Información de la revista
Vol. 113. Núm. 4.
Páginas T427-T431 (Abril 2022)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 113. Núm. 4.
Páginas T427-T431 (Abril 2022)
Case and Research Letter
Open Access
[Translated article] Psoriasis and Anti-PD-1 and Anti-PD-L1 Immunotherapy: Three Cases, a Review of the Literature, and a Proposed Management Algorithm
Psoriasis y anti-PD1/anti-PDL1: presentación de tres casos, revisión de la literatura y propuesta de algoritmo de manejo
Visitas
...
E. Sánchez-Martíneza,
Autor para correspondencia
eva.sanchez.m.92@gmail.com

Corresponding author.
, M. Sáez-Bellóa, S. Ochenduszkob, A. Mateu-Puchadesa
a Servicio de Dermatología, Hospital Universitario Doctor Peset, Valencia, Spain
b Servicio de Oncología Médica, Hospital Universitario Doctor Peset, Valencia, Spain
Contenido relaccionado
E. Sánchez-Martínez, M. Sáez-Belló, S. Ochenduszko, A. Mateu-Puchades
Información del artículo
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Figuras (2)
Tablas (1)
Table 1. Patients with psoriasis induced or exacerbated by anti-PD1/anti-PDL1 published in the literature as cases or series and their principal characteristics.
Texto completo
To the Editor,

Anti-PD1 and anti-PDL1 immune checkpoint inhibitors constitute a new, efficacious therapeutic weapon in the treatment of cancer. Nevertheless, these drugs produce immune-related adverse effects, inherent to their antitumor mechanism of action, which often involve the skin and can lead to their withdrawal. Dermatologic toxicity due to anti-PD1 and anti-PDL1 may manifest in highly varied ways, including psoriasis.1 The pathogenesis of psoriasis induced by anti-PD1 and anti-PDL1 appears to be attributed to an overactivation of Th1, Th17, and Th22 lymphocytes secondary to inactivation of the PD1 immunomodulatory pathway.2

In our hospital, we assessed 3 patients who developed psoriasis as a result of treatment with anti-PD1 and anti-PDL1 for gallbladder cancer, cancer of the larynx, and a metastatic melanoma (Fig. 1). We also performed a search of the literature for published cases of psoriasis due to anti-PD1 and anti-PDL1 and we recorded the following variables: age, sex, type of tumor, type of anti-PD1/PDL1, dosage regimen used, time to appearance of lesions, personal history of psoriasis, treatment administered, interruption of treatment with anti-PD1/PDL1, and response of tumor to immunotherapy. Finally, we propose an algorithm for the treatment of psoriasis induced by anti-PD1 and anti-PDL1.

Figure 1.

Patients in our department with psoriasis due to anti-PD1/anti-PDL1. (A) Guttate psoriasis. (B) Palmoplantar psoriasis. (C) Psoriasis plaques and vitiligo.

(0,15MB).

Our patients and the cases published in the literature account for 43 cases of psoriasis induced or exacerbated by anti-PD1 (26 by nivolumab and 12 by pembrolizumab) and anti-PDL1 (3 by atezolizumab and 2 by durvalumab) (Table 1).3–7 The mean age of the patients was 65.7years (35–87 y), with a predominance of males (34/43, 79%). The most frequent types of neoplasia were melanoma and lung cancer, which together accounted for 18 out of 43 cases (41.9%), followed by urothelial carcinoma (3/43, 7%), renal cell carcinoma, diffuse large B cell lymphoma, tonsil cancer, and squamous cell carcinoma of the larynx (1 case out of 43 each, 2.3%). The mean time from instatement of immunotherapy to appearance of the psoriasis lesions was 9.6weeks. Eleven of the 43 cases stated that they had no personal history of psoriasis (25.6%) and 14 of the 43 presented an exacerbation of their previous psoriasis with anti-PD1/anti-PDL1 treatment (32.6%), although this information was not recorded in many of the published studies. In nearly half of patients, the psoriasis was managed with topical treatment alone (20/43, 46.5%). The most commonly used systemic therapies were oral retinoids (9/43, 20.9%), phototherapy and systemic corticosteroids (5/43, 11.6%, in both cases). Two cases were treated with methotrexate (2/43, 4.7%) and 2 isolated cases received apremilast and secukinumab. Withdrawal of immunotherapy due to psoriasis was not necessary in 15 patients (34.9%), whereas treatment was suspended temporarily in 6 patients (14%) and permanently in 5 (11.6%).

Table 1.

Patients with psoriasis induced or exacerbated by anti-PD1/anti-PDL1 published in the literature as cases or series and their principal characteristics.

