Table 2

New Eurofever/PRINTO classification criteria for hereditary recurrent fevers and their performance in the 281 patients with consensus

CAPSFMFTRAPSMKD
Presence of a confirmatory NLRP3 genotype* and at least one among the following:

  • Urticarial rash.

  • Red eye (conjunctivitis, episcleritis, uveitis).

  • Neurosensorial hearing loss.


OR
Presence of not confirmatory NLRP3 genotype† and at least two among the following:

  • Urticarial rash.

  • Red eye (conjunctivitis, episcleritis, uveitis).

  • Neurosensorial hearing loss.

Presence of confirmatory MEFV genotype* and at least one among the following:

  • Duration of episodes 1–3 days.

  • Arthritis.

  • Chest pain.

  • Abdominal pain.


OR
Presence of not confirmatory MEFV genotype‡ and at least two among the following:

  • Duration of episodes 1–3 days.

  • Arthritis.

  • Chest pain.

  • Abdominal pain.

Presence of confirmatory TNFRSF1A genotype* and at least one among the following:

  • Duration of episodes ≥7 days.

  • Myalgia.

  • Migratory rash.

  • Periorbital oedema.

  • Relatives affected.


OR
Presence of a not confirmatory TNFRSF1A genotype† and at least two among the following:

  • Duration of episodes ≥7 days.

  • Myalgia.

  • Migratory rash.

  • Periorbital oedema.

  • Relatives affected.

Presence of a confirmatory MVK genotype* and at least one among the following:

  • Gastrointestinal symptoms.

  • Cervical lymphadenitis.

  • Aphthous stomatitis.

Sensitivity: 1Sensitivity: 0.94Sensitivity: 0.95Sensitivity: 0.98
Specificity: 1Specificity: 0.95Specificity: 0.99Specificity: 1
Accuracy: 1Accuracy: 0.98Accuracy: 0.99Accuracy: 1

  • A patient with (1) evidence of elevation of acute phase reactants (ESR or CRP or SAA) in correspondence to the clinical flares and (2) careful consideration of possible confounding diseases (neoplasms, infections, autoimmune conditions, other inborn errors of immunity) and a reasonable period of recurrent disease activity (at least 6 months) is classified as having hereditary recurrent fever if the criteria are met.

  • *Pathogenic or likely pathogenic variants (heterozygous in AD diseases, homozygous or in trans (or biallelic) compound heterozygous in AR diseases).

  • †Variant of uncertain significance (VUS). Benign and likely benign variants should be excluded.

  • ‡In trans compound heterozygous for one pathogenic MEFV variants and one VUS, or biallelic VUS, or heterozygous for one pathogenic MEFV variant. See online supplementary table 7 for glossary.

  • AD, autosomal dominant; AR, autosomal recessive; CAPS, cryopyrin-associated periodic syndromes; CRP, C-reactive protein; ESR, erythocytes sedimentation rate; FMF, familial Mediterranean fever; MKD, mevalonate kinase deficiency; MVK, mevalonate kinase; PRINTO, pediatric rheumatology international trial organization; SAA, serum amyloid A; TRAPS, tumour necrosis factor receptor-associated periodic fever syndrome.