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与帕博利珠单抗治疗相关的爆发性角化棘皮瘤

Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy.

作者信息

Freites-Martinez Azael, Kwong Bernice Y, Rieger Kerri E, Coit Daniel G, Colevas A Dimitrios, Lacouture Mario E

机构信息

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Department of Dermatology, Stanford University School of Medicine, Stanford, California.

出版信息

JAMA Dermatol. 2017 Jul 1;153(7):694-697. doi: 10.1001/jamadermatol.2017.0989.

Abstract

IMPORTANCE

To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab.

OBJECTIVE

To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management.

DESIGN, SETTING, AND PARTICIPANTS: Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs.

INTERVENTIONS

All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery.

RESULTS

Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1-positive) T cells, an immunophenotypic pattern also observed in other cases of anti-PD-1-induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers.

CONCLUSIONS AND RELEVANCE

Pembrolizumab is used in advanced melanoma, advanced non-small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.

摘要

重要性

据我们所知,此前尚无关于接受帕博利珠单抗治疗的患者发生暴发性角化棘皮瘤(KA)的报道。

目的

报告3例连续发生的由帕博利珠单抗诱发的暴发性KA病例及其治疗情况。

设计、背景和参与者:对来自2个中心的3例接受帕博利珠单抗治疗的癌症患者进行病例报告研究,这些患者均发生了暴发性KA。

干预措施

所有3例患者均接受了丙酸氯倍他索软膏和皮损内注射曲安奈德治疗;2例患者还接受了开放性浅表冷冻手术。

结果

3例连续的癌症患者,2例男性和1例女性(中位年龄83岁;范围77 - 91岁),发生了与帕博利珠单抗相关的暴发性KA。所有患者在接受帕博利珠单抗治疗中位13个月(范围4 - 18个月)后,在四肢暴露于阳光的部位突然出现多个皮损。在皮损活检中,在真皮深层观察到苔藓样浸润,主要由CD3 + T细胞、散在的CD20 + B细胞和相对较少的PD - 1 +(程序性细胞死亡1阳性)T细胞组成,这种免疫表型模式在其他抗PD - 1诱导的苔藓样皮炎病例中也有观察到。患者接受了丙酸氯倍他索软膏和皮损内注射曲安奈德治疗,单独使用或与开放性浅表冷冻手术联合使用。所有患者的KA均消退,在密切随访期间未出现新的皮损。所有3例患者均继续接受帕博利珠单抗治疗,未中断,且所有患者的原发性癌症均获得完全缓解。

结论及相关性

帕博利珠单抗用于晚期黑色素瘤、晚期非小细胞肺癌和头颈癌。已经描述了多种皮肤免疫相关不良事件,包括斑丘疹、苔藓样反应、瘙痒和白癜风。本病例系列表明,帕博利珠单抗治疗也可能与具有特征性真皮炎症的暴发性KA相关,单独使用皮质类固醇治疗(外用和皮损内注射)或与冷冻手术联合使用可改善病情,使患者能够继续接受帕博利珠单抗治疗。

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