Dramatic improvement of severe cryptococcosis-induced immune reconstitution syndrome with adalimumab in a renal transplant recipient.

In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.

Uveitis in children: Epidemiological, clinical and prognostic characteristics.

PURPOSE: The purpose of this study is to describe the characteristics and prognostic factors of pediatric uveitis in a French university referral hospital. METHODS: We performed a retrospective study of all cases of all pediatric uveitis seen at our institution over a 7-year period. RESULTS: A total of 141 eyes of 86 children were included. The mean age was 10.7 years, and 61.6% were girls. The uveitis was bilateral in 64.0% of cases. Anterior uveitis (41.0%) and intermediate uveitis (32.0%) were the most frequent forms. The most frequent etiologies were idiopathic (27.9%), juvenile idiopathic arthritis (25.6%) and pars planitis (18.6%). During the follow-up period, systemic corticosteroids were received by 43.0% of children, immunosuppressive drugs by 31.4% and biological agents by 18.6%. At the final examination, complications were present in 67.0% of patients: 18.0% had cataracts, and 11.3% had intraocular hypertension. Posterior synechiae were present in 27.6% of eyes, optic disc edema in 10.5% and macular edema in 16.2%. At the last visit, visual acuity was better than 20/200 in 97.0% of cases. The presence of band keratopathy, cataract or glaucoma was an independent predictor of impaired visual outcomes at follow-up. CONCLUSION: Juvenile idiopathic arthritis is one of the most frequent and severe pediatric uveitides. Close monitoring and early treatment could prevent complications.

[Transition from pediatric to adult care: Recommendations of the French network for autoimmune and autoinflammatory diseases (FAI2R)]. / La transition de la pédiatrie à l'âge adulte : recommandations de prise en charge de la filière des maladies auto-immunes et auto-inflammatoires rares FAI2R.

Autoimmune and autoinflammatory diseases (AIDs) are a heterogeneous group of diseases. They can occur in childhood and account for significant morbidity and mortality. Transitioning from pediatric to adult healthcare can be difficult for patients and their families. It can interfere with patient follow-up and management, and eventually lead to complications. Although recommendations exist for the successful transition of patients with chronic diseases, few are specifically adapted to children and adults with AIDs (Suris et al., 2015-Solau-Gervais, 2012). The French working group on transition of the rare autoimmune and autoinflammatory diseases presents its reflections and recommendations for a successful transition. Preparation for transition should start early. Its goals are to empower adolescents by providing them with the knowledge to manage their own care, respond appropriately to changes in their condition, and evolve within the adult healthcare system. This requires the active participation of the patient, his or her family, as well as the pediatric and adult medical teams. The transition process involves multidisciplinary care and dedicated therapeutic education programs. Finally, the identification of medical specialists by region, trained in rare AIDs and accompanied by expert patients, may improve the management of patients with rare AIDs from adolescence to adulthood.

Clinical outcome in children with chronic recurrent multifocal osteomyelitis.

OBJECTIVE: To determine the clinical outcome of children with chronic recurrent multifocal osteomyelitis (CRMO). METHODS: We retrospectively reviewed clinical, biological and radiological data of children with CRMO at five French paediatric centres. Outcome data were obtained through review of hospital charts and questionnaires sent to all patients to assess disease activity and educational and vocational achievement. RESULTS: Forty patients were assessed (34 females and 6 males) with a median age at diagnosis of 11.5 yrs (range 2-17). Median number of initial bony lesions was 2 at onset, and 3.5 over disease course. Median time since diagnosis was 3.5 yrs (range 0.5-15) and median duration of active disease 2.7 yrs (range 0.5-13.5). Nine (22.5%) patients had psychological or physical sequelae. Twenty-nine children (72.5%) responded to the questionnaire. Twenty-six had no physical disability as judged by the HAQ 0-1, two had moderate disability (HAQ: 1-2) and one had severe disability (HAQ: 2-3). Seventeen patients (58.6%) had active disease at follow-up (after 6 months to 15 yrs since diagnosis) and continued to have pain (median value of visual analogue scale: 10/100). CRMO had interfered with patient's education in two cases. CONCLUSIONS: Clinical outcome of children with CRMO is generally good, but a sizeable proportion of patients have active disease at follow-up, and a minority of patients can have a severe and prolonged disease course despite intensive treatments. Further studies are required to determine predictive factors for severe disease.

