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Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report

Overview of attention for article published in Journal for Immunotherapy of Cancer, August 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (72nd percentile)
  • Average Attention Score compared to outputs of the same age and source

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31 Dimensions

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Title
Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report
Published in
Journal for Immunotherapy of Cancer, August 2018
DOI 10.1186/s40425-018-0396-9
Pubmed ID
Authors

Jacob Appelbaum, David Wells, Joseph B. Hiatt, Gideon Steinbach, F. Marc Stewart, Hannah Thomas, Paul Nghiem, Raj P. Kapur, John A. Thompson, Shailender Bhatia

Abstract

Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC). A 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a 'burned out' phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified. GI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings.

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X Demographics

The data shown below were collected from the profiles of 11 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 71 100%

Demographic breakdown

Readers by professional status Count As %
Other 10 14%
Researcher 10 14%
Student > Master 6 8%
Student > Doctoral Student 6 8%
Student > Postgraduate 3 4%
Other 11 15%
Unknown 25 35%
Readers by discipline Count As %
Medicine and Dentistry 29 41%
Nursing and Health Professions 4 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Biochemistry, Genetics and Molecular Biology 2 3%
Computer Science 2 3%
Other 4 6%
Unknown 27 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 January 2023.
All research outputs
#5,324,727
of 25,461,852 outputs
Outputs from Journal for Immunotherapy of Cancer
#1,373
of 3,436 outputs
Outputs of similar age
#95,435
of 345,790 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#17
of 31 outputs
Altmetric has tracked 25,461,852 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,436 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.7. This one has gotten more attention than average, scoring higher than 60% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 345,790 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.