Table 3.

Comparison of characteristics of RIPK1-associated diseases and similar autoinflammatory diseases. ^# 1/4 weeks denotes 1 episode every 4 weeks. Abbreviations: RIPK1, receptor-interacting serine/threonine kinase-1; CRIA, cleavage-resistant RIPK1-induced autoinflammatory syndrome; HIDS, hyper-IgD with periodic fever syndrome; PFAPA, periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome; CNS, central nervous system; MAS, macrophage activation syndrome; APR, acute phase reactants; n.r., not reported

	RIPK1 deficiency [7–10] (n: 14)	CRIA [11, 12] (n: 12)	HIDS [19] (n: 114)	PFAPA [20] (n: 301)	Caspase 8 deficiency [21–23] (n: 5)
Inheritance	Recessive	Dominant	Recessive	Unknown	Recessive
Gene	RIPK1	RIPK1	MVK	None	CASP8
Disease onset < 5 years (%)	100%	100%	100%	90%	20%
Disease pattern	Continuous	Periodic	Recurrent (87%)	Periodic	Continuous
Fever (duration)	n.r.	3–5 days	4 days	4 days	Reported in 1 patient
Fever (recurrence)#	n.r.	1/1–4 weeks	1/4 weeks	1/4 weeks	Reported in 1 patient
Episodes triggering factors	n.r.	n.r.	45%	n.r.	n.r.
Recurrent infections	100% (Severe)	n.r.	n.r.	n.r.	100% (Severe)
IBD/abdominal pain/diarrhea	100% / n.r. / n.r.	0% / 41.7% / n.r.	Occasional / 88% / 84%	n.r. / 45% / 16%	n.r. / 40% / 40%
Oral ulcers	46%	71.4%	60%	57%	n.r.
Pharyngitis	n.r.	42.9%	28%	90%	n.r.
Arthralgias	n.r.	37.5%	71%	30%	n.r.
Arthritis	38%	n.r.	28%	3%	n.r.
Skin rash	21%	n.r.	54%	13%	40%
CNS manifestations	7%	Headache	Headache (38%)	4%	20%
Conjunctivitis	n.r.	n.r.	10%	5%	n.r.
Uveitis	n.r.	n.r.	2%	n.r.	n.r.
Lymphadenopathies	n.r.	91.7%	89%	78%	60%
Splenomegaly	31%	58.3%	n.r.	n.r.	80%
Asthma	n.r.	n.r.	n.r.	n.r.	40%
Chronic lung disease	7.1%	n.r.	n.r.	n.r.	60%
AA amyloidosis	n.r.	n.r.	4%	n.r.	n.r.
MAS	n.r.	n.r.	0.9%	n.r.	n.r.
Outcome	High mortality (46%)	Overall good (100%)	Occasional life-threatening complications	Overall good (100%)	High mortality (40%)