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)

Rheumatol Int. 2020 Jan;40(1):49-56. doi: 10.1007/s00296-019-04478-3. Epub 2019 Nov 18.

Abstract

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.

Keywords: Arabs; Autoinflammatory diseases; CAPS; Familial mediterranean fever; LACC1; TRAPS.

Publication types

  • Multicenter Study

MeSH terms

  • Acne Vulgaris / diagnosis
  • Acne Vulgaris / drug therapy
  • Acne Vulgaris / epidemiology
  • Acne Vulgaris / physiopathology
  • Adolescent
  • Anemia, Dyserythropoietic, Congenital / diagnosis
  • Anemia, Dyserythropoietic, Congenital / drug therapy
  • Anemia, Dyserythropoietic, Congenital / epidemiology
  • Anemia, Dyserythropoietic, Congenital / physiopathology
  • Antirheumatic Agents / therapeutic use
  • Arabs
  • Arthritis / diagnosis
  • Arthritis / drug therapy
  • Arthritis / epidemiology
  • Arthritis / physiopathology
  • Arthritis, Infectious / diagnosis
  • Arthritis, Infectious / drug therapy
  • Arthritis, Infectious / epidemiology
  • Arthritis, Infectious / physiopathology
  • Arthritis, Juvenile / drug therapy
  • Arthritis, Juvenile / epidemiology
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / physiopathology
  • Bahrain / epidemiology
  • Child
  • Child, Preschool
  • Consanguinity
  • Crohn Disease / drug therapy
  • Crohn Disease / epidemiology
  • Crohn Disease / genetics
  • Crohn Disease / physiopathology
  • Cross-Sectional Studies
  • Cryopyrin-Associated Periodic Syndromes / diagnosis
  • Cryopyrin-Associated Periodic Syndromes / drug therapy
  • Cryopyrin-Associated Periodic Syndromes / epidemiology
  • Cryopyrin-Associated Periodic Syndromes / physiopathology
  • Diagnostic Errors
  • Female
  • Fever / diagnosis
  • Fever / drug therapy
  • Fever / epidemiology
  • Fever / physiopathology
  • Hereditary Autoinflammatory Diseases / diagnosis*
  • Hereditary Autoinflammatory Diseases / drug therapy
  • Hereditary Autoinflammatory Diseases / epidemiology*
  • Hereditary Autoinflammatory Diseases / physiopathology
  • Humans
  • Immunologic Deficiency Syndromes / diagnosis
  • Immunologic Deficiency Syndromes / drug therapy
  • Immunologic Deficiency Syndromes / epidemiology
  • Immunologic Deficiency Syndromes / physiopathology
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics
  • Jordan / epidemiology
  • Kuwait / epidemiology
  • Libya / epidemiology
  • Male
  • Mevalonate Kinase Deficiency / diagnosis
  • Mevalonate Kinase Deficiency / drug therapy
  • Mevalonate Kinase Deficiency / epidemiology
  • Mevalonate Kinase Deficiency / physiopathology
  • Oman / epidemiology
  • Osteomyelitis / diagnosis
  • Osteomyelitis / drug therapy
  • Osteomyelitis / epidemiology
  • Osteomyelitis / physiopathology
  • Pyoderma Gangrenosum / diagnosis
  • Pyoderma Gangrenosum / drug therapy
  • Pyoderma Gangrenosum / epidemiology
  • Pyoderma Gangrenosum / physiopathology
  • Retrospective Studies
  • Sarcoidosis / diagnosis
  • Sarcoidosis / drug therapy
  • Sarcoidosis / epidemiology
  • Sarcoidosis / physiopathology
  • Saudi Arabia / epidemiology
  • Synovitis / diagnosis
  • Synovitis / drug therapy
  • Synovitis / epidemiology
  • Synovitis / physiopathology
  • United Arab Emirates / epidemiology
  • Uveitis / diagnosis
  • Uveitis / drug therapy
  • Uveitis / epidemiology
  • Uveitis / physiopathology

Substances

  • Antirheumatic Agents
  • Intracellular Signaling Peptides and Proteins
  • LACC1 protein, human

Supplementary concepts

  • Blau syndrome
  • Chronic recurrent multifocal osteomyelitis
  • Majeed syndrome
  • Pediatric Crohn's disease
  • Periodic fever, familial, autosomal dominant
  • Pyogenic arthritis, pyoderma gangrenosum, and acne
  • chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature