Chou Shaun, Zhao Cathy, Hwang Shelley Ji Eun, Fernandez-Penas Pablo
Tissue Pathology and Diagnostic Oncology, Westmead Hospital, Sydney, Australia.
Department of Dermatology, Westmead Hospital, Sydney, Australia.
J Cutan Pathol. 2017 Oct;44(10):851-856. doi: 10.1111/cup.13013. Epub 2017 Aug 29.
Immune checkpoint agents targeting programmed cell death-1 protein (PD1) or cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) receptors are increasingly utilized in treatment of advanced malignancies. However, these immunotherapies are commonly associated with idiosyncratic cutaneous adverse reactions. Thus, recognition and awareness of these reactions are necessary.
We reviewed the skin biopsies of all patients on anti-PD1 therapy with or without ipilimumab who developed lichenoid inflammation and included those with microscopic suprabasal or intraepidermal clefts.
Four patients presented with interface dermatitis with microscopic intraepidermal clefts. In 2 patients, the clefts were well developed and had some acantholytic cells while the other 2 appeared to be spongiosis or inflammation related. Immunofluorescence was negative in 1 patient. None of them had clinical findings in keeping with paraneoplastic pemphigus (PP) and the symptoms improved with either topical corticosteroid or withdrawal of immunotherapy.
Lichenoid drug reaction occurring in patients receiving anti-PD1 therapy may be associated with microscopic suprabasal or intraepidermal clefting. The clinical course was similar to lichenoid drug reactions without clefting even though some lesions may resemble PP microscopically.
靶向程序性细胞死亡蛋白1（PD1）或细胞毒性T淋巴细胞相关蛋白4（CTLA-4）受体的免疫检查点药物越来越多地用于治疗晚期恶性肿瘤。然而，这些免疫疗法通常与特异性皮肤不良反应相关。因此，认识和了解这些反应很有必要。
我们回顾了所有接受抗PD1治疗（无论是否联用伊匹单抗）且发生苔藓样炎症的患者的皮肤活检样本，纳入了那些在显微镜下有基底层上或表皮内裂隙的患者。
4例患者表现为伴有显微镜下表皮内裂隙的界面性皮炎。其中2例患者的裂隙很明显，并有一些棘层松解细胞，而另外2例似乎与海绵形成或炎症有关。1例患者免疫荧光检查为阴性。他们均无符合副肿瘤性天疱疮（PP）的临床表现，症状通过局部使用糖皮质激素或停用免疫疗法后得到改善。
接受抗PD1治疗的患者发生的苔藓样药物反应可能与显微镜下基底层上或表皮内裂隙有关。尽管有些病变在显微镜下可能类似于PP，但临床病程与无裂隙的苔藓样药物反应相似。
