Acta Dermato-Venereologica 97-4 | Page 34

SHORT COMMUNICATION

Advances in dermatology and venereology Acta Dermato-Venereologica

Development of Papulopustular Rosacea during Nivolumab Therapy for Metastatic Cancer

Emilie BOUSQUET 1, Allison ZARBO 2, Emilie TOURNIER 3, Christine CHEVREAU 4, Julien MAZIERES 1, Mario E. LACOUTURE 5 and Vincent SIBAUD 6 *

1

Pulmonary Medicine Unit, Hôpital Larrey, Centre Hospitalier Universitaire Toulouse, Université de Toulouse III, Toulouse, France, 2 Department of Dermatology, Henry Ford Hospital Detroit, Michigan, USA, 3 Department of Pathology, Institut Universitaire du Cancer, Toulouse Oncopole, Centre Hospitalier Universitaire de Toulouse, 4 Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer, Toulouse Oncopole, Toulouse, France, 5 Dermatology Service, Memorial Sloan Kettering Cancer Center New York, NY, USA, and 6 Departments of Oncodermatology and Clinical Research, Institut Claudius Regaud, Institut Universitaire du Cancer, Toulouse Oncopole, 1 rue Irene Joliot- Curie, FR-31059 Toulouse cedex, France. * E-mail: sibaud. vincent @ iuct-oncopole. fr Accepted Nov 8, 2016; Epub ahead of print Nov 9, 2016

Dermatological toxicities represent the most frequent immune-related adverse events( irAEs) induced by immune checkpoint inhibitors( 1, 2). Safety profiles for anti-CTLA-4 inhibitors( ipilimumab) and agents targeting the programmed cell death( PD-1) receptor( nivolumab, pembrolizumab) appear to be very similar, yet a lower frequency is observed with the latter( 2). A non-specific maculopapular rash represents the most frequent cutaneous toxicity of anti-PD-1 inhibitors, with a calculated all-grade incidence of 14.3 % and 16.7 % for nivolumab and pembrolizumab, respectively( 3). These lesions mostly remain mild / moderate, self-limiting, and manageable with topical and / or oral steroids. Other dermatological complications can also occur, including pruritus, xerosis, alopecia, mucosal involvement, autoimmune disorders and vitiligo, the latter being exclusively described in patients treated for melanoma( 1 – 3). More recently, additional skin adverse events have been described, including lichenoid reactions, blistering disorders or occurrence and exacerbation of psoriasis( 1 – 4). We report here 6 patients who developed a mid-facial rash suggestive of papulopustular rosacea, triggered or exacerbated by nivolumab therapy, which has not been reported so far in association with anti-PD-1 therapy.

Table I. Clinical description of reported patients

Case No./ Sex / Age, years

Underlying malignancies

Treatment

Time to onset

CASE REPORTS

All patients( 5 men, 1 woman) were treated for different types of metastatic solid cancers( Table I). Lesions occurred after 1 – 19 cycles of nivolumab therapy( 3 mg / kg every 2 weeks). They were mostly localized on the medial part of the face, with a characteristic combination of papules and pustules on an underlying erythema, consistent with papulopustular rosacea. Symptoms were of mild intensity in all cases( grade 1 papulopustular rash)( Fig. 1a) except for one patient, who presented with an intolerable grade 2 toxicity( Fig. 1b). Lesions were easily managed with symptomatic treatment( topical metrodinazole and / or oral doxycycline), leading to a significant improvement in all cases. Nivolumab therapy was delayed in one patient and resumed after one cycle. Cutaneous biopsy was performed on the patient with grade 2 toxicity, which demonstrated characteristic histopathological features of papulopustular rosacea, with a predominant perivascular and perifollicular CD3 + T-cell infiltrate, associated with small and superficial dilated blood vessels. In addition, PD-L1 immunostaining revealed a strong positivity in the perifollicular infiltrate cells( 60 %)( Fig. 2). Close examination of the patients’ history suggested pre-existing erythematotelangiectatic rosacea in 3 patients.

DISCUSSION

Development or exacerbation of papulopustular rosacea with anti-PD-1 therapy has not been described previously. We cannot, however, rule out the possibility that this event is under-reported during its development

Temporary discontinuation, topical metronidazole, oral doxycycline( 100 mg / day)

Regression

8 cycles Grade 1 Topical metronidazole Complete resolution c Yes

Complete resolution c

a Following National Cancer Institute CTCae V4.02. b erythemato-telangiectatic rosacea. c 4 and 8 weeks after the last dose of nivolumab, respectively.

Pre-existing rosacea b

Yes

No

This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2566 Acta Derm Venereol 2017; 97: 539 – 540