No.  Age, y/sex  Neoplasm  Anti-PD1/anti-PDL1, dosage regimen  Latency, wk  History of psoriasis  Treatment of psoriasis  Interruption of anti-PD1/anti-PDL1  Tumor response to anti-PD1/anti-PDL1  Lead author, year 
80/M  Melanoma  Nivolumab, 2mg/kg every 3 weeks  12  No  Systemic corticosteroids  No  Yes  Ohtsuka, 2015 
65/M  Melanoma  Nivolumab, 2mg/kg every 3 weeks  Yes  Topical corticosteroids plus calcipotriol and phototherapy, with no response. Oral retinoids with response  No  No Information  Kato, 2015 
45/M  Renal cell carcinoma  Nivolumab, 2mg/kg every 3 weeks  No  Topical corticosteroids plus calcipotriol  Yes, 21 d  Yes  Ruiz-Bañobre, 2017 
87/M  Melanoma  Nivolumab, 2mg/kg every 3 weeks  Yes  Systemic corticosteroids  Yes  No Information  Matsumura, 2015 
80/F  Melanoma  Pembrolizumab, no information  3–6  No Information  Topical corticosteroids plus calcipotriol  Yes  Yes  Totonchy, 2016 
67/M  Lung carcinoma  Pembrolizumab, no information  Yes  Oral retinoids  Yes, 4 wk  No Information  Sahuquillo-Torralba, 2016 
NA  No Information  Pembrolizumab, no information  Yes  Topical corticosteroids plus calcipotriol and systemic corticosteroids  Yes, 1 wk  No Information  Sanlorenzo, 2015 
8–24  Mean, 64.8 [35–87]/F (2), M (15)  Melanoma (9), lung carcinoma (8)  Pembrolizumab (5), nivolumab (11), atezolizumab (1), no information  No information  No Information  Topical corticosteroids (10), systemic corticosteroids (1), oral retinoids (5), and phototherapy (1)  No Information  No Information  Bonigen, 2017 
25  67/M  Lung carcinoma  Nivolumab, 2mg/kg every 3 weeks  No  Topical corticosteroids plus calcipotriol  No  No Information  Yamamoto, 2018 
26  67/M  Melanoma  Pembrolizumab, 2mg/kg every 3 weeks  15  Yes  Oral retinoids and phototherapy  Yes, 4 wk  Yes  Phadke, 2016 
27–31  Mean, 66 [60–72]/F (1), M (4)  Lung carcinoma (3), urothelial carcinoma (1), tonsil cancer (1)  Pembrolizumab (1), nivolumab (2), durvalumab (2), no information  2–8  Yes (3), No (2)  Topical corticosteroids plus calcipotriol (1), phototherapy (3), methotrexate plus systemic corticosteroids (1)  Yes (1), No (4)  No Information  Voudouri, 2017 
32  89/M  Melanoma  Nivolumab, 2mg/kg every 3 weeks  No  Topical corticosteroids plus calcipotriol  No  No  Murata, 2017 
33  80/M  Lung carcinoma  Nivolumab, 2mg/kg every 3 weeks  16  No  Topical corticosteroids, systemic corticosteroids plus methotrexate  Yes, 4 wk  Yes  Law-Pingman, 2016 
34  65/F  Melanoma  Nivolumab, 2mg/kg every 3 weeks  20  Yes  Topical corticosteroids plus calcipotriol  Yes, spacing doses 3 weeks apart  Yes  De Bock, 2018 
35  53/M  Diffuse large B-cell lymphoma  Nivolumab, 2mg/kg every 3 weeks  12  No  Topical corticosteroids plus calcipotriol  Yes  No  Panayotis, 2018 
36  74/F  Lung carcinoma  Nivolumab, 2mg/kg every 3 weeks  12  Yes  Topical corticosteroids plus calcipotriol with no response Apremilast with response  No  Yes  Fattore, 2019 
37  51/F  Lung carcinoma  Nivolumab, 2mg/kg every 3 weeks  12  No  Topical corticosteroids plus calcipotriol  No  Yes  Guven, 2019 
38  69/M  Lung carcinoma  Pembrolizumab, 200mg every 3 weeks  12  Yes  Topical corticosteroids plus calcipotriol  No  No Information  Scanfi, 2019 
39  63/F  Lung carcinoma  Pembrolizumab, 200mg every 3 weeks  12  Yes  Topical corticosteroids plus calcipotriol with no response Secukinumab with response  No  Yes  Monsour, 2019 
40  75/M  Urothelial carcinoma  Atezolizumab, 1200mg every 3 weeks  Yes  Topical corticosteroids plus calcipotriol plus systemic corticosteroids.  Yes  No  Santos-Juanes, 2019 
41  73/M  Urothelial carcinoma  Atezolizumab, 1200mg every 3 weeks  16  No  Phototherapy  No  Yes  Our study 
42  54/M  Laryngeal squamous cell carcinoma  Nivolumab, 2mg/kg every 3 weeks  12  Yes  Oral retinoids  No  Yes  Our study 
43  77/M  Melanoma  Nivolumab, 2mg/kg every 3 weeks  20  No  Topical corticosteroids plus calcipotriol  No  Yes  Our study 

Abbreviations: F indicates female; M, male.

