CRIA syndrome

CRIA is the acronym for “cleavage-resistant RIPK1-induced autoinflammatory syndrome/ CRIA syndrome and refers to a rare, monogenic autoinflammatory disorder characterized by recurrent episodes of fever—usually with early onset—and pronounced, intermittent lymph node swelling. Dermatologically, an association with Sweet’s syndrome has been described (Hernández Sánchez J et al. 2026).

The cause is heterozygous variants of the RIPK1 gene at the protein’s cleavage site, particularly at aspartic acid residue 324. Normally, caspase-8 limits the activity of RIPK1 by cleaving it. The altered kinase is resistant to this cleavage; as a result, inflammatory signaling pathways and processes of programmed cell death are excessively activated. The disorder can be inherited in an autosomal dominant manner or arise from a de novo variant. It must be distinguished from biallelic RIPK1 deficiency.

The main symptoms are periodic fever and recurrent lymphadenopathy. If clinically suspected, the diagnosis is supported by the identification of a disease-causing RIPK1 variant.

There is currently no generally accepted causal treatment. Clinical improvement has been reported with IL-6 receptor blockade; direct inhibition of RIPK1 kinase is a therapeutic research approach.

A 40-day-old female patient, who had previously been healthy and had no relevant family history, presented to the emergency department due to recurrent episodes of fever. Initial laboratory tests revealed leukocytosis, thrombocytosis, and a slightly elevated C-reactive protein level. The patient subsequently developed persistent fever and a micropapulopustular neutrophilic rash (Sweet’s syndrome). The initial diagnosis was a urinary tract infection caused by susceptible Escherichia coli, following which antibiotic therapy was initiated. After molecular genetic confirmation of the diagnosis (CRIA), successful treatment with Anakinra was initiated (Hernández Sánchez J et al. 2026).