Experts Explain How to Differentiate Serious Infectious Disease from Rheumatic Conditions in Children

Some infectious diseases can mimic rheumatic disorders, and knowing what to look for and what questions to ask can help rheumatologists determine the most likely cause of a patient’s symptoms.

During the Monday, Nov. 18, session Infectious Mimics of Pediatric Rheumatic Disease in Children: An Interactive Discussion, Roberta DeBiasi, MD, MS, FAAP, highlighted a number of possibilities to consider when a young patient presents with a generalized rash and systemic hyperinflammation. She is Chief of the Division of Infectious Diseases and the Robert H. Parrot Professor of Pediatric Research, Children’s National Hospital and Research Institute, and Professor of Pediatrics, Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine.

The session will be available on-demand to all registered ACR Convergence 2024 participants through Oct. 10, 2025, by logging into the meeting website.

The major diseases frequently seen by Dr. DeBiasi and her colleagues are staphylococcal or streptococcal toxin-mediated disease, multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection, Kawasaki disease, viral syndromes, and Rickettsial infections.

“It’s important to think of all these, because many are life-threatening if they are not picked up,” Dr. DeBiasi said.

In addition to a red rash and hyperinflammation, other visual cues to look for include erythroderma reddening of the skin that resembles a sunburn (staphylococcal), a strawberry tongue (scarlet fever and Kawasaki), and blisters with a red border (hand, foot, and mouth disease).

“With staphylococcal scarlet fever, the rash is more diffused and has more like a sandpaper feel to it,” Dr. DeBiasi explained. “It often has an area of whiteness around the mouth, called circumoral pallor, or Pastia’s lines, which are accentuations of red in a linear fashion in the areas where there is a fold, either in the arms or on the neck folds.”

MIS-C was not even on the radar when Children’s National Hospital saw a “landslide” of about 250 cases in 2020, Dr. DeBiasi said. A task force was formed to rapidly identify children with the difficult-to-treat syndrome, which often includes symptoms of fever, abdominal pain, and organ dysfunction.

“Essentially, there is one form (of MIS-C) that looks identical to Kawasaki,” Dr. DeBiasi said. “It’s very hard to tell them apart.”

Further complicating diagnosis, there is no test for either MIS-C or Kawasaki disease.

“I should say that MIS-C, we now know, is very uncommon if you’ve had vaccination,” Dr. DeBiasi said. “So, we often will ask that right away. If they’re vaccinated, it goes way down on our differential (diagnosis).”

According to the U.S. Centers for Disease Control and Prevention, a child may become ill with MIS-C weeks after being infected with SARS-CoV-2, the virus that causes COVID-19. The infection could have occurred by having contact with an asymptomatic person, and, in some cases, the child and parents may be unaware of an infection.

In the first of two interactive exchanges during the session, Ekemini Ogbu, MD, MSc, Pediatric Rheumatologist and Assistant Professor at Cincinnati Children’s Hospital Medical Center, presented the case of an 11-year-old girl with trisomy 21 who was diagnosed at the age of 6 years with rheumatoid factor-negative Down syndrome polyarthropathy. The patient was hospitalized with jaundice, a need for oxygen, and a 15-day history of consistent fever. She was eventually diagnosed with histoplasmosis that was complicated by secondary hemophagocytic lymphohistiocytosis (HLH) and thrombotic microangiopathy.

Histoplasmosis is the most common endemic mycosis in the United States and mostly affects the lungs, Dr. Ogbu explained.

“For the rheumatologist’s spectrum, most of the time these patients would have arthritis and erythema nodosum, but they could also have fibrosing mediastinitis, which we can be consulted for, in addition to the hyperinflammation,” she said.

A second interactive presentation was given by Joyce Hui-Yuen, MD, MS, Associate Professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, and Associate Professor of Pediatrics, Zucker School of Medicine at Hofstra-Northwell, who spoke about leprosy in children. Also known as Hansen’s disease, it is often found in warm climates.

“There are 100 to 250 new cases per year in the U.S., apparently much less up here with a much colder climate,” Dr. Hui-Yuen said.

The early signs of leprosy include a rash, which can be reddish or appear as pale skin patches or bumps. Leprosy also can involve the nasal mucosa, result in loss of feeling in the fingers and toes, can often affect the bones, and sometimes includes erythema nodosom and thickened dermis.