PMID- 33942396
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1440-1789 (Electronic)
IS  - 0919-6544 (Print)
IS  - 0919-6544 (Linking)
VI  - 41
IP  - 4
DP  - 2021 Aug
TI  - Pembrolizumab-caused polyradiculoneuropathy as an immune-related adverse event.
PG  - 266-272
LID - 10.1111/neup.12729 [doi]
AB  - Immune-related adverse events (irAEs) commonly involve the gastrointestinal 
      tract, endocrine glands, skin, and liver, and rarely the nervous system. The 
      pathomechanism of irAEs in the nervous system is unclear, and so characterizing 
      these severe toxic effects is a priority, even if irAEs are uncommon in the 
      nervous system. Our patient presented subacute muscle weakness and dysesthesia 
      with colitis as irAEs caused by pembrolizumab, one of the anti-programmed death-1 
      (PD-1) antibodies. Electromyography revealed abundant fibrillations and 
      fasciculations of upper and lower extremities and severe reduction in motor unit 
      potentials; however, antineutrophil cytoplasmic antibodies, rheumatoid factor, 
      autoantibodies against Hu and Yo, and anti-ganglioside antibodies, such as GQ1b, 
      were undetectable in the serum. Although he was treated with high-dose 
      glucocorticoids, antibiotics, and a monoclonal anti-tumor necrosis factor alpha 
      (TNFalpha) antibody, he developed colonic perforation. The total colorectal resection 
      was performed, and the resected colon showed mucosal defect and perforation. He 
      died of lung aspergillosis. Postmortem examination revealed CD8-positive 
      lymphocyte infiltration around neurons of dorsal root ganglia. The sciatic nerve 
      displayed the widening of myelin laminae and thinning of myelinated fibers but 
      not a decrease in the density of myelinated nerve fibers. In the sural nerve, the 
      density of myelinated fibers slightly decreased, and some fibers showed less 
      densely myelinated laminae. Drug safety information, including previous 
      randomized trials of anti-PD-1 and anti-cytotoxic T-lymphocyte-associated 
      antigen-4 (CTLA-4) antibodies, showed that patients treated with anti-PD-1 
      antibodies appeared to have more frequent and severe peripheral neuropathies 
      compared to those in patients who received anti-CTLA-4 antibodies (1.59% vs. 
      0.69%; Fisher exact test, P < 0.001; three severe events vs. zero severe events). 
      The present results and drug safety information suggest that the pathomechanism 
      of irAEs caused by anti-PD-1 antibodies is different from that by anti-CTLA-4 
      antibodies. The neurological irAEs might be clues to solving the pathomechanism 
      of irAEs.
CI  - (c) 2021 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Society of Neuropathology.
FAU - Kurashige, Takashi
AU  - Kurashige T
AUID- ORCID: 0000-0002-5206-5979
AD  - Department of Neurology, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Mito, Mineyo
AU  - Mito M
AD  - Department of Respiratory, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Yamamoto, Hideki
AU  - Yamamoto H
AD  - Department of Diagnostic Pathology, National Hospital Organization Kure Medical 
      Center and Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Sugiura, Tomohito
AU  - Sugiura T
AD  - Department of Neurology, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Onoe, Takashi
AU  - Onoe T
AD  - Department of Surgery, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Kuraoka, Kazuya
AU  - Kuraoka K
AD  - Department of Surgery, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Nakano, Kikuo
AU  - Nakano K
AD  - Department of Respiratory, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
FAU - Torii, Tsuyoshi
AU  - Torii T
AD  - Department of Neurology, National Hospital Organization Kure Medical Center and 
      Chugoku Cancer Center, Kure, Hiroshima, Japan.
LA  - eng
GR  - Tsuchiya Foundation/
PT  - Case Reports
DEP - 20210503
PL  - Australia
TA  - Neuropathology
JT  - Neuropathology : official journal of the Japanese Society of Neuropathology
JID - 9606526
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/adverse effects
MH  - Humans
MH  - Male
MH  - *Peripheral Nervous System Diseases
MH  - *Polyradiculoneuropathy
MH  - Programmed Cell Death 1 Receptor
PMC - PMC8453985
OTO - NOTNLM
OT  - PD-1
OT  - immune-checkpoint inhibitor
OT  - immune-related adverse event
OT  - subacute sensorimotor neuronopathy
EDAT- 2021/05/05 06:00
MHDA- 2022/01/14 06:00
PMCR- 2021/09/21
CRDT- 2021/05/04 07:12
PHST- 2020/12/29 00:00 [revised]
PHST- 2020/09/10 00:00 [received]
PHST- 2021/01/01 00:00 [accepted]
PHST- 2021/05/05 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/05/04 07:12 [entrez]
PHST- 2021/09/21 00:00 [pmc-release]
AID - NEUP12729 [pii]
AID - 10.1111/neup.12729 [doi]
PST - ppublish
SO  - Neuropathology. 2021 Aug;41(4):266-272. doi: 10.1111/neup.12729. Epub 2021 May 3.