Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy

Oncologist. 2019 Jul;24(7):872-876. doi: 10.1634/theoncologist.2018-0722. Epub 2019 Apr 1.

Abstract

Background: Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life-threatening immune-related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies.

Case presentation: We describe herein a patient with metastatic melanoma who developed epididymo-orchitis followed by encephalitis while receiving pembrolizumab. The patient developed testicular pain and fever after his third dose of pembrolizumab; ultrasound evaluation demonstrated bilateral epididymo-orchitis. He then developed headaches, fever, and altered mental status over the next week and was admitted to the hospital. Lumbar puncture revealed inflammatory changes consistent with meningoencephalitis; he did not improve with broad-spectrum antibiotics, and an extensive workup for infectious etiologies, including cerebrospinal fluid testing using a clinical metagenomic next-generation sequencing assay, was negative. He received high-dose steroids for suspected autoimmune encephalitis, and both his orchitis and meningoencephalitis improved rapidly after one dose. He fully recovered after a 5-week taper of oral steroids.

Discussion: Here, we report a case of epididymo-orchitis complicating immune checkpoint inhibitor therapy. This patient subsequently developed severe encephalitis but rapidly improved with steroids. Clinicians should be aware of rare complications of these agents.

Key points: Epididymo-orchitis is a rare and potentially life-threatening complication of anti-programmed death protein 1 (anti-PD-1) therapy.For patients on anti-PD-1 therapy who develop either epididymo-orchitis or epididymitis without clear infectious cause, immune-related adverse events should be considered in the differential diagnosis.If severe, epididymo-orchitis related to anti-PD-1 therapy may be treated with high-dose corticosteroids.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents, Immunological / adverse effects*
  • Encephalitis / chemically induced
  • Encephalitis / drug therapy
  • Encephalitis / pathology*
  • Epididymitis / chemically induced
  • Epididymitis / drug therapy
  • Epididymitis / pathology*
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / secondary
  • Orchitis / chemically induced
  • Orchitis / drug therapy
  • Orchitis / pathology*
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Uveal Neoplasms / drug therapy*
  • Uveal Neoplasms / secondary

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab

Supplementary concepts

  • Uveal melanoma