Immunotherapy-related adverse effects: how to identify and treat them in the emergency department
When patients with cancer present to the emergency department with therapy-related symptoms, it’s crucial to ascertain at the outset whether the treatment is with chemotherapy or immunotherapy so that the appropriate symptom treatment can be initiated as early as possible. In this interview, Dr David Henry and Dr Maura Sammon discuss some of the most common immunotherapy-related side effects – lung, gastrointestinal, rash, and endocrine-related problems – and Dr Sammon describes in detail how physicians in the ED would triage and treat the patient. However, the overarching takeaway is the importance of communication: first, between the oncologist and patient, so that the patient is aware of these nuances in advance of an emergency, and second, between the ED physician and the treating oncologist soon after the patient has presented and undergone an initial assessment.
Dr Henry is the Editor-in-Chief of The Journal of Community and Supportive Oncology (www.jcso-online.com).This is an edited version of the interview podcast.
LISTEN TO THE INTERVIEW here.
Correspondence
David H Henry, MD; David.Henry@uphs.upenn.edu
Disclosures
Dr Sammon and Dr Henry report no disclosures/conflicts of interest.
Citation JCSO 2018;16(4):e216-e220
©2018 Frontline Medical Communications
doi https://doi.org/10.12788/jcso.0408
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Then I’m going to talk to the patient about symptomatic treatment. I’m going to talk to them about oral hydration, a bland diet. Avoid using loperamide or any other antidiarrheal medicines, because that could decrease the frequency of stools but mask more severe symptoms that they may be having.
If I have a patient who is having more than 4 stools above their daily baseline and it’s been happening 4 to 6 stools a day for more than a week, I’m going to be sending those studies off, and I’m going to be having a conversation with the treating oncologist to find out if they want me to start the patient on steroids immediately, or if they want to wait for the test results to come back and have the steroids started as an outpatient.
These moderate patients can maybe wait a day until these test results come back. Those who are having more than 7 stools above baseline per day, peritoneal signs, ileus, or fever, are the patients you should worry about. You need to admit them for IV hydration. You need to do the stools, so you might need to keep them in the hospital until you find the results of the stool studies. You need to rule out perforation.
,You may be starting steroids on these patients sooner rather than later. They’re going to be getting systemic corticosteroids at about 1-2 mg/kg of prednisone equivalent, assuming there is no perforation and their stool studies are negative. If they are unstable, though, they are really going to need high-dose corticosteroids. They are going to need methylprednisolone, 125 mg IV, to evaluate for their responsiveness. These folks really need to be treated as inpatients, and they need to have their oncologists involved early on with their treatment.
DR HENRY Yes. I couldn’t agree with you more. When I talk to the diarrhea side effect patients that we see, I tend to think it’s a curse. It’s volume. It’s calories. It’s electrolytes. The number of stools you’re mentioning, it is almost certainly going to need admission to rule out other causes. Then, if it’s the checkpoint inhibitor, the steroid antidotes.
Let’s move on to the rash. This is another organ system that can be affected by immunotherapy. What is your approach when you see a generalized body rash in a patient on one of these drugs who is sent to the ED?
DR SAMMON I am obviously going to be ruling out other causes first, but generally you’re going to see a maculopapular rash. It may be itchy. It may be burning. Patients will often describe it as just sort of having a tight sensation. I’m going to be looking at them a little bit like I look at a burn patient. What is their total body surface area that’s involved? If they’ve got less than 30% of their total body surface area involved, that’s considered a mild reaction.
For those folks, I’m not going to use systemic steroids, but I can give them some topical steroids, and I can give them some Benadryl, some diphenhydramine, and really treat them symptomatically as well as ensuring that they have early follow-up to make sure this isn’t progressing. Once we get between 30% and 50% body area, we’re talking about a moderate toxicity. If these patients are not improving rapidly with just withholding the drug, they need systemic corticosteroids.
We usually treat them at about 0.5-1 mg/kg body weight a day of prednisone equivalent. Just as with burn patients, these patients’ symptoms can become very severe. You can see signs of blistering, dermal ulceration, necrotic, bolus, hemorrhagic lesions (Figure 2, A-D).1 These folks can have very difficult-to-manage fluid balances, and they’re at very high risk for skin infections as well. They need to be treated as inpatients. If possible, you might want to consider sending these patients to a burn unit. They need systemic corticosteroids, 1-2 mg/kg per day, and they need careful monitoring for signs of dehydration, electrolytic abnormalities, and/or skin infections. They need excellent wound care.
