[From pediatric care to adult medicine: Transition of sickle cell patients, a French monocentric study]. / De la pédiatrie à la médecine adulte : transition des patients drépanocytaires, une étude monocentrique française.

Sickle cell disease, a hemoglobin disorder with autosomal recessive transmission, is one of the most common genetic diseases screened in France. Thanks to early management, 95% of sickle cell patients reach adulthood and require transition from pediatric care to adult care. Through a retrospective study of records from serious sickle cell patients over 17 years old, followed in the hematology-oncology pediatric unit of Reims University Hospital Center in France, we analyzed transition conditions, compared pediatric and adult management, and proposed a plan for transition care. As of 1 January 2016, out of 19 sickle cell patients meeting the inclusion criteria, 12 had made the transition from pediatric care to adult medicine. Among the transition group, the transition was proposed by the pediatrician in 92% of cases. The average age of transition was 19.4 years. The time between receiving the information and the last pediatric visit was 2.4 months. Seven out of the 12 patients were informed of their transition during the last pediatric visit. The age of the first adult visit was 20.3 years. There was no alternate or joint consultation. The treatments prescribed during the last pediatric visit were not modified during the first adult visit. The average number of hospitalizations per patient was 2.7 in pediatric care and 3.4 in adult care with a median value of 2 in both groups. Three out of 12 patients died, the average age of death being 26.7 years. Transition is an important milestone in chronic disease patients. More than age, the maturity of the patient must be taken into account. The transition to the adult structure requires early preparation in the teenage years and investment of the adolescent and his family as well as investment of pediatric and adult caregivers. This study points out the need to establish a transition plan within our hospital in collaboration with adult physicians. Continuity of care is necessary to increase the quality of managing patients and cannot be done without a close relationship between pediatric specialists and adult physicians.

[An indolent and fluctuating subcutaneous mass of the skull in a 5-year-old patient: Diagnostic approach and difficulties]. / Une masse indolente et fluctuante sous-cutanée du crâne chez une patiente de 5 ans : démarche et difficultés diagnostiques.

A subcutaneous mass of the skull in children can have many different causes (infectious, tumoral, and inflammatory). We report on the case of a 5-year-old patient with a subcutaneous mass of the skull evolving over several months. The first pathological analysis concluded in Kimura disease. The progression and scarcity of this entity in children led to a second pathological analysis that showed lymphoblastic lymphoma B (LLB). This case reminds us that when there are discrepancies between pathological conclusions and clinical progression of a tumoral process, repeated analysis and immunochemistry are necessary.

[Pancreatic infringement exocrine and endocrine in cystic fibrosis]. / Atteinte pancréatique exocrine et endocrine dans la mucoviscidose.

The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent phase of diabetes, screening it is recommended by the realization of an annual OGTT from 10 years of age, or before in severe forms of CF. New treatments of CF able to target CFTR showed their efficacy in slowing the decline of lung function, and could also contribute to slow or prevent the onset of diabetes.

[National consensus regarding azithromycin use in cystic fibrosis]. / Consensus national sur la prescription de l'azithromycine dans la mucoviscidose.

AIM: To propose a formalized consensus agreement regarding the prescription of azithromycin in cystic fibrosis (CF). MATERIAL AND METHODS: Application of the Delphi method in 5 thematic fields: indications, contra-indications, dosage, precautions for use and treatment follow-up. RESULTS: Thirty identified French CF centers participated in the process on 49 (61%), which comprised 3 rounds. Experts validated azithromycin as a long-term anti-inflammatory agent in children aged over 6 years, presenting with the classical form of CF, irrespective of the bacteriological status of the patient (except for non-tuberculous mycobacteria). Azithromycin administration should not be routine in the milder forms of the disease, and avoided in the presence of severe hepatic or renal involvement. In children whose weight is below 40 kg, a strong consensus recommended a single daily oral dose, administered three times weekly. However, in adults, the level of agreement was weaker. Minimal duration of treatment is 6 months, after which the drug should be discontinued if no observable effect is noted on clinical parameters, exacerbation rate and/or FEV1. Clinical monitoring of treatment tolerance is recommended (nausea, diarrhea, skin rash, tinnitus, deafness, arthropathy), without increasing the frequency of surveillance of sputum bacteria. However, it is essential to monitor sputum for fungi (expectoration, Aspergillus, broncho-pulmonary allergic aspergillosis). CONCLUSION: This consensus statement defines an area for the prescription of azithromycin in CF, with the aim of better harmonization of its use.

Management of pancreatic, gastrointestinal and liver complications in adult cystic fibrosis.

