The challenging management of a series of 43 infants with Netherton syndrome: unexpected complications and novel mutations.

BACKGROUND: Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging. OBJECTIVES: To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management. METHODS: We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data. RESULTS: A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion. CONCLUSIONS: Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life-threatening manifestations of NS in neonates based on our multidisciplinary experience.

Severe atypical Lemierre syndrome caused by methicillin-sensitive Staphylococcus aureus: Two pediatric case reports.

BACKGROUND: Lemierre syndrome is typically associated with ear, nose, and throat (ENT) infections caused by Fusobacterium necrophorum. Since 2002, cases of atypical Lemierre-like syndrome secondary to Staphylococcus aureus have been reported. CASES: We report two pediatric cases of atypical Lemierre syndrome with a similar presentation: exophthalmia, absence of pharyngitis, metastatic lung infection, and intracranial venous sinus thrombosis. Both patients had a favorable outcome following treatment with antibiotics, anticoagulation, and corticosteroids. CONCLUSION: Regular therapeutic monitoring of antibiotic levels helped to optimize antimicrobial treatment in both cases.

Infant botulism: Report of a misleading case and important key messages.

Infant botulism is a rare and life-threatening disease caused by the inhalation of Clostridium botulinum spores and differs from adult forms. We report the case of infant botulism in a 4-month-old boy who was exclusively breastfed without any consumption of honey. He presented with severe and acute encephalo-myelo-radiculitis. The patient was treated without success for suspected "postviral" central nervous system inflammatory disease. The diagnosis was eventually made 20 days after the onset of symptoms on the basis of a stool sample. Recovery was complete. Infant botulism should be suspected when infants present with acute flaccid paralysis or brainstem weakness and specific immunoglobulins should be administered.

Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

[Should yellow fever vaccination be recommended during pregnancy or breastfeeding?]. / Vaccin amaril au cours de la grossesse ou de l'allaitement: que conseiller?

Yellow fever vaccine is produced from a live attenuated virus that is contraindicated in case of immunodeficiency and subject to restrictions for pregnant or breastfeeding women. The purpose of this review of available information on yellow fever vaccination during pregnancy and breastfeeding is to assist physicians in making recommendations prior to departure to yellow-fever endemic zones. Regarding pregnancy, there is no evidence to support a major risk of yellow-fever-vaccine-related complications in mothers or children. Although this finding is reassuring, it should be underlined that most reported series have been small. Regarding breastfeeding, the risk was recently confirmed by a report describing vaccine-induced encephalitis occurring in an infant 8 days after primary vaccination of the mother. The final decision to vaccinate depends on whether or not the trip can be postponed. If travel is mandatory, vaccination may be recommended in pregnant women preferably during the first trimester since the immunological response appears to be better at that time. Antibody titer should be checked following delivery. During breastfeeding, vaccination may be performed but breastfeeding must be stopped during the postvaccinal viremia phase. Breastfeeding can be resumed after a 10-day period of formula feeding.

Severe and fatal forms of COVID-19 in children.

OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.

[Managing children skin and soft tissue infections]. / Propositions thérapeutiques pour le traitement des infections cutanées bactériennes.

The skin infections are common in pediatrics, ranging from furonculosis or impetigo to the severe forms of necrotizing dermohypodermitis. The general antibiotic treatments are not always indicated but when they are, they must take into account the resistance of two main species of bacteria (Staphylococcus aureus and Streptococcus pyogenes), the pharmacokinetics-pharmacodynamic parameters and the severity and type of infection. Two situations should be treated by topical treatements: limited impetigo and furonculosis. The two topical antibiotics used preferentially are mupirocine and fucidic acid. Soon, a third topical antibiotic, reptamuline will complete these. For uncomplicated superficial skin infections justifying an oral antibiotic, amoxicillin-clavulanate offers the best guarantee of efficiency. Poor pharmacodynamic-pharmacokinetic must lead to not prescribe oral M penicillins. In case of allergy, a first-generation cephalosporin, a macrolide (if the susceptibility of the strain was checked) or pristinamycine (after 6 years of age) are acceptable alternatives. For dermohypodermitis bacterial antibiotic of choice remains amoxicillin-clavulanate through IV route, to be active against S. pyogenes but also S. aureus and anaerobic bacteria. The IV route is maintained until regression general signs and a relay orally by the same drug is then possible. For toxinic syndromes and necrozing fascitis clindamycin should be added to a beta-lactam because of its action on protein synthesis in particular reducing the toxins production.

[Systematic family screening in case of infant pertussis]. / Dépistage familial systématique dans la coqueluche du nourrisson.

