Pattern and diagnostic evaluation of systemic autoinflammatory diseases other than familial Mediterranean fever among Arab children: a multicenter study from the Pediatric Rheumatology Arab Group (PRAG)
To define the spectrum and phenotypic characteristics of systemic autoinflammatory diseases (SAIDs) other than familial Mediterranean fever (FMF) in Arab children and to delineate diagnostic evaluation. Data retrospectively collected on patients with clinical and/or genetically proven SAIDs other than FMF at 10 tertiary Arab pediatric rheumatology clinics from 1990 to 2018. The collected data comprised the clinical findings and diagnostic evaluation including genetic testing, the provided treatment and the accrual damage related to SAIDs. A total of 144 patients (93 female) with a median age at onset of 2.5 (range 0.1–12) years were enrolled. The initial diagnosis was inaccurate in 49.3%. Consanguinity rate among parents was 74.6%. The median time-to-diagnosis for all SAIDs was 2.5 (range 0.1–10) years. There were 104 patients (72.2%) with a confirmed diagnosis and 40 patients with suspected SAIDs. Seventy-two had monogenic and 66 patients with multifactorial SAIDs while six patients had undifferentiated SAIDs. The most frequent monogenic SAIDs were LACC1 mediated monogenic disorders (n = 23) followed by CAPS (12), TRAPS (12), HIDS (12), and Majeed’s syndrome (6). The most frequent multifactorial SAIDs was CRMO (34), followed by PFAPA (18), and early onset sarcoidosis (EOS) (14). Genetic analysis was performed in 69 patients; 50 patients had genetically confirmed disease. Corticosteroid used for 93 patients while biologic agents for 96 patients. Overall, growth failure was the most frequent accrual damage (36%), followed by cognitive impairment (13%). There were three deaths because of infection. This study shows a heterogenous spectrum of SAIDs with a high number of genetically confirmed monogenic diseases; notably, LACC1 associated diseases. Hopefully, this work will be the first step for a prospective registry for SAIDs in Arab countries.
KeywordsAutoinflammatory diseases Familial mediterranean fever CAPS TRAPS LACC1 Arabs
This study was not funded by any agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Taking in consideration the nature of this retrospective work, informed consent for participation in this study was not required. However, an informed consent for genetic testing as part of patient care was obtained from patient or parent.
- 9.Mansour A, El-Shayeb A, El Habachi N, Khodair M, Elwazzan D, Abdeen N et al (2019) Molecular patterns of MEFV gene mutations in egyptian patients with familial mediterranean fever: a retrospective cohort study. Int J Inflam. https://doi.org/10.1155/2019/2578760(eCollection 2019) CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Chuamanochan M, Weller K, Feist E, Kallinich T, Maurer M, Kuemmerle-Deschner J et al (2019) State of care for patients with systemic autoinflammatory diseases—results of a tertiary care survey. World Allergy Organ J. https://doi.org/10.1016/j.waojou.2019.100019 CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Toplak N, Dolezalova P, Constantin T, Sediva A, Pasic S, Cinzar P et al (2010) Periodic fever syndromes in Eastern and Central European countries: results of a pediatric multinational survey. Pediatr Rheumatol Online J. https://doi.org/10.1186/1546-0096-8-29 CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Ozen S, Kuemmerle-Deschner J, Cimaz R, Livneth A, Quartier P, Kon-Paut I et al (2017) International retrospective chart review of treatment patterns in severe familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, and mevalonate kinase deficiency/hyperimmunoglobulinemia D syndrome. Arthritis Care Res (Hoboken) 69:578–586CrossRefGoogle Scholar