INTRODUCTION: The gastrointestinal tract is a major source of morbidity in adults with cystic fibrosis (CF), with a wide range of complications, some of them being specific to the underlying disease. STATE OF KNOWLEDGE: Abnormal CFTR function, with reduced bicarbonate and other ion transport levels through the apical surface of epithelial cells, affects the intestinal tract including the pancreas and the liver. Similarly to what is observed in the respiratory tract, gastrointestinal CFTR dysfunction leads to mucus accumulation, dysmotility, small bowel bacterial overgrowth and inflammation with alteration of innate immune responses, all of which being likely to be interrelated. In developed countries, almost half of patients with CF are adults followed in multidisciplinary CF care centres by pneumologists who often have to manage gastrointestinal complications. CONCLUSION: It therefore appears essential that adult gastroenterologists develop the expertise needed for managing CF gastrointestinal complications in close collaboration with multidisciplinary CF care centre teams to improve the quality of life of adults with CF.

How to minimize toxic exposure to pyridine during continuous infusion of ceftazidime in patients with cystic fibrosis?

Ceftazidime is particularly efficient against Pseudomonas aeruginosa in cystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises some concern. Our aim was to examine the kinetics of degradation of ceftazidime in portable infusion pumps either at 4°C, 22°C, or 33°C and to propose some recommendations in order to reduce the pyridine exposure. Two administration models were studied in vitro. In model 1, we administered 12 g of ceftazidime infused over 23 h (once-daily infusion) compared to 6 g infused over 11.5 h in model 2 (twice-daily regimen). Samples were collected at 0 h and then every 4 and 2 h after the shaping of portable infusion pumps in models 1 and 2, respectively. Both ceftazidime and pyridine were analyzed using an ultraviolet high-performance liquid chromatograph. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment decreases at a ratio close to 1/6 and 1/3 between 33°C and 4°C in models 1 and 2, respectively. Regardless of the conditions, the production of pyridine is significantly lower in model 2, whereas the total delivery amount of ceftazidime is significantly higher at 4°C and 33°C compared to that in model 1. According to a the precautionary principle, these findings lead to three major recommendations: (i) exposing a solution of ceftazidime to over 22°C should be strictly avoided, (ii) a divided dose of 6 g over 11.5 h instead of a once-daily administration is preferred, and (iii) infusion should be administered immediately after reconstitution.

[A retrospective study to evaluate a protocol aimed at reducing the number of unnecessary voiding cystourethrographies performed after a first episode of febrile urinary tract infection]. / Évaluation d'un protocole de limitation des indications de cystographie dans les infections urinaires fébriles.

AIM: Whether or not voiding cystourethrography (VCUG) should be performed after a first episode of urinary tract infection (UTI) remains a matter of debate. The role of VCUG is primarily to diagnose high-grade vesicoureteral reflux (≥grade III) (VUR) and hence prevent the development of renal scars and poor long-term outcome. We designed a protocol designed to reduce the indications for performing unnecessary VCUGs after a first episode of febrile UTI. In order to evaluate the efficacy of our protocol, we designed a retrospective study to verify whether high-grade VUR was subsequently being underdiagnosed. METHODS: This study compared the number of cases of VUR diagnosed over 2 1-year periods in children aged 1 month to 18 years. Data were collected from records held in the pediatric emergency department of the University Hospital of Reims. All cases included had presented to the department with a first episode of febrile UTI. During the first 1-year collection period, all patients underwent a VCUG. During the second collection period, the protocol was in place and VCUG was only performed in children with a serum procalcitonin level greater than 1 ng/L and/or an abnormal renal ultrasound scan. RESULTS: During the first year, 100 patients underwent routine VCUG and 7 cases of high-grade VUR were diagnosed. During the following year, VCUG was limited according to the new protocol: 102 patients were enrolled, 52 VCUGs were performed and 8 cases of high-grade VUR were diagnosed. Cases of low-grade VUR (I and II) were less frequently detected, without significant consequences for the patients. CONCLUSION: The protocol led to a 40% decrease in the number of VCUGs performed. No cases of high-grade VUR were missed; however, the number of VCUGs performed with a normal outcome remained significant.

[Acute idiopathic scrotal oedema in young boys: A report of ten cases and a review of the literature]. / Œdème aigu scrotal idiopathique de l'enfant : présentation d'une série de dix cas et revue de la littérature.