The origin of contamination in pertussis of young infants is generally the close relatives. From 2000 to 2004, only serology and culture were available in our hospital. The families of 16 young infants (age below one year) hospitalized for pertussis were screened using serological tests: 21/48 contacts were positive. After 2004, PCR was available for exploration of index cases and families: 35/85 contacts were positive. Of the mothers tested 23/46 were positive compared to 14/41 fathers. Only one parent presented with a typical paroxystic pertussis cough, 60% presented with a nonparoxystic cough having lasted for more than five days and 40% of positive adults did not present with cough. Despite official recommendations, none of these young parents had received an antipertussis booster vaccination. This study shows the high frequency of atypical or nonsymptomatic pertussis in adults in the close family of infected young infants. These adults contribute to spreading the disease.

Pertussis in young infants: apnoea and intra-familial infection.

This study investigated 41 infants, aged <4 months, who were hospitalised with symptoms compatible with pertussis. Of these, 16 had Bordetella pertussis infection confirmed by real-time PCR. For four of these 16 patients, the initial sample was PCR-negative, but samples collected 5-7 days after the onset of infection were PCR-positive. PCR was also positive with samples from 15/16 families and 20/41 household contacts. Nine of the 20 positive household contacts were asymptomatic. Among the 16 infants with proven pertussis, apnoea was more frequent than in a control group for whom PCR was negative with both children and household contacts (69% vs. 28%). It was concluded that real-time PCR performed with samples from household contacts facilitates the diagnosis of infants suspected clinically of having pertussis, thereby enabling earlier treatment.

[Long-term clinical benefits of using active stents in diabetic patients: two year follow-up of a consecutive series of 122 patients]. / Bénéfice clinique à long terme de l'utilisation des stents actifs chez les patients diabétiques: suivi à deux ans d'une série consécutive de 122 patients.

The objective of our study is to evaluate the long-term results of coronary angioplasty using active stents in a population of diabetic patients. This is a single-centre study on a consecutive series of 122 diabetic patients (40% of them insulin dependent) who between January 2003 and June 2004 underwent angioplasty with implantation of an active stent (sirolimus Cypher(R) or paclitaxel Taxus(R)) for one or more de novo coronary lesions. The mean age was 66 +/- 10 years and a total of 171 coronary segments were treated. The lesions treated were complex (type B2 + C) in 69% of the cases, with a mean stent length of 21 +/- 15 mm and a mean stent diameter of 2.7 +/- 0.3 mm. Follow-up at two years for 119 patients (3 lost to follow-up) revealed a mortality rate of 4.2%, and a myocardial infarction rate of 7.5%. The rates for revascularisation of the target lesion and the target vessel were 11.4% and 17.8% respectively, with a rate of major cardiac events of 22.5%. During this period, 25.2% of the patients underwent revascularisation of at least one vessel. This study confirms the benefits of using active stents for revascularisation of the target lesion in diabetic patients. However, it serves as a reminder that the progression of coronary atheroma is global, and that the prognosis for these patients depends essentially upon managing risk factors, and particularly on controlling their diabetes.

[Distinction between bacterial and aseptic meningitis in children: refinement of a clinical decision rule]. / Distinction entre les méningites bactériennes et virales chez l'enfant: affinement d'une règle de décision clinique.

OBJECTIVES: To refine and to re-validate the best current tool (the Nigrovic rule: ''outpatient management may be considered for children without seizure, blood neutrophil count>or=10,000/mm(3), positive cerebrospinal fluid -CSF- Gram-staining, CSF protein>or=80 mg/dl, or CSF neutrophil count>or=1,000/mm(3)'') proposed to distinguish between aseptic meningitis (AM) and bacterial meningitis (BM) in the emergency department. METHODS: Children hospitalized for BM between 1995 and 2004, or AM between 2000 and 2004 were included, and randomly divided into derivation (111 children, 14 BM) and internal validation (57 children, 7 BM) sets. The Nigrovic rule was refined on the derivation set, introducing new variables (purpura, toxic appearance and high serum procalcitonin), changing variables thresholds (CSF protein) and withdrawing some variables (blood neutrophil count, CSF neutrophil count), according to previous results, with the aim to obtain 100% sensitivity user friendly tool. The refined rule was then applied on the internal validation set, stayed blinded during the derivation process. RESULTS: The refined rule was: start antibiotics in case of seizure, purpura, toxic appearance, procalcitonin>or=0.5 ng/ml, positive CSF Gram-staining, or CSF protein>or=50 mg/dl. The refined rule had 100% sensitivity on the derivation and the internal validation sets (95% confidence interval 78-100, and 65-100, respectively) with 62 and 51% specificity, respectively. CONCLUSION: The refined rule (called Meningitest) was a highly sensitive, specific and user friendly tool that could allow to safely avoid>50% a posteriori unuseful antibiotic treatments for patients with AM.

