Insight into the Characteristics of Orphan Autoinflammatory Disorders

Research describing clinical characteristics of patients with undefined systemic autoinflammatory diseases (SAIDs) found that patients with pericarditis and intellectual impairment may comprise distinct subsets. The study was conducted by 26 investigators throughout Europe. It evaluated the clinical and genetic data of 187 patients from the Eurofever Registry, an international, web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases. This study included both children and adult patients.¹

Autoinflammatory disorders are a category of diseases distinct from autoimmune diseases. They are characterized by excessive activity of the innate immune system, which causes increased inflammation and tissue damage. Known examples of systemic autoinflammatory disorders include familial Mediterranean fever, cryopyrin-associated periodic fever syndrome, NLRP3-associated autoinflammatory disease, mevalonate kinase deficiency and TNFRSF1A-receptor associated periodic fever syndrome.²

The study’s aim was to describe the clinical characteristics, treatment response and genetics of a large cohort of patients with systemic autoinflammatory disorders, according to study investigators Joost Frenkel, MD, rheumatologist in the Department of Pediatrics, University Medical Center Utrecht, Utrecht, Netherlands, and Marco Gattorno, MD, rheumatologist at the Center for Autoinflammatory Diseases and Immunodeficiency at IRCCS Instituto Giannina Gaslini, Genoa, Italy.

“It’s helpful to characterize this group of patients, because very little is known about these individuals and how to manage their disease,” says Dr. Frenkel. “Autoinflammatory diseases are disorders of uncontrolled, innate inflammatory activation. In many patients, there is a defined genetic cause, but in more the cause remains elusive.”

Results at a Glance
Among the 187 patients studied, seven patients had a chronic disease course and 180 patients had a recurrent disease course, with the median disease onset of 4.3 years. Common symptoms reported by study patients included arthralgia, myalgia, abdominal pain, fatigue, malaise and mucocutaneous manifestations. Relatives of 24 study patients were affected, and in 15 patients not pathogenic variants were found in genes associated to known autoinflammatory diseases.

Pericarditis was observed in a subgroup of 11 patients and had an average age of 33.8 years at disease onset, with fewer episodes—three per year—compared with other patients. Eight patients with intellectual impairment had an average age of 2.2 years at disease onset and 28.6% had affected relatives.

Shedding Light on Orphan Disorders
“The data summarized in our paper are just a starting point,” says Dr. Gattorno. “We are currently collecting data longitudinally. This will inform us about the natural history of this group, including response to treatment, which may be very useful in practical patient care.”