Autoimmune diseases as noninfectious causes of fever

Fever without infection can be a manifestation of a number of different disorders in children, including various autoimmune and autoinflammatory diseases.

Building a differential diagnosis to guide further evaluation and the need for referral to a subspecialist depends on determining the fever pattern and identifying any associated signs and symptoms, said Kabita Nanda, MD, FAAP, assistant professor of pediatrics, University of Washington, Seattle, in her session “Fever without infection: Autoimmune and autoinflammatory diseases” on Saturday, October 22.

“One of the most important things that pediatricians can do in trying to formulate a strategy to help them diagnose the cause of fever without infection is to ask parents to keep a fever and symptom log,” Nanda told attendees.

“Autoimmune and autoinflammatory diseases are rare causes of fever, but in the absence of infection they should be considered in the differential diagnosis if there is persistent or recurrent fever. After infection has been ruled out and if the symptoms fit the pattern of a possible fever syndrome, it is appropriate to refer the child for further evaluation,” Nanda said.

She discussed how the method for taking temperature may affect what is documented as a fever and described the defining characteristics of the various patterns of fever without infection-recurrent, periodic, and prolonged.

In addition to obtaining a detailed fever and symptom log, pediatricians should conduct a thorough history and physical examination. “Findings from the clinical assessment are key because genetic testing is not always helpful,” Nanda said.

With respect to recognizing findings that should raise suspicion of autoimmune and autoinflammatory diseases, the evaluation should note the child’s growth pattern and any existing or recent rash, enlarged lymph nodes, joint pain or abnormalities, abdominal pain, oral ulcers, or sore throat.

Nanda compared and contrasted the following autoimmune and autoinflammatory conditions associated with fever of unknown origin: systemic-onset juvenile idiopathic arthritis, macrophage activation syndrome, familial Mediterranean fever, cryopyrinopathies, tumor necrosis factor receptor-associated periodic syndrome, and hyper-immunoglobulin D syndrome. She emphasized the importance of diagnosing systemic-onset juvenile idiopathic arthritis because it carries the highest morbidity and mortality risk.

Nanda also highlighted tables and flowcharts published in various articles in the literature that pediatricians can refer to as guides to help with their patient evaluations. 

Ms Krader has 30 years’ experience as a medical writer. She has worked as both a hospital pharmacist and a clinical researcher/writer for the pharmaceutical industry, and is presently a freelance writer in Deerfield, Illinois. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.