Table 1

Overarching principles for the diagnosis, treatment and monitoring of CAPS, TRAPS, MKD and DIRA

	Overarching principles	LoE	GoR	LoA (0–10) mean±SD
A	Patients with the IL-1 mediated diseases CAPS, TRAPS, MKD and DIRA present with chronic or intermittent flares of systemic and organ inflammation that, if untreated, result in progressive organ damage, morbidity and increased mortality. A multidisciplinary team is required to diagnostically evaluate and manage patients with CAPS, TRAPS, MKD and DIRA, which includes evaluation of systemic inflammation, disease-associated complications and long-term treatment and management.	5	D	9.5±0.7
B	Patients presenting with chronic or episodic flares of unexplained systemic inflammation (including elevations of CRP and ESR) and clinical features suggestive of CAPS, TRAPS, MKD and DIRA should receive a prompt diagnostic workup comprising: genetic testing clinical workup focusing on the extent of inflammatory organ involvement screening for disease and treatment-related comorbidities	5	D	9.8±0.6
C	A genetic diagnosis for CAPS, TRAPS, MKD and DIRA is required which facilitates initiation of targeted treatments, genetic counselling, and informs prognosis. Genetic testing using a next-generation sequencing (NGS) platform should be used to diagnose CAPS, TRAPS, MKD and DIRA.	4	C	8.9±1.6
D	The goal of treatment is to control clinical signs and symptoms and normalise laboratory biomarkers of systemic inflammation using a treat-to-target approach.	5	D	9.6±0.8
E	Long-term monitoring goals should focus on: adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations fostering of self-management skills and medical decision-making initiating a transition programme to adult specialist care in adolescent patients	5	D	9.6±0.9

Level of evidence (LoE): 1a: systematic review of randomised controlled trials (RCTs); 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (including low-quality RCT); 3a: systematic review of case–control studies; 3b: individual case–control study; 4: case-series (and poor-quality cohort and case–control studies); 5: expert opinion without explicit critical appraisal, or based on physiology, bench research or ‘first principles’; Grade of recommendation (GoR): A: based on consistent level 1 studies; B: based on consistent level 2 or 3 studies or extrapolations from level 1 studies; C: based on level 4 studies or extrapolations from level 2 or 3 studies; D: based on level 5 studies or on troublingly inconsistent or inconclusive studies of any level.
CAPS, cryopyrin-associated periodic syndromes; CRP, C-reactive protein; DIRA, deficiency of the interleukin-1 receptor antagonist; ESR, erythrocyte sedimentation rate; LoA, level of agreement; MKD, mevalonate kinase deficiency; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.