Severe Oral Mucositis: A Rare Adverse Event of Pembrolizumab
July 2018 | Volume 17 | Issue 7 | Case Report | 807 | Copyright © 2018
Margo H. Lederhandler MD, Anthony Ho BA, Nooshin Brinster MD, Roger S. Ho MD, Tracey N. Liebman MD, Kristen Lo Sicco MD
The Ronald O. Perelman Department of Dermatology, New York University, New York, NY
Treatment of malignancy with anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors can cause mucocutaneous side effects resulting from T cell activation. Due to their recent development, the full side effect profile remains to be fully elucidated, however dermatologic adverse events are most common. The main oral toxicities of these immune checkpoint inhibitors include: xerostomia, dysgeusia, and lichenoid reactions. Oral mucositis occurs more rarely in the setting of PD-1 inhibition, and few other reports of a Grade 3 or higher, severe, stomatitis have been reported in the literature. We present a case of a 78-year-old woman with Grade 3 ulcerative oral mucositis that occurred 13 months after initiation of PD-1 inhibitor, pembrolizumab, for the treatment for lung adenocarcinoma. She was successfully treated with prednisone, and pembrolizumab was temporarily held by her oncologist. Physicians should be aware of the possibility of severe mucositis in the setting of PD-1 inhibitors, as well as the management. J Drugs Dermatol. 2018;17(7):807-809.
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A 78-year-old Chinese woman with a history of metastatic lung adenocarcinoma presented to the hospital for evaluation of an acute, painful erosive eruption involving the intraoral mucosa and lips of two weeks duration. She was unable to tolerate oral intake of food or liquid due to the severity of her pain. She denied fever, cough, lesions elsewhere on the body, or other systemic complaints. Thirteen months prior to presentation, she was started on pembrolizumab every three weeks for metastatic lung adenocarcinoma, and several days prior to the onset of her symptoms she received her last dose. There were no other new medications.Physical examination revealed diffuse erosions with hemorrhagic crusting, within the vermillion border on the lower lip (Figure 1A). Scattered on the tongue and buccal mucosa were numerous erosions (Figure 1B). The ocular and genital mucosae were clear. The remainder of the skin exam was unremarkable.Laboratory workup was notable for seropositivity for herpes simplex virus (HSV) IgG and IgM and Mycoplasma pneumoniae (MP) IgG and IgM. Viral culture and HSV polymerase chain reaction (PCR) studies of the lip were negative. Paraneoplastic pemphigus IgG antibodies on indirect immunofluorescence (IIF) were negative.Two punch biopsies were obtained from the lower lip, one lesional for hematoxylin and eosin (H&E) and one perilesional for direct immunofluorescence (DIF). Histopathology demonstrated an ulcer bed with underlying pale edematous stroma with increased number of capillaries and a mixed inflammatory cell infiltrate comprised predominately of lymphocytes, histiocytes, and neutrophils. Epithelium was not present in multiple examined sections (Figure 2). DIF detected no specific immunoreactants for C3, IgA, IgG, IgM, or fibrinogen.While inpatient, she was treated with empiric intravenous acyclovir, dexamethasone solution swish and spit, and topical mupirocin ointment mixed with triamcinolone 0.1% ointment. Oral prednisone 80 mg daily was initiated during hospitalization, and a taper was continued after discharge. She resumed pembrolizumab with her oncologist one day after discharge.The patient was seen two weeks after hospital discharge, and examination revealed persistence of mucositis, although with mild improvement (Figure 1C) and no other mucocutaneous involvement. She continued on the prednisone taper in addition to fluocinonide 0.05% gel. She was prescribed oral azithromycin and a second course of acyclovir in the setting of seropositive HSV IgM and MP IgM antibodies. Pembrolizumab was held in light of severe Grade 3 mucositis. Her symptoms had nearly resolved at her six-week follow-up visit (Figure 1D).
Immune checkpoint inhibition is a novel treatment strategy intended to activate the immune system against malignancy.1 Pembrolizumab is an IgG4 antagonist monoclonal antibody to programmed-cell-death-1 (PD-1) receptor approved by the FDA in 2014.1,2 When PD-1 binds to programmed-cell-death-ligand-1 (PD-L1), T-cell proliferation is suppressed; thus tumor cells that express PD-L1 are protected from cytotoxic