32^nd World Pediatrics Conference

Biography

Biography: Natalia Antonova

Abstract

The pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown. It is regarded as an autoinflammatory process. Disease onset is usually before the age of five and generally resolves before puberty with no consequences for the patient. Children are asymptomatic between episodes and show normal growth. No specific diagnostic test for PFAPA is currently available. Syndrome has overlapping symptoms with other periodic fever syndromes with a known genetic cause. Genomic analysis of familial cases by genome-wide linkage analysis and whole-exome sequencing did not reveal rare variants in a single, common gene. In addition, genetic variants that are known to cause other autoinflammatory syndromes have been found in PFAPA patients, but the impact of these genetic variants in PFAPA syndrome is still unknown.

A 2-year Caucasian/Azerbaijan girl demonstrated repeated fever episodes with high levels (90-200 mg/l) of C-reactive protein (CRP) since 6 mo. She was observed regularly because of microcephalus, slight developmental delay and growth retardation, muscle hypotonus and dysmorphic phenotype (broad forehead, hypertelorism, micrognathia, and retrognathia, fluffy eyebrows, long and tight eyelashes, long filtrum, narrow lips). On genetic consultation, she was diagnosed with 7p22 microdeletions. During a period of January-October 2018, she was hospitalized 6 times with high fever, cervical l/adenitis and sore throat (3 times with aphthous pharyngitis). Different laboratory tests and instrumental investigations were performed and were normal: abdomen ultrasound, chest X-ray, EKG and EHHOKG, ANA, HIV, Borreliosis serology and Quantiferron test, urine test, and urine culture. Cervical ultrasound revealed increased lymphoid nodules with normal structure. In a period of January-July of 2018, she received 4 antibiotic courses because of high CRP levels and pharyngitis. A blood test revealed no neutropenia, Sedimentation rate was always increased up to 20-40 mm/t, procalcitonin level and blood culture repeatedly negatives. Brain MRI with spectroscopy was performed to exclude intracranial pathology because of congenital problems. ENT repeated consultations excluded otitis media, but adenoid hypertrophy was considered.

PFAPA was suspected because of typical clinical symptoms (repeated episodes of fever with aphthous pharyngitis, cervical l/adenitis and high CRP levels, absence of neutropenia).  Prednisolone treatment 1 mg/kg per os was used twice with excellent effect. Adenotomy with tonsillectomy was performed in October 2018. After this treatment in a period of November 2018- May 2019 the patient was ill 4 times with no high fever (gastroenteritis, conjunctivitis, rhinopharyngitis and Varicella with otitis media ) and just once needed antibiotic treatment.

Sequencing of genes was performed to exclude MEFV, MVK, TNFRSF1A, IL1RN, and other gene abnormalities, using Illumina TruSightOne expanded panel (6700 genes). No monogenic fever syndrome was revealed.