Pediatric RIME: Report Describes Case Triggered by Norovirus

A rare and devastating pediatric skin condition – severe reactive infectious mucocutaneous eruption (RIME) – may now have an additional, previously undescribed trigger, according to a newly published case report.

Lead author Anna Yasmine Kirkorian, MD, chief of dermatology at Children's National Hospital in Washington, said she wanted to get the word out in part because it seems like RIME is occurring more frequently. "I do feel like we're seeing more cases and from a more diverse number of pathogens," Dr. Kirkorian told this news organization.

There was a decrease in RIME during the early stages of the COVID-19 pandemic when people were isolating more, Dr. Kirkorian said. SARS-CoV-2 has been a trigger for some cases, but she did not find that remarkable, given that respiratory viruses are known RIME precursors. The question is why RIME is being triggered more frequently now that people have essentially gone back to their normal lives, she said.

Dr. Kirkorian and colleagues at Children's National Hospital and George Washington University, Washington, wrote about a 5-year-old boy with norovirus-triggered RIME in a case report published in Pediatric Dermatology.

RIME – previously known as Mycoplasma pneumoniae–induced rash and mucositis (MIRM) – tends to arise after a viral infection, with upper respiratory viruses such as mycoplasma and Chlamydophila pneumoniae, influenza, and enterovirus among the common triggers. "We think this is actually your own immune system overreacting to a pathogen," Dr. Kirkorian said in an interview, adding that the mechanism of RIME is still not understood.

While the norovirus discovery was a surprise, it shows that much is still unknown about this rare condition. "I don't think we know what is usual and what is unusual," Dr. Kirkorian said.

In this case, the boy swiftly declined, with progressive conjunctivitis, high fever, and rapidly developing mucositis. By the time the 5-year-old got to Children's National Hospital, he had a spreading, painful rash, including tense vesicles and bullae involving more than 30% of his total body surface area, and areas of denuded skin on both cheeks and the back of his neck.

He had hemorrhagic mucositis of the lips, a large erosion at the urethral meatus, and hemorrhagic conjunctivitis of both eyes with thick yellow crusting on the eyelids.

The clinicians intubated the boy and admitted him to the intensive care unit. He was given a one-time injection of etanercept (25 mg) followed by 8 days of intravenous cyclosporine at a dose of 5 mg per kilogram, divided twice daily, which helped calm the mucositis and stopped the rash from progressing. There is not an accepted protocol or list of evidence-based therapeutics for RIME, Dr. Kirkorian noted.

The severe eye damage required amniotic membrane grafts. The patient was extubated after 9 days but remained in the hospital for a total of 26 days because he needed to receive nutritional support (the mucositis kept him from eating), and for pain control and weaning of sedation.

As the clinicians searched for a potential triggering virus, they came up empty. Results were negative for adenovirus, Epstein Barr virus, cytomegalovirus, herpes simplex, and varicella zoster. But they noted that the child's household contacts had all been sick a week before with presumed viral gastroenteritis. They decided to run a stool screen and the polymerase chain reaction for norovirus was positive. The boy never had GI symptoms.

Dr. Kirkorian said in the interview that she has seen other RIME cases where a child did not have symptoms associated with the original virus but did have a sudden onset of mucositis.

Although the definition of RIME is evolving, it is defined in part by mucositis in at least two of three areas: the mouth, eyes, and genitals. "Once you have the inflammation of the mucous membranes you should be on alert to think about more serious conditions," like RIME, said Dr. Kirkorian. "Why does it manifest with the mucositis? I don't think we know that," she added.

RIME recurrence has also been vexing for patients, families and clinicians. In May, at the annual Atlantic Dermatology Conference, held in Baltimore, Dr. Kirkorian also discussed an 11-year-old patient who had RIME after SARS-CoV-2 infection early in the pandemic, resulting in a 22-day hospitalization and placement of a peripherally inserted central catheter and a feeding tube. He improved with cyclosporine and was discharged on systemic tacrolimus.

He was fine for several years, until another COVID infection. He again responded to medication. But not long after, an undetermined viral infection triggered another episode of RIME.

Dr. Kirkorian said there is no way to predict recurrence – making a devastating condition all the more worrisome. "Knowing that it might come back and it's totally haphazard as to what might make it come back – that is very stressful for families," she said in the interview.

"Some of the most perplexing patients with RIME are those with recurrent disease," wrote Warren R. Heymann, MD, professor of dermatology and pediatrics at Rowan University, Camden, N.J., wrote in an online column on RIME in the American Academy of Dermatology's "Dermatology World Insights and Inquiries".

"Recurrent RIME is of particular interest, given that we could potentially intervene and prevent additional disease," wrote Camille Introcaso, MD, associate professor of medicine at Rowan University, in response to Dr. Heymann's remarks. "Although multiple possible mechanisms for the clinical findings of RIME have been proposed, including molecular mimicry between infectious agent proteins and keratinocyte antigens, immune complex deposition, and combinations of medication and infection, the pathophysiology is unknown," she added.

In the interview, Dr. Kirkorian said that she and colleagues in the Pediatric Dermatology Research Alliance (PeDRA) are trying to assemble more multicenter trials to assess the underlying pathology of RIME, effectiveness of various treatments, and to "find some predictive factors." Given that RIME is an acute-onset emergency, it is not easy to conduct randomized controlled trials, she added.

Dr. Kirkorian, Dr. Heymann, and Dr. Introcaso report no relevant financial relationships.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

Credits:

Lead image: Science Photo Library/Getty Images

Image 1: Dr A. Yasmine Kirkorian

© 2023  Frontline Medical Communications Inc.

Cite this: Pediatric RIME: Report Describes Case Triggered by Norovirus - Medscape - Jul 21, 2023.