Lymphocyte expansion after unrelated cord blood allogeneic stem cell transplantation in adults.

Limited information is available regarding the incidence and features of lymphocyte expansions after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Large granular lymphocytes (LGL) expansions have been reported after bone marrow or peripheral blood, but not after unrelated cord blood (UCB) allo-HSCT, associated with indolent clinical courses and favorable outcomes. Here, we considered 85 recipients of UCB allo-HSCT to more broadly define the impact of lymphocytosis, not limited to LGL. Sustained lymphocytosis was observed in 21 (25%) patients at a median onset of 12.6 months and with a median duration of 12 months. Immunophenotypic analysis showed predominantly CD8+ T and/or polyclonal B-cell expansions. Three patients only had monoclonal T-cell expansion. CMV reactivation was significantly more frequent in the group of patients with lymphocytosis (76% vs 28%, P=0.0001), but was not associated with survival. Conversely, 2-year disease-free survival and overall survival were significantly higher for lymphocytosis patients (85% vs 55%, P=0.01 and 85% vs 63%, P=0.03, respectively). In conclusion, expansion of T or B lymphocytes after UCB allo-HSCT in adults is not a rare event. Although occurring relatively late after transplant, this feature is predictive of a better outcome for the patients.

[Neonatal lupus syndromes]. / Le lupus néonatal.

Children born from mothers positive for autoantibodies against SSA/Ro and/or anti-SSB/La ribonucleoproteins may develop heart conduction tissue damage resulting in atrioventricular block and/or transient skin rash, liver enzyme abnormalities and anaemia/thrombocytopenia. Additional transient electrocardiographic abnormalities (sinus bradycardia, QT interval prolongation) have been reported. Such clinical and laboratory manifestations are included in the so-called neonatal lupus syndromes, independently whether the mother is suffering from a systemic autoimmune disease or is totally asymptomatic. The prevalence of the congenital heart block is around 2%, of neonatal rash around 20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 40% of cases. The risk of recurrence of complete heart block is almost 10 times higher in the following pregnancies. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Their long-term outcome is generally more reassuring than previously assumed. Serial echocardiograms and obstetric sonograms, performed at least every 2 weeks, starting from 16 weeks gestation, are recommended in anti-Ro/SSA positive pregnant women: the goal is to detect early fetal abnormalities, that might precede complete atrioventricular block and that might be a target for preventive therapy. Transplacental passage of maternal anti-SSA/Ro -SSB/La IgG is thought to be pivotal in inducing tissue damage. However, the discordant appearance of the syndrome in twins does suggest a role also for fetal or environmental factors.

[Parents' attitudes towards childhood fever. A cross-sectional survey in the Lyon metropolitan area (202 cases)]. / L'attitude des parents face à la fièvre de leurs enfants. Une enquête transversale des résidents de l'agglomération lyonnaise (202 cas).

INTRODUCTION: The patient overload in pediatric healthcare facilities is caused in part by parents bringing their children in for consultations for fever. We conducted a survey in the Lyon metropolitan area to improve our understanding of parents' attitudes towards their children's fever. OBJECTIVE: To assess the frequency and characteristics of healthcare utilization and evaluate parents' knowledge and attitudes before consulting. METHODS: A random sample of families with at least one child under 6 years of age and living in the Lyon metropolitan area was surveyed by telephone, according to a closed questionnaire that was answered by the person usually responsible for the child's health. RESULTS: 202 families were questioned: 58.9% defined fever as a temperature over 38 degrees C, and 82% used rectal thermometers to measure temperature. Among 144 parents of children with an episode of fever within the previous 12 months, 73% called a physician during the episode, 44% of them immediately. Working-class parents called more frequently (90%) than parents who were professionals or managers (74%). Most parents (94%) administered medication to the child several times before calling the physician. Paracetamol and ibuprofen were mentioned most often. 93% of fever episodes led to consultations. DISCUSSION: Our results show that 59% of the sample defined fever as a temperature equal to 38 degrees C and that fever episodes lead commonly and quickly to physician visits, but that parents do use physical methods and drugs to reduce fever before calling a physician.

