Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children.

BACKGROUND: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce. OBJECTIVE: To assess the effect of leflunomide on BKvirus in kidney-transplanted children. METHODS: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded. RESULTS: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis. CONCLUSION: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30-40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.

[Brain tuberculoma in a 10-year-old child: the diagnosis is in the belly]. / Tuberculome cérébral chez une enfant de 10 ans diagnostiqué par biopsie d'une adénopathie abdominale.

We report the case of a 10-year-old child from Reunion Island who was hospitalized because of headaches and partial convulsive fits. The brain MRI showed several conglomerated right frontal lesions suggestive of a tumor process. This girl, vaccinated with BCG, had familial risk factors for tuberculosis and a 20-mm tuberculin intradermo-reaction. Given the palpation of an abdominal mass, a thoracoabdominal scan was done, which revealed the presence of mesenteric adenopathies. Their biopsy confirmed the diagnosis of tuberculosis without having to perform neurosurgery. A 2-month quadritherapy and a 10-month dual therapy against tuberculosis led to the disappearance of brain damage and mesenteric adenopathies, with focal epilepsy the only sequela. The tuberculosis incidence in Reunion Island (8/100,000) is comparable with the French average, but the island is surrounded by high-endemic countries. Tuberculomas were responsible for one-third of expanding intracranial lesions in Europe in 1933, and their incidence remains high in developing countries. Even though extrapulmonary or disseminated tuberculosis has become rare in children in industrialized countries, this diagnosis must be kept in mind, in spite of vaccination. In accordance with international guidelines, this case report shows the importance of a systematic extensive check-up (cervical, thoracic and abdominopelvic) when brain tuberculosis is suspected in order to find more accessible tuberculosis lesions and to avoid the side effects of a brain biopsy.

[EBV infection revealing a long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in a 3-year-old boy]. / Infection à EBV révélatrice à l'âge de 3 ans d'un déficit en 3-hydroxyacyl-CoA déshydrogénase des acides gras à chaîne longue (LCHAD).

OBSERVATION: We report on the case of a 3-year-old child from La Réunion island, who presented with hypoglycemic hypoketotic coma secondary to a primary Epstein-Barr virus (EBV) infection. The discovery of the G1528C homozygote mutation provided the diagnosis of long-chain-3-hydroxyacyl-CoA-dehydrogenase (LCHAD); an adapted dietary plan with prevention of fasting and L-carnitine supplementation was initiated. After 2 years, a pigmentary retinopathy appeared and muscle weakness increased. COMMENTS: Isolated LCHAD deficiency is an autosomal recessive disorder of fatty acid metabolism. Prevalence is about 1-9/100,000 and diagnosis is often made before the age of 2 years. The late age of revelation in our case is related to a spontaneous diet without animal fats (disgust for meat, diet based on white rice and skimmed milk) and nighttime breastfeeding until the age of 3 years. In an affected fetus, heterozygous mothers are susceptible to developing a hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome or an acute fatty liver pregnancy (AFLP) syndrome during the 3rd trimester of pregnancy, which motivated us to set up a systematic neonatal screening program and a specific monitoring of these newborns.

[Familial cerebral cavernomas: discovery made during an epileptic seizure in a 10-year-old girl]. / Cavernome cérébral familial: révélation par une épilepsie chez une fille de 10 ans.

The assessment of an epileptic seizure in a 10-year-old girl originating from Reunion Island revealed a case of familial cerebral cavernous angioma. Multiple hemorrhagic lesions seen during a cerebral magnetic resonance imaging (MRI) scan was suggestive of cavernomas. A cerebral MRI scan in the father showed multiple asymptomatic lesions, thus confirming the familial nature. A genetic study carried out on the patient and her father confirmed the presence of a mutation of the KRIT1 gene with an autosomal dominant transmission. In these disorders, an MRI scan in the patient's parents offers great diagnostic advantages. This screening leads to precautionary measures that are easy to put in place.

[Lymphocytis meningitis: Listeria monocytogenes is a potential risk in a immunocompetent child]. / Méningite lymphocytaire: Listeria monocytogenes, une étiologie à ne pas négliger chez l'enfant immunocompétent.

UNLABELLED: Meningoencephalitis due to Listeria monocytogenes is a rare and serious form of brainstem infection in childhood. OBSERVATION: We report the case of a 7 year-old girl presenting lymphocytic meningitis with a high CRP level. Parenteral antibiotics combining ceftriaxone and vancomycine led initially to clinical improvement. Ten days later, secondary brainstem inflammation with hydrocephalus appeared and led to the detection of L. monocytogenes during external ventricular bypass. CONCLUSION: This observation of paediatric lymphocytic meningoencephalitis suggests a prescription of amoxicillin in association with first line antibiotics, particularly when an important inflammatory syndrome exists, immunocompetent children included.

[Maternal toxoplasmosis before conception and chorioretinitis in twin sisters]. / Toxoplasmose maternelle anté-conceptionnelle et choriorétinite chez des jumelles.

A maternal toxoplasmosis before conception is exceptionally transmitted to the fetus. We report an observation of twin sisters who presented congenital toxoplasmosis with chorioretinitis detected at nine months of age. The anamnesis revealed that the mother had had toxoplasmosis one month before conception. In the event of preconceptual infections, we propose fetal ultrasonography, histological examination of the placenta at delivery, as well as a pediatric follow-up of the infants (serological samples every month, cranial ultrasonography, fundus oculi).

[Clinical aspects and genetic specificities of cystic fibrosis in Reunion Island]. / Aspects cliniques et spécificités génétiques de la mucoviscidose à l'île de la Réunion.

OBJECTIVES: Evaluation of the phenotype-genotype correlation of a specific mucoviscidosis mutation, "Y122X", in Reunion Island. This mutation represents 25% of our cases. PATIENTS AND METHODS: Retrospective study of a cohort of 84 children presenting cystic fibrosis (CF) during a 5-year period (1994-1998). Diagnosis was based on one or two identified genetic mutations and/or minimum two abnormal chloride sweat tests (Cl > 70 mmol/l). Follow-up of this cohort was performed in the two referral centers of the Island following the French national guidelines (INSERM U 155). RESULTS: In our population, we identified 10 mutations, of which three of them represented more than 80% of the cases: Delta F508 (51.8%), Y122X (24.4%) and 3120 + 1G --> A (4.8%). The authors report clinical significant differences in children with the homozygote mutation Y122X as compared with children presenting the Delta F508 CF-mutation: failure to thrive affecting mainly the height with, paradoxically, a relatively normal weight development, and a better pulmonary function. CONCLUSION: The frequent Y122X CF-mutation reported in "la Reunion" seems to affect mainly height in children with a relatively good nutritional outcome. This failure to thrive does not seem to be of digestive origin. These results suggest that growth gene(s) located nearby the cystic fibrosis transmembrane conductance regulator (CFTR) may have suffered the same segregation than the Y122X mutation or that clusters of this specific Caucasian population known as "petits blancs" in la Reunion are smallest for ethnic reasons.