[Benefit of hip ultrasound in management of the limping child]. / Apport de l'échographie de hanche dans les boiteries de l'enfant.

OBJECTIVE: To evaluate the contribution of sonography of the hip in the management of nontraumatic limping in children. PATIENTS AND METHODS: Prospective study including children consulting for nontraumatic limping (n=93). These children had a clinical examination, a biological and imaging workup (pelvis x-rays (n=88), initial sonograph of the hip (n=93), and follow-up sonograph of the hip (n=29)). RESULTS: Ninety-three children (69 boys, 24 girls) aged from 10 months to 13 years (median, 4 years) were included and divided into two groups: The sensitivity and specificity of sonography in establishing a serious diagnosis was 57% and 59%, respectively. CONCLUSION: The advantage of systematic hip sonography is challenged in this study because of low sensitivity and specificity. Its main advantage seems to be in its negative results, which prompt other investigations.

[Mycotic coronary aneurysm with Escherichia coli sepsis: a case report]. / Anévrisme coronaire mycotique consécutif à une septicémie à Escherichia coli: à propos d'un cas.

We report the case of a patient who was admitted for acute coronary syndrom associated with fever originating from urinary tract. Coronary arteriography revealed a huge coronary aneurysm which ruptured a short time after diagnosis. After surgery, it was proven to be mycotic aneurysm related to Escherichia Coli sepsis.

[Simultaneous outbreaks of rotavirus and respiratory syncytial virus in Paris: a 12-year survey]. / Coïncidence des épidémies de rotavirus et de virus respiratoire syncytial à Paris: 12 ans de surveillance.

OBJECTIVE: The authors had for aim to study the coincidence of RSV and rotavirus epidemic peaks in pediatric patients hospitalized in the Paris area. METHODOLOGY: A retrospective hospital-based monocentric cohort study was made over a 12-year period (1993-2004). Clinical and laboratory findings were prospectively collected on admission. RESULTS: Three thousand and four hundred ninety-six stool samples were positive for rotavirus; 3,507 nasopharyngeal aspirates were positive for RSV. The coincidence of epidemic peaks for both viruses in November, December, and January was observed during the 12 years of the study. CONCLUSION: The exact coincidence of winter outbreaks of RSV and rotavirus is a characteristic of the Paris area. It contributes to increase overcrowding in pediatric units and nosocomial infections.

[Children tuberculosis after familial contamination: experience in general pediatrics]. / Tuberculose de l'enfant après contage familial: une expérience en pédiatrie générale.

UNLABELLED: The heterogeneity of clinical presentations of children in contact with a tuberculous adult do not allow simple guidelines for treatment and exams. Indications of thoracic computed tomography (CT) in young children and the risk of a follow-up without antituberculous treatment are always discussed. PATIENTS: Sixty-nine children, belonging to 50 families, living in close contact with an adult treated for tuberculosis were explored during 7 years in a General Pediatric Unit. A CT was performed in 51 patients. RESULTS: Mantoux test was negative in 3/17 children with typical tuberculous disease on X-ray. When results of CT were compared with those of standard thoracic X-ray, a difference for the diagnosis of mediastinal adenopathies was found only in children younger than 5 years. Fifty-eight patients were given usual treatment of latent or patent tuberculosis if indicated, or a chemoprophylaxis. All of them had normal clinical and X-ray exam 2 to 4 years later. Eleven children, initially checked in an other unit, were given no treatment, but a follow-up was set up. However, after 6 to 24 months, 4/11 had a patent tuberculosis and 5/11 a latent tuberculosis, 6/9 being aged more than 3 years. CONCLUSION: This study shows that risk of tuberculosis after familial contamination is high, and that the choice of absence of treatment with following re-evaluation, is sometimes questionable because families or doctors do not perform the prescribed follow-up. To perform systematically a thoracic CT, searching for mediastinal adenopathies, is useful only before the age of 5 years.

[Evaluation of pre-travel prevention and morbidity in child travelers]. / Enquêtes auprès des familles d'enfants voyageurs : évaluation des conseils de prévention et prévalence des maladies rencontrées lors d'un séjour hors d'Europe.

