SAN ANTONIO — When a child presents with mucositis of two or more sites with no prescription drug history, think reactive infectious mucocutaneous eruption (RIME). 

RIME usually occurs after a bacterial or viral respiratory infection and is most often seen in children and adolescents, although it can also affect adults, according to Anna Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington, DC. 

“It is often triggered by Mycoplasma pneumoniae, but you do not need to identify an infection to make the diagnosis,” she said at the Society of Dermatology Physician Associates (SDPA) 23^rd Annual Fall Dermatology Conference. “It's kind of like Stevens-Johnson syndrome and toxic epidermal necrolysis, but with scant skin involvement in some cases, but in other cases just as much skin involvement.”

Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), the first episode of RIME often requires hospital admission, aggressive pain control, hydration, supplemental nutrition with a nasogastric tube, and sometimes total parenteral nutrition — as well as immunosuppression with agents such as steroids, cyclosporine, and etanercept. Early diagnosis is important to minimize potential long-term disease complications, which can include ocular scarring, genital phimosis/scarring, and post-traumatic stress disorder. 

According to a retrospective cohort study of 50 patients at Boston Children’s Hospital, RIME recurs in 8%-38% of patients and is usually less severe on subsequent presentation, often involving the oral mucosa only. 

Kirkorian discussed a 5-year-old boy admitted to Children’s National with “very brisk, extensive, sheet-like erythema that was very concerning” and mucositis of the lips, yet no visible signs of infection. This was during a period of high norovirus activity, and family members mentioned that everyone else but the patient had a bout with gastroenteritis the previous week. The child was the only one who didn’t get sick and had no diarrhea, Kirkorian said. 

All routine infectious disease tests were negative, including a respiratory viral panel; COVID-19 polymerase chain reaction (PCR) from the nasopharynx; adenovirus, Epstein-Barr virus, and cytomegalovirus PCR blood test; QuantiFERON-TB Gold test; herpes simplex virus (HSV) and varicella-zoster virus PCR tests of the skin and blood; and bacterial cultures of blood, respiratory specimens, and urine. 

However, testing of the boy’s stool sample was positive for norovirus. “We think the mechanism [of RIME] is that is these children are overreacting to their infection,” Kirkorian said. “They are mounting an excellent immune response, so much so that it leads to RIME.”

The child required intubation in the PICU and was hospitalized for many weeks. “This can be a really bad disease, but he’s now clear,” Kirkorian said.

In the retrospective study from Boston Children’s Hospital, oral lesions were present in 96% of cases, while 99% had an infectious prodrome, followed by ocular (76%), genital (52%), and cutaneous (52%) involvement. The authors also found that RIME recurrence was associated with significant psychiatric complications. For example, 33% of patients reported anxiety and/or depressive symptoms after RIME onset compared with 23% of patients with isolated disease (P = .014). 

Kirkorian noted that any child who presents with RIME should undergo HSV testing to rule out herpetic gingivostomatitis, a manifestation of HSV-1 that is characterized by high-grade fever and painful oral lesions. Herpetic gingivostomatitis can first present as cold sores and affected individuals “get a terrible crusted presentation,” she said.

Kirkorian had no disclosures to report. 

Doug Brunk is a San Diego-based medical journalist.