The response of the cancer to the anti-PD1 and anti-PDL1 is poorly described in these patients. The available data describe a good response in 12 patients and a lack of response in 3. Nevertheless, no correlation appears to exist between the antitumor response and the severity of the psoriasis, as occurs in vitiligo associated with the use of nivolumab for the treatment of melanoma.8

For the treatment of drug-induced psoriasis early recognition, and withdrawal, if possible, of the causal agent is generally recommended, together with the standard therapeutic regimen for psoriasis, in accordance with guidelines.9 The use of cyclosporin is contra-indicated in psoriasis with an underlying cancer. The safety of TNF inhibitors and methotrexate is the subject of debate and little data is available on apremilast and other biological drugs.10 Based on these data, we propose an algorithm for the treatment of patients with psoriasis due to anti-PD1 and anti-PDL1 (Fig. 2). The first point is the need for the oncologist to take a personal and family history of psoriasis from the patient. When psoriasis appears, the patient should be assessed rapidly by the dermatologist. The treatment considered must take into account the extension (PASI) and effect on quality of life (DLQI questionnaire) of the patient's psoriasis. We therefore recommend prescribing topical treatment in mild psoriasis and prioritizing phototherapy and oral retinoids when systemic therapy is required, owing to the immunosuppressant effect of these drugs, due to the possible negative effect on the course of the cancer. In the event of a lack of response or contra-indication, apremilast, methotrexate, or biological treatments may be proposed after agreement with the oncologist.

Figure 2.

Proposed algorithm for managing psoriasis induced or exacerbated by anti-PD1/anti-PDL1.

(0,26MB).

Dermatologists must learn to recognize and treat the immune-associated cutaneous adverse effects due to anti-PD1 and anti-PDL1, which include psoriasis. Given its frequency, we highlight the need for periodic dermatologic follow-up of these patients. Cooperation with oncology is also essential to accelerate the diagnosis and provide the patients with the best therapeutic option to keep them free of lesions but without negatively affecting the neoplastic disease.

Conflict of interests

The authors declare that they have no conflict of interest.

References
[1]
E. Coleman, C. Ko, F. Dai, M.M. Tomayko, H. Kluger, J.S. Leventhal.
Inflammatory eruptions associated with immune checkpoint inhibitor therapy: a single-institution retrospective analysis with stratification of reactions by toxicity and implications for management.
J Am Acad Dermatol, 80 (2019), pp. 990-997
[2]
N. Matsumura, M. Ohtsuka, N. Kikuchi, T. Yamamoto.
Exacerbation of psoriasis during nivolumab therapy for metastatic melanoma.
Acta Derm Venereol, 96 (2016), pp. 259-260
[3]
M. De Bock, E. Hulstaert, V. Kruse, L. Brochez.
Psoriasis vulgaris exacerbation during treatment with a PD-1 checkpoint inhibitor: case report and literature review.
Case Rep Dermatol, 10 (2018), pp. 190-197
[4]
D. Fattore, M.C. Annunziata, L. Panariello, C. Marasca, G. Fabbrocini.
Successful treatment of psoriasis induced by immune checkpoint inhibitors with apremilast.
Eur J Cancer, 110 (2019), pp. 107-109
[5]
D. Voudouri, V. Nikolaou, K. Laschos, A. Charpidou, N. Soupos, I. Triantafyllopoulou, et al.
Anti-PD1/PDL1 induced psoriasis.
Curr Probl Cancer, 41 (2017), pp. 407-412
[6]
J. Bonigen, C. Raynaud-Donzel, J. Hureaux, N. Kramkimel, A. Blom, G. Jeudy, et al.
Anti-PD1-induced psoriasis: a study of 21 patients.
J Eur Acad Dermatol Venereol, 31 (2017), pp. e254-e257
[7]
E.P. Monsour, J. Pothen, R.A. Balaraman.
Novel approach to the treatment of pembrolizumab-induced psoriasis exacerbation: a case report.
Cureus, 11 (2019), pp. e5824
[8]
Y. Nakamura, R. Tanaka, Y. Asami, Y. Teramoto, T. Imamura, S. Sato, et al.
Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: a multi-institutional retrospective study.
J Dermatol, 44 (2017), pp. 117-122
[9]
D.M. Balak, E. Hajdarbegovic.
Drug-induced psoriasis: clinical perspectives.
Psoriasis (Auckl), 7 (2017), pp. 87-94
[10]
S.B. Kaushik, M.G. Lebwohl.
Psoriasis: which therapy for which patient: psoriasis comorbidities and preferred systemic agents.
J Am Acad Dermatol, 80 (2019), pp. 27-40
Copyright © 2021. AEDV
Idiomas
Actas Dermo-Sifiliográficas

Suscríbase a la newsletter

Opciones de artículo
Herramientas
es

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?