Serum sickness-like reactions may emerge with biologic treatment
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Key takeaways:
- The patient was on omalizumab for asthma for 5 years before symptoms emerged.
- Symptoms resolved after switching to tezepelumab treatment.
- Arthralgias and constitutional symptoms may indicate serum sickness.
BOSTON — Physicians should consider delayed hypersensitivity reactions such as serum sickness when patients experience symptoms during biologic treatment, according to a poster presented at the CHEST Annual Meeting.
“As we use more and more of these monoclonal antibodies, it’s just going to become more important for us to monitor,” Lt. Kathryn Hughes, MD, fellow, pulmonary and critical care department, Naval Medical Center San Diego, told Healio.
Although rare, the researchers noted, serum sickness and serum sickness-like reactions may occur with the use of omalizumab (Xolair; Genentech, Novartis) and other biologic medications.
“We look a lot for type 1 hypersensitivity reactions in our clinic and for injection reactions, and we think a little bit less about these more delayed reactions,” she continued. “I think it’s something to keep an eye out for.”
Hughes described a female patient, aged 45 years, with asthma in addition to chronic urticaria and allergic bronchopulmonary aspergillosis with symptom control for all three syndromes with 5 years of treatment with omalizumab.
Additional medications included a fluticasone, umeclidinium and vilanterol inhaler as well as fexofenadine and omeprazole.
“She came back to the clinic and said that over the past 6 months, she had been experiencing monthly arthralgias, debilitating malaise, low-grade fevers and abdominal discomfort,” Hughes said.
“Along this time as well, she had experienced gradual worsening of her chronic symptoms of cough, wheezing and urticaria and, again, those had been previously very well controlled for the past 5 years,” she continued.
During the physical exam, providers found bibasilar wheezing on auscultation in addition to joint tenderness without effusions or erythema in her knees, wrists or ankles, although there was some active synovitis.
The patient experienced these symptoms, particularly in her knees, within a few days of her monthly omalizumab treatment. They would improve gradually within a week.
The complete blood count, comprehensive metabolic panel, inflammatory markers and radiographs all were unremarkable, Hughes said.
“We gave her a short course of oral clinical steroids for treatment of an asthma exacerbation and noted that her respiratory symptoms, as well as all of her joint symptoms, dramatically improved,” Hughes said.
The providers suspected a serum-like sickness reaction and changed therapy from omalizumab to tezepelumab (Tezspire; Amgen, AstraZeneca). The arthralgias, malaise and abdominal discomfort all resolved once omalizumab was discontinued.
“Then her respiratory symptoms gradually became controlled over the course of three doses,” Hughes said.
Immune complex depositions occur in various organs and manifest in a wide range of reactions including fevers, rashes and constitutional symptoms along with vasculitis and renal and other organ failures in serum sickness, Hughes said.
“Patients will have laboratory evidence of acute inflammation,” she continued.
Serum sickness-like reactions are less well understood in the immunology literature, Hughes added, but appear to be less severe.
“They tend to have relatively normal labs and no organ damage,” Huges said. “And they, in research, at least, have not identified immune complexes. So, it is difficult to tease out what exactly is driving that.”
Yet serum sickness and serum sickness-like reactions both tend to see complete resolution once treatment with the offending drug has ceased, she said. The researchers do not recommend rechallenges if treatment must stop.
“You can use steroids to help bridge those symptoms until that drug is out of the system,” Hughes said. “In some mild cases, you can try to continue the drug if it’s still efficacious.”
Serum sickness and serum sickness-like reactions tend to emerge once the efficacy of the biologic starts to wane, Hughes said, possibly correlating with the development of the neutralizing antibodies that some biologics can induce in patients.
“Maybe both of these phenomena are being driven by the same process that decreased efficacy,” Hughes suggested.
Most of the sparse case reports in the literature describe reactions with omalizumab and dupilumab (Dupixent; Regeneron, Sanofi), Hughes said, theorizing that they are most common in the literature because they have been available longer.
“I guess that tezepelumab will also induce this in some patients, but just hasn’t been around long enough,” she said.
Hughes also cautioned that there are no data suggesting that if a patient develops serum sickness in response to one biologic, it will develop in response to other drugs too. She also said that these reactions, although rare, can be seen with all monoclonal antibodies.
Further, Hughes said this particular case was interesting because the patient had developed these reactions after being so well controlled for 5 years without any of these symptoms.
“You can develop serum sickness at any point in the treatment,” Hughes said.
If the patient would have presented with these symptoms after just, for example, the second dose of omalizumab, Hughes said, the serum sickness would have been very difficult to identify.
“Like, are these just side effects of the medication? Or is this more of an immunologic phenomenon?” Hughes said. “The fact that she developed them after 5 years would suggest more of an immunologic phenomenon.”
Additionally, Hughes noted that the symptoms with which the patient presented were similar to those noted in the drug insert for its side effects.
“There are cases where it could be very difficult to distinguish,” she said.
As a result, Hughes advised physicians to consider serum sickness and serum sickness-like reactions when patients on biologics present with these symptoms.
“These delayed hypersensitivity reactions are rare and maybe a little bit more difficult to diagnose because they don’t happen while the patients in the clinic are getting their medication,” she said. “But they are something that we need to be thinking about as we start these drugs in more and more patients.”
For more information:
Lt. Kathryn Hughes, MD, can be reached at kathryn.g.hughes4.mil@health.mil.