BACKGROUND: acute idiopathic scrotal oedema (AISO) is most commonly seen in boys aged between 5 and 10 years. It comprises a benign dermatosis of spontaneously favourable outcome but requiring surgical exploration in some cases in order to rule out testicular torsion. Our retrospective study of a series of 10 children presenting AISO allowed us to set out the specific features of this dermatological disorder well-known to paediatric surgeons, but concerning which only one publication exists in the dermatology literature. PATIENTS AND METHODS: this was a retrospective study of the files of all children seen in the paediatric surgery department of Reims University Hospital between 1996 and 2008 for acute scrotal oedema. Diagnosis of AISO was made on the basis of clinical criteria after ruling out potential differential diagnosis. The demographic, clinical and laboratory data were collated from patient files. Long-term outcome was determined by means of telephone calls. RESULTS: among 185 cases of acute scrotal disease, 10 cases of AISO (5.4%) were identified. The mean age at onset of the initial episode was 6 years (range: 3 to 12 years). Oedema was unilateral in eight cases and bilateral in two cases; there was involvement of the inguinal folds, the perineum and the homolateral buttock in three cases, and of the penis in one case. The skin was erythematous and relatively non-inflamed in all but one case. Non-focal scrotal pain was present on palpation in nine cases. General health status was unimpaired and none of the children presented any associated signs. White cell count was between 7000 and 12000 per millimeter cube, with no neutrophil polynucleosis or inflammatory syndrome; in three cases, hypereosinophilia was between 700 and 2300 per millimeter cube. Two patients underwent surgical exploration to rule out testicular torsion; Doppler ultrasound was performed in the remaining eight cases and no surgery was required in six cases. In all cases, a favourable outcome was attained within 2 to 3 days and there were no sequelae. Five children presented a total of 21 recurrences (between three and eight per child) over a maximum period of 12 years. DISCUSSION: the clinical characteristics of our patients are entirely consistent with the descriptions given in the literature. The chief problem with AISO is differential diagnosis; in this respect, Doppler ultrasound may be useful in obviating surgical investigation for testicular torsion. Treatment involves bed rest and analgesics where necessary; a rapidly favourable outcome is achieved within 2 to 3 days, but relapse occurs in at least 20% of cases, although these were more frequent and more numerous in our series. The aetiopathogenesis has not yet been fully elucidated. CONCLUSION: Identification of AISO, a fairly stereotypical though misunderstood diagnostic entity, is useful in order to avoid unwarranted medical treatment and, above all, unnecessary surgical exploration.

[Mild cystic fibrosis: genetics - extending follow-up is necessary]. / Les formes atténuées de la mucoviscidose : génétique - suivi prolongé nécessaire.

The diagnosis of mild cystic fibrosis is first suspected on mild lung disease or absence of pancreatic insufficiency and is assessed by biological analysis. The sweat test is not always conclusive. The nasal potential difference and molecular analysis of CFTR gene allow confirming diagnosis. A regular follow-up in cystic fibrosis clinical centre is essential all life long. The genotype, especially during neonatal period, cannot be used to predict individually the course of the disease. Genetic counselling must be recommended to the parents in order to propose an analysis of CFTR gene to give the appropriate genetic counselling and to consider with them which family members could be concerned, especially in the event of parental project. The research of heterozygote status in related for prenatal diagnosis is not recommended for all mutations.

[Measurement of pulmonary inflammation in cystic fibrosis]. / Mesure de l'inflammation pulmonaire dans la mucoviscidose.

Lung inflammation is a pivotal phenomenon in the pathogenesis of cystic fibrosis. Inflammation can be measured and quantified within a research perspective, as well as in daily clinical practice. In this review paper, the "Inflammation Task Force" of the "Société Française de Mucoviscidose" has reviewed the literature regarding the various techniques currently available (bronchoalveolar lavage, sputum analysis, nasal wash and brushing, exhaled breath condensates, carbon monoxide and nitric oxide, and systemic measurements (plasma and urine)). The interpretation of all these determinations in children and adults is also discussed.

[Treatment of airway inflammation in cystic fibrosis]. / Traitement de l'inflammation bronchique dans la mucoviscidose.

Cystic fibrosis airway inflammation is characterized by neutrophilic efflux and high levels of proinflammatory cytokines such as IL-8 and IL-6. Inhaled corticosteroids are widely used despite lack of evidence of efficacity. Despite evidence of efficacity of ibuprofen, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects. Azithromycin has antiinflammatory properties and is effective in cystic fibrosis (CF) patients. Deoxyribonuclease (rhDNase) has been shown to improve lung function in patients with cystic fibrosis and may also have a positive effect on inflammation. Other antiinflammatory drugs are in the process of validation.

Dysregulation of IL-2 and IL-8 production in circulating T lymphocytes from young cystic fibrosis patients.

It is well documented that patients with cystic fibrosis (CF) are unable to clear persistent airway infections in spite of strong local inflammation, suggesting a dysregulation of immunity in CF. We and others have reported previously that T lymphocytes may play a prominent role in this immune imbalance. In the present work, we compared the reactivity of CD3+ T cells obtained from young CF patients in stable clinical conditions (n = 10, aged 9-16.5 years) to age-matched healthy subjects (n = 6, aged 9-13.5 years). Intracellular levels of interferon (IFN)-gamma, interleukin (IL)-2, IL-8 and IL-10 were determined by flow cytometry after whole blood culture. The data identified T lymphocyte subsets producing either low levels (M1) or high levels (M2) of cytokine under steady-state conditions. We found that the production of IFN-gamma and IL-10 by T lymphocytes was similar between young CF patients and healthy subjects. In contrast, after 4 h of activation with PMA and ionomycin, the percentage of T cells producing high levels of IL-2 (M2) was greater in CF patients (P = 0.02). Moreover, T cells from CF patients produced lower levels of IL-8, before and after activation (P = 0.007). We conclude that a systemic immune imbalance is present in young CF patients, even when clinically stable. This disorder is characterized by the capability of circulating T lymphocytes to produce low levels of IL-8 and by the emergence of more numerous T cells producing high levels of IL-2. This imbalance may contribute to immune dysregulation in CF.