnosis of stage IV BRAFV600E-mutated metastatic cutaneous melanoma undergoing treatment with dabrafenib/trametinib, who consulted due to the development of erythematous nodular lesions in the upper and lower limbs associated with febrile sensation during the course of treatment. Infection was ruled out and a biopsy of the skin lesions was done, which provided the histopathological confirmation of a predominantly septal, granulomatous with leukocytoclastic vasculitis, mixed panniculitis. Panniculitis associated with this therapy has been described in the literature and has been considered an immune-mediated pharmacological adverse effect. It is considered to be related to a better prognosis in the treatment of metastatic melanoma. Consequently, as shown in this case report, target therapy should not be discontinued and symptomatic medication should be given to alleviate patient discomfort. The dermatologist should know and properly interpret this adverse effect and prescribe the most appropriate management for the patient.


 

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Target therapies are currently a therapeutic option increasingly used for the management of patients with metastatic melanoma. However, there are multiple adverse pharmacological effects associated with their use that have been described. Cutaneous adverse reactions are the most frequent. We report the case of a 55-year-old man with a diagnosis of stage IV BRAFV600E-mutated metastatic cutaneous melanoma undergoing treatment with dabrafenib/trametinib, who consulted due to the development of erythematous nodular lesions in the upper and lower limbs associated with febrile sensation during the course of treatment. Infection was ruled out and a biopsy of the skin lesions was done, which provided the histopathological confirmation of a predominantly septal, granulomatous with leukocytoclastic vasculitis, mixed panniculitis. Panniculitis associated with this therapy has been described in the literature and has been considered an immune-mediated pharmacological adverse effect. It is considered to be related to a better prognosis in the treatment of metastatic melanoma. Consequently, as shown in this case report, target therapy should not be discontinued and symptomatic medication should be given to alleviate patient discomfort. The dermatologist should know and properly interpret this adverse effect and prescribe the most appropriate management for the patient.

Autores: Víctor Manubens-Vargas[1], Manuel Rodríguez-Ortubia[1], Alejandra Salas-Gianini[1], Fernando Valenzuela[1], Laura Carreño-Toro[2]

Filiación:
[1] Departamento de Dermatología, Facultad de Medicina, Universidad de Chile, Santiago, Chile
[2] Servicio de Anatomía Patológica, Hospital Clínico Universidad de Chile, Santiago, Chile

E-mail: victor.manubens.v@gmail.com

Correspondencia a:
[1] Santos Dumont 999, Independencia
Santiago, Chile

Citación: Manubens-Vargas V, Rodríguez-Ortubia M, Salas-Gianini A, Valenzuela F, Carreño-Toro L. Panniculitis in association with target therapy in melanoma patient, what the dermatologist should know: A case report. Medwave 2020;20(7):e8010 doi: 10.5867/medwave.2020.07.8010

Fecha de envío: 3/5/2020

Fecha de aceptación: 12/8/2020

Fecha de publicación: 26/8/2020

Origen: No solicitado

Tipo de revisión: Con revisión por pares externa, por tres árbitros a doble ciego

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  1. Sawyers C. Targeted cancer therapy. Nature. 2004 Nov 18;432(7015):294-7. | CrossRef | PubMed |
  2. McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014 Mar;15(3):323-32. | CrossRef | PubMed |
  3. Macdonald JB, Macdonald B, Golitz LE, LoRusso P, Sekulic A. Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways. J Am Acad Dermatol. 2015 Feb;72(2):221-36; quiz 237-8. | CrossRef | PubMed |
  4. Mössner R, Zimmer L, Berking C, Hoeller C, Loquai C, Richtig E, et al. Erythema nodosum-like lesions during BRAF inhibitor therapy: Report on 16 new cases and review of the literature. J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1797-806. | CrossRef | PubMed |
  5. Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019 Aug 15;381(7):626-636. | CrossRef | PubMed |
  6. Hwang SJ, Anforth R, Carlos G, Fernandez-Peñas P. Cutaneous Adverse Events of New Anti-melanoma Therapies: Classification and Management. Actas Dermosifiliogr. 2017 Jan-Feb;108(1):6-16. | CrossRef | PubMed |
  7. Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, et al. Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma. JAMA Dermatol. 2015 Oct;151(10):1103-9. | CrossRef | PubMed |
  8. Choy B, Chou S, Anforth R, Fernández-Peñas P. Panniculitis in patients treated with BRAF inhibitors: a case series. Am J Dermatopathol. 2014 Jun;36(6):493-7. | CrossRef | PubMed |
  9. Consoli F, Manganoni AM, Grisanti S, Petrelli F, Venturini M, Rangoni G, et al. Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy. PLoS One. 2019 Apr 2;14(4):e0214884. | CrossRef | PubMed |
  10. Ben-Betzalel G, Baruch EN, Boursi B, Steinberg-Silman Y, Asher N, Shapira-Frommer R, et al. Possible immune adverse events as predictors of durable response to BRAF inhibitors in patients with BRAF V600-mutant metastatic melanoma. Eur J Cancer. 2018 Sep;101:229-235. | CrossRef | PubMed |
Sawyers C. Targeted cancer therapy. Nature. 2004 Nov 18;432(7015):294-7. | CrossRef | PubMed |

McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014 Mar;15(3):323-32. | CrossRef | PubMed |

Macdonald JB, Macdonald B, Golitz LE, LoRusso P, Sekulic A. Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways. J Am Acad Dermatol. 2015 Feb;72(2):221-36; quiz 237-8. | CrossRef | PubMed |

Mössner R, Zimmer L, Berking C, Hoeller C, Loquai C, Richtig E, et al. Erythema nodosum-like lesions during BRAF inhibitor therapy: Report on 16 new cases and review of the literature. J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1797-806. | CrossRef | PubMed |

Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019 Aug 15;381(7):626-636. | CrossRef | PubMed |

Hwang SJ, Anforth R, Carlos G, Fernandez-Peñas P. Cutaneous Adverse Events of New Anti-melanoma Therapies: Classification and Management. Actas Dermosifiliogr. 2017 Jan-Feb;108(1):6-16. | CrossRef | PubMed |

Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, et al. Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma. JAMA Dermatol. 2015 Oct;151(10):1103-9. | CrossRef | PubMed |

Choy B, Chou S, Anforth R, Fernández-Peñas P. Panniculitis in patients treated with BRAF inhibitors: a case series. Am J Dermatopathol. 2014 Jun;36(6):493-7. | CrossRef | PubMed |

Consoli F, Manganoni AM, Grisanti S, Petrelli F, Venturini M, Rangoni G, et al. Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy. PLoS One. 2019 Apr 2;14(4):e0214884. | CrossRef | PubMed |

Ben-Betzalel G, Baruch EN, Boursi B, Steinberg-Silman Y, Asher N, Shapira-Frommer R, et al. Possible immune adverse events as predictors of durable response to BRAF inhibitors in patients with BRAF V600-mutant metastatic melanoma. Eur J Cancer. 2018 Sep;101:229-235. | CrossRef | PubMed |