AREAS OF FOCUS
Autoinflammatory Syndromes
Some children develop frequent fevers, on a rhythm almost predictable enough to mark on a calendar, with no infection to explain them. For many of these children, the cause is an autoinflammatory syndrome, a condition in which the body’s innate immune system, the oldest in evolution and most immediate line of defense, triggers inflammation even when there is nothing to fight. The result is recurring episodes of fever and inflammation, often with the child feeling well in between. These conditions are uncommon, frequently misread as one infection after another, and an active area of medical discovery, with new syndromes still being identified.
A different kind of immune problem
Autoinflammatory syndromes are not the same as autoimmune diseases, even though the names sound alike. In an autoimmune disease such as lupus, the immune system produces antibodies and targeted immune cells that attack the body’s own tissues. In an autoinflammatory syndrome, the problem lies in the innate immune system, the rapid, general response that reacts to threats without producing antibodies or targeted immune cells. That system misfires, driving inflammation on its own without a specific target. This is why these conditions often produce fever, rashes, joint pain, or abdominal pain in recurring bouts rather than the steady, tissue-specific damage seen in autoimmune disease.
The pattern that points to a syndrome
The clue is rarely a single fever; it is the pattern. A child has repeated episodes of fever that follow a rhythm, last a few days, and resolve, only to return weeks later. Standard workups for infection keep coming back negative. The most common of these conditions in children is periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA), which brings recurring fevers along with mouth sores, sore throat, and swollen neck glands, usually beginning in the preschool years. Others, such as familial Mediterranean fever, are inherited and run in families. Because a single episode looks like an ordinary childhood illness, the pattern often takes time and repetition to recognize, and children are frequently treated for infection after infection before the real cause is found.
How it is diagnosed and treated
Diagnosis rests on recognizing the pattern, reviewing the timing and features of episodes, assessing markers of inflammation during and between episodes, and, for inherited syndromes, conducting genetic testing. A pediatric rheumatologist is trained to recognize the pattern of these diseases, whereas others may see a string of unrelated illnesses. Treatment has advanced considerably. Some syndromes respond to well-established medications, while others are treated with targeted therapies called biologics that block the specific inflammatory signals driving the disease. This approach has transformed the outlook for children with more serious forms. Many children do very well once the condition is correctly identified.
How Dr. Shulman approaches it
Autoinflammatory disease is central to Dr. Shulman’s work as a physician-scientist. His research has helped characterize systemic autoinflammatory conditions and the immune signatures that define them, work that sharpens how these diseases are recognized and treated. He brings that same investigative habit to the clinic, where recognizing an autoinflammatory syndrome often means seeing a pattern others have missed. It is exactly the sort of puzzle, where the mechanism underlying the symptoms is the whole story, that he explores in his forthcoming book, Cramp: A Doctor’s Notes on Pain.
Frequently Asked Questions
What is an autoinflammatory syndrome?
An autoinflammatory syndrome is a condition in which the innate immune system, the body’s immediate, general defense, triggers inflammation without an infection or other external cause. The most recognizable feature is recurring fever that follows a pattern, often accompanied by other signs such as rash, joint pain, or abdominal pain, with the child feeling well between episodes. These conditions are uncommon, and researchers have identified roughly sixty of them so far, with more still being discovered.
How is an autoinflammatory syndrome different from an autoimmune disease?
The two sound similar but involve different parts of the immune system. Autoimmune diseases, such as lupus or juvenile arthritis, involve the immune system producing antibodies and targeted cell responses that attack the body’s own tissues. Autoinflammatory syndromes involve the innate immune system misfiring, causing inflammation without a specific target and without those antibodies or targeted cell responses. In practical terms, autoinflammatory conditions tend to cause recurring episodes of fever and inflammation rather than the ongoing, tissue-specific damage more typical of autoimmune disease.
My child keeps getting fevers with no infection. What could it be?
Recurring fevers without an infectious cause often prompt evaluation for an autoinflammatory syndrome, though other causes are possible. What helps a doctor most is a record of the episodes: how often they occur, how long they last, what other symptoms appear, and how the child is between episodes. That timeline often turns a series of seemingly separate illnesses into a recognizable condition, so a repeating pattern of unexplained fevers is a reason to see a doctor who can assess the episodes together.
What is PFAPA?
PFAPA is the most common autoinflammatory syndrome in children. The name stands for its main features: periodic fever, along with mouth sores, sore throat, and swollen glands in the neck. It usually begins between the ages of two and five and follows a strikingly regular pattern. It is not caused by infection and is not contagious. Children with PFAPA grow and develop normally and are healthy between episodes. It often improves on its own over time, and treatment can shorten or ease the episodes in the meantime.
Are autoinflammatory syndromes treatable?
Yes, treatment has improved significantly. The approach depends on the specific syndrome. Some are managed with well-established anti-inflammatory medications, while others respond to targeted biologic therapies that block the specific immune signals driving the disease. For many of the more serious inherited syndromes, these targeted treatments have dramatically changed what life looks like for affected children. The first and most important step is an accurate diagnosis, which determines the right treatment.
What kind of doctor diagnoses autoinflammatory syndromes?
Pediatric rheumatologists diagnose and manage these conditions because they specialize in immune-driven inflammatory diseases. Because a single fever episode can mimic an ordinary illness, these syndromes are often recognized only when specialists review the full pattern over time. If a child has repeated, unexplained fevers that follow a rhythm, a pediatrician can refer the family to a pediatric rheumatologist to evaluate the episodes together and test for the specific conditions involved.
For appointments or clinical questions, please contact Rady Children’s Health Orange County (formerly CHOC).