A large national cohort of French patients with chronic recurrent multifocal osteitis.

OBJECTIVE: To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors. METHODS: One hundred seventy-eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years. RESULTS: Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome. CONCLUSION: This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

[Acute paediatric care and unplanned consultations - a survey in health care facilities in the "Grand Lyon" area]. / Urgences pédiatriques et consultations non programmées - enquête auprès de l'ensemble du système de soins de l'agglomération lyonnaise.

UNLABELLED: With the increasing number of emergency paediatric consultations, two surveys "on a given day" were performed in the "Communauté Urbaine de Lyon", with the aim of analyzing the causes, circumstances, and relevance of these unplanned consultations, as well as a better understanding of the itinerary of these patients. METHODS: Unplanned consultations concerned children less than 18 years old seen in consultation on Saturday April 21, and Thursday December 13, 2001, in all medical facilities capable of delivering emergency paediatric care. Data collection was performed by filling out a questionnaire given to the family and the physicians (general practitioner who were chosen randomly, or paediatricians volunteering for the study), working in general medicine sectors, at the outpatient emergency consultation of the "Groupement des Pédiatres du Lyonnais", and in all the emergency departments to which children could be addressed (public hospitals and private clinics). "SOS Médecins" did not participate in this study but communicated its activity a posteriori. Six hundred and eighty three consultations on the Saturday and 1183 on the Thursday were analyzed. RESULTS: An estimation of the total number of consultations was performed taking into account the proportion of practitioners participating in the survey, with a total number of 1813 consultations on the Saturday and 4576 on the Thursday. Consultations in the private setting (by practitioners or organized emergency centers) accounted for 82% on the Saturday (general practitioners 70%, paediatricians 12%) and 93% on the Thursday (general practitioners 75%, paediatricians 18%), public hospitals 13% and 4% and private clinics 5% and 2%, respectively. Parents considered the problem to be serious in 10-40% of the cases, depending on the setting. The reason justifying consultation was generally medical (pain or discomfort, fear of complication, less frequently feeling of imminent danger). Non-medical reasons (proximity of the week-end, personal reasons, absence or unavailability of usual practitioner) concerned a fourth of the Thursday consultations and up to half of the Saturday consultations. An urgent consultation was estimated not be justified in 13% of the cases according to the physicians. The main reason for going to a hospital was that "everything would be available on site". On Saturday the absence of the usual practitioner was the most cited reason. The global itinerary was deemed satisfactory by the physicians in 82% of the cases. CONCLUSION: Unplanned consultations are found in three situations: routine and accepted activity of medical office (consultation without an appointment), urgent medical problem (or estimated to be urgent), and the result of a dysfunction between the medical possibilities of the health care system and its use by the parents. This last point opens two possibilities of action which are the information and education of families and the networking of physicians involved in emergency consultations with the aim of reducing hospital consultations by 15-20%.

[A new case of glucose-galactose malabsorption]. / Un nouveau cas de malabsorption du glucose et du galactose.

The authors report a new case of glucose-galactose malabsorption. The particular features of this neonatal life-threatening refractory diarrhea are recalled. The dietetic management which permits a normal growth and psycho-intellectual development is described. The pathophysiological mechanisms of this malabsorption is elucidated from a review of the literature which specifies the autosomal, recessive mode of inheritance.

[Nephrotic syndrome, pancreatitis, hepatitis B. Report of a case]. / Syndrome néphrotique, pancréatite, virus de l'hépatite B. Une observation.

We report on a case of acute pancreatitis in a 9 year-old girl suffering from steroid resistant nephrotic syndrome. Acute abdominal pains revealed pancreatitis whose outcome was favorable after 5 days of total parenteral nutrition. None of the usual causes of pancreatitis was recognized. A serologic profile of hepatitis B, compatible with a chronic carriage of the virus B was found. The possible relationships between pancreatitis, viral hepatitis and the nephrotic syndrome are discussed.