UNLABELLED: International travel is growing, but few data exist on prevention for children traveling. The aim of this study was to describe a population of children traveling from France to countries outside Europe and to evaluate the quality of prevention and healthcare services provided for these travelers. MATERIALS AND METHODS: We conducted a retrospective epidemiological study in three pediatric emergency departments in Paris from August to October 2009 and 2012. Data were collected retrospectively from anonymous questionnaires proposed to families consulting emergency services, irrespective of their reason, who had recently traveled (in the year preceding travel outside the European Union). RESULTS: Of the 166 children included, who for the most part had traveled to visit relatives and friends in Sub-Saharan Africa and North Africa, 76% of their families were from the destination countries, 78% had received prevention counseling, mostly with their doctor. They had been vaccinated against yellow fever, but the hepatitis A vaccine was neglected. The preventive measures had been difficult to achieve in practice. During travel, 54% of children had health problems (39% diarrhea, 29% vomiting, 31% fever) prompting medical care in 28%, 5% were admitted to a hospital, and 4% had return to France earlier than planned. In epidemic areas, 13% of children had malaria. CONCLUSION: There is poor counseling on basic prevention (hygiene, diarrhea, malaria, immunization). Time constraints in pediatricians and competing priorities could explain this problem. The challenge for healthcare providers to reduce these pathologies is to provide services of sufficient quality and clarity. All medical stakeholders have an important role to play.

[Pregnancy in patients with a history of ischaemic heart disease - Case series and literature review]. / Grossesse chez les patientes ayant un antécédent de cardiopathie ischémique - Série de cas et revue de la littérature.

Heart diseases complicate 1 to 3% of pregnancies and are the leading cause of indirect maternal deaths. Prior ischaemic heart event in pregnant patients is increasing. Most knowledge is based on few reports and there are no French nor international recommendations about the specific management of these patients. The specificity of the management of these patients during pregnancy, delivery and post-partum depends on the severity of the prior cardiac event and its consequences. This will be illustrated by the report of four recent cases managed in our hospital. First patient had myocardial infarction with normal left ventricular ejection fraction (LVEF). Second patient had a Tako-Tsubo syndrome with LVEF 45%. Third patient had ischemic cardiopathy with LVEF 30%. Fourth patient had myocardial infarction with LVEF 20%. A multidisciplinary follow-up should be required, especially in patients with severe ventricular dysfunction. The risk of fetal growth restriction appears to be increased, suggesting that closer ultrasound monitoring is necessary.

[Acute or sub-acute thrombosis of steel stents]. / Thrombose aiguë ou subaiguë des stents en acier. A propos d'une série consécutive de 2 997 patients.

The use of coronary endoprostheses has greatly contributed to the improvement in the results of coronary angioplasty. Nevertheless, the risk of stent thrombosis remains a major preoccupation. We studied a retrospective series of 2997 patients who had undergone coronary angioplasty between 1999 and 2003. 36 patients (1.2%) had an acute or sub-acute stent thrombosis, occurring in two thirds of cases in the first 4 days with particularly serious clinical consequences: 5 deaths (13.8%) and 27 myocardial infarctions (75%). A comparison between the 2 groups of patients with thrombosis (n = 36) and without thrombosis (n = 2961) using multivariate analysis determined predictive factors for thrombosis: systolic LV dysfunction < 40% (p < 0.0001 OR 3.8 [2-7.3]), angioplasty for lesions on the anterior interventricular artery (p < 0.0001 OR 2.7 [1.4-5]), angioplasty performed in the acute phase of MI (p < 0.05 OR 13.9 [6.7-29.2]), B2-type complex lesions (p < 0.01 OR 2.5 [1.3-5]), residual dissection at the dilated site (p < 0.02 OR 5.1 [1.4-18.2]). More than ever, acute thrombosis remains a topical subject. This study emphasises the incidence of steel stent thrombosis; the clinical consequences and the predictive factors for early occlusion.

[Mycoplasma pneumoniae, community-acquired pneumonia and asthma]. / Mycoplasma pneumoniae, pneumonies et asthme.

Mycoplasma pneumoniae is an intracellular pathogen, devoid of cell wall, able to invade airway epithelial cells. Infection may either remain asymptomatic or induce bronchitis and pneumonia. M. pneumoniae is the first-ranking aetiological agent of community-acquired pneumonias in children over five years of age. Clinical features are usually mild, but this should not preclude the initiation of a treatment, in order to avoid serious sequelae such as impairment of pulmonary gas exchange capacity. In children at high-risk of asthma, infection with M. pneumoniae can induce exacerbation. A survey was performed in children admitted to hospital Saint-Vincent-de-Paul (Paris) for an episode of severe asthma exacerbation with persistent hypoxemia. Mycoplasma infection was identified in 26% of children with a history of asthma and 50% of those for whom the exacerbation was the presenting manifestation of the disease. Furthermore, if the Mycoplasma infection was atypical, asthma exacerbation recurred within one month. M. pneumoniae should be considered not only as a preeminent agent of respiratory infection in children, but also as a triggering factor in exacerbation and even inception of asthma. As a consequence, it is mandatory to carefully search for and actively treat Mycoplasma infection in children.