O007. Register of hereditary auto-inflammatory diseases in a pediatric rheumatology unit
Authors: Souali M , Semlali F , Benbrahim G , Sakhi A , Mikou N , Bouayed K 
Published: November 2021

Abstract

Background
Autoinflammatory diseases (AID) are a group of genetic syndromes resulting from an excessive activation of the innate immune system, caused by mutations in genes regulating the inflammatory pathways and can involve several organs. The aim of this study is to evaluate the clinical, paraclinical, epidemiogical and genetic data of Moroccan patients with confirmed AID, in order to allow a first experience of AID registry in our unit.

Material
We have retrospectively analyzed 30 cases of patients in our unit over a period of 13 years (between 2006 and 2019), according to inclusion criterias (recurrent fever &gt; 3 episodes and a CRP &gt; 40mg/L) and having excluded immune deficiency, autoimmune disease, neoplasia and infectious diseases.

Results
The mean age of our patients at 1st consultation was 6.9 years (with extremes ranging from 8 months to 14 years). Consanguinity was reported in 16 cases, and unknown in one case of an adopted child. The patients were classified as follows: 66% of cases with Familial Mediterranean Fever (FMF) including 1 case with a characteristic phenotype of Marshall/Periodic Fever Aphtous Pharyngitis Adenitis (PFAPA) syndrome, 16% of cases with Mevalonate Kinase Deficiency (MKD), 10% of cases with Chronic Recurrent Multifocal Osteomyelitis (CRMO), 1 patient with Familial Pustular Psoriasis (FPP) and another symptomatic patient with Muckle Wells syndrome. An association with Henoch Schonlein purpura was reported in 30% of cases and with periarteritis nodosa in 1 case in FMF patients. The mean diagnostic delay was 3 years (with extremes ranging from 1 month to 12 years). The main clinical features found in our patients included fever (83%), abdominal pain (90%), arthralgia (83%), arthritis (46%), adenopathies (40%), aphtous (30%) and other specific signs. Genetic analysis revealed that M694V was the most frequent mutation (60%), followed by A744S (15%), E148Q (10%), K695R (10%) and P369S/ R408Q (5%) in all FMF patients, and V337I found in 1 patient with MKD while the 4 others were confirmed basing on a high rate of urinary mevalonic acid. CRMO patients were confirmed by radiological and histological analysis. The case of FPP was confirmed histologically by skin biopsy and the patients with Muckle Wells and PFAPA syndroms were diagnosed basing on characteristic clinical features. Therapeutically, all FMF patients were treated with colchicine in addition of corticosteroids in 1 case of PFAPA syndrome. Patients with MKD received targeted therapy (Anakinra, Etanercept) and Ibuprofen in 1 case. CRMO patients were treated with targeted therapy and NSAIDs. The case of FPP was treated with Methotrexate combined with Etanercept and the patient with Muckel Wells Syndrome received corticosteroid therapy combined with Azathioprine and then Anakinra. The clinical and biological evolution was considered favorable in 76% of cases, partial in 13% of cases and 3 death cases were reported.

Conclusion
AIDs remain rare genetic syndromes whose lack of knowledge explains the late diagnostic delay. Therefore, it is necessary for any pediatrician to know how to evoke an AID in front of recurrent fever with free intervals, clinical features and inflammatory syndrome, in order to choose the optimal treatment as well as to make the genetic counseling.

Abbreviations
AID: Auto-Inflammatory Disease
CAPS: Cryopyrin Associated Periodic Syndromes
CARD14: Caspase Recruitment Domain Family Member 14
CIAS1: Cold-Induced Autoinflammatory Syndrome 1
CRMO: Chronic Recurrent Multifocal Osteomyelitis
CRP: C-Reactive Protein
CT scan: Computerized Tomography scan
DNA: DeoxyriboNucleic Acid
ESR: Erythrocyte Sedimentation Rate
FMF: Familial Mediterranean Fever
FPP: Familial Pustular Psoriasis
IL-1β: Interleukine-1beta
IL-17A: Interleukine 17A
MEFV: Mediterranean fever gene
MKD: Mevalonate Kinase Deficiency
MVK: Mevalonate Kinase
MW: Muckle Wells
NALP3: NAcht Leucine-rich repeat Protein 3
NLRP3: NOD-like receptor family, pyrin domain containing 3
NSAID: Non-Steroidal Anti Inflammatory Drugs
PFAPA: Periodic Fever Aphtous Pharyngitis Adenitis
PRINTO: Pediatric Rheumatology INternational Trials Organization
SAA: Serum Amyloid A
TRAPS: TNF Receptor Associated Periodic Syndroms
TNF: Tumor Necrosis Factor