The Added Value of a Multidisciplinary Clinic for Systemic Autoinflammatory Diseases

Figures & data

Table 1 Focus Areas of the CHLN-SAID Clinic

Focus Area
Principles for referral	● Establishment of criteria for referral
Infrastructure and technology	● Dedicated physical space where SAID patient appointments occur ● Electronic medical records used in this clinic: Reuma.pt/SAID allows the standardized collection of data for future research ● Reuma.pt/SAID includes disease activity assessment tools ● Quick access when requesting blood tests for diagnostic and follow-up purposes
Appointments	● Scheduled pediatric and adult SAID appointments ● Scheduled joint pediatrics-rheumatology appointments
Meetings	● Weekly dedicated bDMARD decision clinic ● Digital conference discussions whenever necessary
Organization of human resources	● The team is composed of two pediatric rheumatologists, two pediatricians specialized in infectious diseases and immunodeficiencies and one medical geneticist

Figure 1 Diagnoses of adult and pediatric patients with SAID followed at the CHLN-SAID clinic.

Abbreviations: uSAID, undefined systemic autoinflammatory disease; NLRP12, NLRP12-related autoinflammatory disease; HIDS/MKD, hyperimmunoglobulin D syndrome/mevalonate-kinase deficiency; CAMPS, CARD14-mediated psoriasis; DADA2, deficiency of adenosine deaminase 2; TRAPS, tumor necrosis factor receptor associated periodic syndrome; CAPS, cryopyrin associated periodic syndromes; FMF, familial Mediterranean fever; SAPHO, synovitis, acne, pustulosis, hyperostosis, osteitis syndrome; CNO, chronic recurrent multifocal osteomyelitis; PFAPA, periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome.

Table 2 Demographics, Clinical Manifestations, Diagnostic Test Findings and Treatment of the Patients Followed at the CHLN-SAID Clinic

	Monogenic Autoinflammatory Diseases							Multifactorial SAID			uSAID^a
	FMF n=5	HIDS/MKD n=2	CAPS n=2	TRAPS n=1	NLRP12-rAID n=1	CAMPSn=1	DADA2 n=1	PFAPA n=133	CNO n=6	SAPHOn=4	n=20
Demographics
Median age at onset, years [IQR]	12,4 [19,8]	4,6 [1,3]	3,9 [3,4]	1,1 [0]	0,7 [0]	0,1 [0]	5 [0]	2,6 [3]	12,5 [3,4]	35,8 [19,3]	3,8 [6,7]
Female (%)	2 (40)	1 (50)	2 (100)	0 (0)	0 (0)	0 (0)	1 (100)	58 (44)	1 (17)	1 (25)	8 (40)
Median time to diagnosis [IQR]	3,9 [8,1]	2,1 [1,2]	16,9 [5,4]	17,7 [0]	0,7 [0]	3,5 [0]	28 [0]	2,3 [2,6]	3,1 [3]	2,7 [2,5]	1,8 [1,7]
Time of follow-up (years)	0.7	1.7	6.3	0.6	0.6	3.1	9.6	2,5	3.5	0.0	1.5
Median number of visits [IQR]	1 [1]	3 [0]	15,5 [14,5]	3 [0]	3 [0]	2 [0]	71 [0]	4 [4]	3,5 [3,3]	1 [0]	2,5 [3,3]
Family history	2	2	0	1	0	0	0	72	1	0	9
Consanguinity	0	0	0	0	1	0	0	0	0	0	1
Ethnicity
White	2	2	1	1	1	1	1	111	5	0	15
Black	0	0	0	0	0	0	0	2	0	0	0
Asian	0	0	1	0	0	0	0	0	0	0	1
Unknown	3	0	0	0	0	0	0	20	1	4	4
Clinical manifestations
History of fever	2	2	1	1	0	0	1	133	1	0	18
Constitutional	0	0	1	0	0	0	1	7	0	0	6
Musculoskeletal	1	1	1	1	0	1	1	32	1	1	10
Arthralgia	1	0	0	1	0	1	1	12	1	0	10
Arthritis	0	0	1	0	0	1	1	0	0	1	0
Myalgia	0	1	0	0	0	0	0	21	1	0	2
Mucous membranes	0	1	0	0	0	0	0	91	1	0	3
Cutaneous	0	1	1	0	1	1	1	4	1	1	5
Ocular	0	0	1	1	0	0	0	1	0	0	1
Ear, nose, and throat symptoms	0	2	0	0	0	0	0	119	1	0	4
Cardiorespiratory	1	0	0	0	1	0	0	1	0	0	2
Neurological	0	0	0	1	0	0	1	25	0	0	4
Reticuloendothelial system	0	1	0	1	0	1	0	89	0	0	4
Sensorineural hearing loss	0	0	0	0	0	0	0	0	0	0	1
Gastrointestinal	2	1	0	1	0	0	0	56	1	0	6
Failure to thrive	0	0	0	0	0	0	1	2	0	0	0
Follow-up
Lost to follow-up	1	0	0	0	0	0	0	45	0	0	1
Remission	0	0	0	0	0	0	0	32	3	0	1
Diagnostic test findings
Positive genetic testing	4/4	1/2	1/2	1/1	1/1	1/1	1/1	0/12	0/0	0/0	0/8
Gene and mutations found	MEFV (M694V)	MVK (V377I and C152Y)	NLRP3 (E304K)	TNFRSF1A (p.R92Q)	NLRP12	CARD14	ADA2 (G47R and Y453C)
Treatment
Glucocorticoids^b	0	2	0	0	1	0	1	118	3	0	9
sDMARDs
Azathioprine	0	0	0	0	0	0	0	0	0	0	2
Cyclosporine	0	0	0	0	1	0	0	0	0	0	0
Hydroxychloroquine	0	0	0	0	0	0	0	0	0	0	0
Methotrexate	0	0	1^c	0	0	0	0	0	1	0	0
bDMARDs
Etanercept	0	0	0	1	0	0	0	0	0	0	0
Secukinumab	0	0	0	0	0	1	0	0	0	0	0
Infliximab	0	0	0	0	0	0	1	0	0	0	0
Canakinumab	0	1	1^c	0	0	0	0	0	0	0	1
Bisphosphonates	0	0	0	0	0	0	0	0	3	0	0
Colchicine	3	0	0	0	0	0	0	1	1	0	3
Tonsillectomy/adenoidectomy	0	0	0	0	0	0	0	26	0	0	2

Notes: This table only shows SAIDs for which there were registered patients. ^aPatients with clinical manifestations consistent with SAID after exclusion of either (1) other defined inflammatory conditions (ie rheumatic diseases, inflammatory bowel diseases) or other mimicking conditions (ie hematological diseases, tumors, immune deficiencies) and (2) defined autoinflammatory diseases. ^bGlucocorticoids used include Prednisolone, Deflazacort and Betamethasone. ^cThese treatments were used in the CINCA patients.

Abbreviations: FMF, familial Mediterranean fever; HIDS/MKD, hyperimmunoglobulin D syndrome/mevalonate-kinase deficiency; CAPS, cryopyrin associated periodic syndromes; TRAPS, tumor necrosis factor receptor associated periodic syndrome; NLRP12-rAID, NLRP12-related autoinflammatory disease; CAMPS, CARD14-mediated psoriasis; DADA2, deficiency of adenosine deaminase 2; PFAPA, periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome; CNO, chronic non-bacterial osteomyelitis; SAPHO, synovitis, acne, pustulosis, hyperostosis, osteitis syndrome; uSAID, undefined systemic autoinflammatory disease; MEFV, Mediterranean fever gene; MVK, mevalonate-kinase gene; NLRP3, NOD-like receptor 3 gene; TNFRSF1A, tumor necrosis factor receptor superfamily member 1A gene; NLRP12, NOD-like receptor 12 gene; ADA2, adenosine deaminase 2 gene; CARD14, caspase recruitment domain-containing protein 14 gene; sDMARDs synthetic disease-modifying antirheumatic drugs; bDMARDs, biological disease-modifying antirheumatic drugs.