Supplementary Table S1 CAPS systematic literature review search strategy
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1 Supplementary Table S1 CAPS systematic literature review search strategy CAPS Pubmed CAPS Embase cryopyrin associated periodic syndromes [MeSH Terms] OR Cryopyrin Associated Periodic Syndromes [tiab] OR Cryopyrin Associated Periodic Syndrome [tiab] OR Cryopyrin Associated Periodic Fever Syndromes [tiab] OR Cryopyrin Associated Periodic Fever Syndrome [tiab OR cryopyrinopath*[tiab] OR FCAS[tiab] OR Familial Cold Autoinflammatory Syndrome [tiab] OR Familial Cold Urticaria [tiab] OR MWS[tiab] OR Muckle Wells Syndrome [tiab] OR CINCA[tiab] OR (Chronic[tiab] AND Infantile[tiab] AND Neurological[tiab] AND Cutaneous[tiab] AND Articular[tiab]) OR NOMID[tiab] OR Neonatal Onset Multisystem Inflammatory Disease [tiab] OR Infantile Onset Multisystem Inflammatory Disease [tiab] 'cinca syndrome'/exp OR 'muckle wells syndrome'/exp OR 'familial cold autoinflammatory syndrome'/exp OR 'cryopyrin associated periodic syndromes':ab,ti OR 'cryopyrin associated periodic syndrome':ab,ti OR 'cryopyrin associated periodic fever syndromes':ab,ti OR 'cryopyrin
2 CAPS associated periodic fever syndrome':ab,ti OR cryopyrinopath*:ab,ti OR fcas:ab,ti OR 'familial cold autoinflammatory syndrome':ab,ti OR 'familial cold urticaria':ab,ti OR mws:ab,ti OR 'muckle wells syndrome':ab,ti OR cinca:ab,ti OR (chronic:ab,ti AND infantile:ab,ti AND neurological:ab,ti AND cutaneous:ab,ti AND articular:ab,ti) OR nomid:ab,ti OR 'neonatal onset multisystem inflammatory disease':ab,ti OR 'infantile onset multisystem inflammatory disease':ab,ti MeSH descriptor: [Cryopyrin-Associated Periodic Syndromes] explode all trees OR "Cryopyrin Associated Periodic Syndromes" or "Cryopyrin Associated Periodic Syndrome" or "Cryopyrin Associated Periodic Fever Syndromes" or "Cryopyrin Associated Periodic Fever Syndrome or cryopyrinopath* or FCAS or "Familial Cold Autoinflammatory Syndrome" or "Familial Cold Urticaria" or MWS or "Muckle Wells Syndrome" or CINCA or (Chronic and Infantile and Neurological and Cutaneous and Articular) or NOMID or "Neonatal Onset Multisystem Inflammatory Disease" or "Infantile Onset Multisystem Inflammatory Disease"(title/abstract) 29
3 AID Pubmed AID Embase AID Cochrane Hereditary Autoinflammatory Diseases"[Mesh:NoExp] OR autoinflammatory diseases [tiab] OR autoinflammatory syndromes [tiab] OR periodic fever syndromes [tiab] OR autoinflammatory disease [tiab] OR autoinflammatory syndrome [tiab] OR periodic fever syndrome [tiab] 'autoinflammatory disease'/de OR 'hereditary periodic fever'/de OR 'autoinflammatory diseases':ab,ti OR 'autoinflammatory syndromes':ab,ti OR 'periodic fever syndromes':ab,ti OR 'autoinflammatory disease':ab,ti OR 'autoinflammatory syndrome':ab,ti OR 'periodic fever syndrome':ab,ti MeSH descriptor: [Hereditary Autoinflammatory Diseases] this term only OR "autoinflammatory diseases" or "autoinflammatory syndromes" or "periodic fever syndromes" or "autoinflammatory disease" or "autoinflammatory syndrome" or "periodic fever syndrome"(title/abstract) 781 (all) 253 (new) 1388 all 508 new 33
4 Supplementary Table S2 Questionnaire for Cryopyrin-Associated Periodic Syndrome (CAPS) expert survey Q1 Family History 1. A positive family history of a genetically confirmed diagnosis of Cryopyrin-Associated Periodic Syndrome (CAPS) in a family member 2. A positive family history of clinical signs and symptoms associated with CAPS Q2 Characteristic of active disease 1. Age at disease onset 2. Episodic nature of symptoms 3. Duration of episodes 4. External triggers resulting in disease flares a) Cold-induced flares b) Stress-induced flares c) Infection-induced flares Q3 Systemic clinical symptoms of active disease 1. Fever 2. Fatigue 3. Headaches 4. Irritability Q4 Organ-specific clinical symptoms of active disease 1. Eye manifestations a) Conjunctivitis b) Keratitis c) Uveitis d) Papilledema and/or secondary optic nerve damage (atrophy, vision loss) 2. Oral/ear-nose-throat (ENT) manifestations a) Oral ulcers or aphthous stomatitis b) Exudative pharyngitis c) Cervical lymphadenopathy d) Sensorineural hearing loss 3. Chest manifestations a) Pleuritis / pericarditis / chest pain
5 4. Abdominal manifestations a) Abdominal pain b) Splenomegaly c) Renal manifestations: proteinuria d) Renal manifestations: amyloidosis 5. Skin manifestations a) Urticaria-like rash b) Maculo-papular rash 6. Musculoskeletal manifestations a) Bone deformities (patella overgrowth, clubbing, frontal bossing) b) Growth retardation c) CNS manifestations 7. Meningitis headaches / aseptic meningitis 8. Other manifestations, please specify a) b) Please check each item in respect to relevance and applicability: Item #: RELEVANCE Not relevant Often not relevant Undecided Often relevant Very relevant Consider this variable APPLICABILITY This score applies to All diseases in the CAPS spectrum Only some diseases in the CAPS spectrum, please check all applicable FCAS FCAS/MWS overlap MWS MWS/CI NCA/NOMID overlap CI NCA/NOMID
6 Supplementary Table S3 Inertia and Chi-Square Decomposition of proposed diagnostic model for CAPS Legend: Multiple correspondence analysis (MCA) allows the optimal representation of a contingency table in low-dimensional space. The mathematical procedures involved in correspondence analysis can be found in Greenacre M J (1984)(13). The model was developed using 1000Minds PAPRIKA methodology and then applied to a validation dataset using MCA. The model was then refined and tested as described in the manuscript.
7 Supplementary Table S4 Contributions to the Total Chi-Square Statistic of Diagnosis versus CAPS signs and symptoms Table 4. Contributions to the Total Chi-Square Statistic of Diagnosis vs CAPS signs/symptoms Diagnosis symptoms onset infancy >2 episodes continuous fever/chills triggered symptoms /rigor episodes urticara aseptic conjunctivitis meningitis hearing loss MSK skeletal symptoms abnormalities amyloidosis raised inflam markers NLRP3 mutation CAPS FMF KD - Incomplete KD/ Typical Other Fever Syndrome Schnitzler SJIA Sum Sum
8 Supplementary Table S5 MCA Pearson s Residual of Diagnosis versus CAPS signs and symptoms Table 5. MCA Pearson s Residual of Diagnosis vs CAPS signs/symptoms Diagnosis symptoms onset infancy >2 episodes continuous fever/chills symptoms /rigor triggered episodes urticara aseptic meningitis conjunctivitis hearing loss MSK symptoms skeletal abnormalities amyloidosis raised inflam markers NLRP3 mutation CAPS FMF KD - Incomplete KD/ Typical Other Fever Syndrome Schnitzler SJIA
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