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Autoimmune lymphoproliferative syndrome (ALPS) is a primary disorder of lymphocyte homeostasis, leading to chronic lymphoproliferation, autoimmune cytopenia, and increased risk of lymphoma. The genetic landscape of ALPS includes mutations in FAS, FASLG, and FADD, all associated with apoptosis deficiency, while the role of CASP10 defect in the disease remains debated. In this study, we aimed to assess the impact of CASP10 variants on ALPS pathogenesis. We benefit from thousands of genetic analysis datasets performed in our Institute's genetic platform to identify individuals carrying CASP10 variants previously suspected to be involved in ALPS outcome: p.C401LfsX15, p.V410I and p.Y446C, both at heterozygous and homozygous state. Clinical and laboratory features of the six included subjects were variable but not consistent with ALPS. Two individuals were healthy. Comprehensive analyses of CASP10 protein expression and FAS-mediated apoptosis were conducted and compared to healthy controls and ALPS patients with FAS mutations. Missense CASP10 variants (p.V410I and p.Y446C), which are common in the general population, did not disrupt CASP10 expression, nor FAS-mediated apoptosis. In contrast, homozygous p.C401LfsX15 CASP10 variant lead to a complete abolished CASP10 expression but had no impact on FAS-mediated apoptosis function. At heterozygous state, this p.C401LfsX15 variant lead to a reduced CASP10 protein levels but remained associated with a normal FAS-mediated apoptosis function. These findings demonstrate that CASPASE 10 is dispensable for FAS-mediated apoptosis. In consequences, CASP10 defect unlikely contribute to ALPS pathogenesis, since they did not result in an impairment of FAS-mediated apoptosis nor in clinical features of ALPS in human. Moreover, the absence of FAS expression up-regulation in subjects with CASP10 variants rule out any compensatory mechanisms possibly involved in the normal apoptosis function observed. In conclusion, this study challenges the notion that CASP10 variants contribute to the development of ALPS., (© 2024. The Author(s).)

Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease's natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37·4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (<200/mm 3 ), high lymphocyte count (>3000/mm 3 ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Acute haematogenous bone and joint infections (AHBJI) represent a diagnostic and therapeutic emergency in children, with significant potential sequelae in the case of delayed treatment. Although historically the recommendations for treatment have been based on surgery and prolonged antibiotic therapy, recent studies have demonstrated that short-course antibiotic therapy is also effective., Objectives: We evaluated a short-term antibiotic protocol for both osteomyelitis and septic arthritis in a 6 year retrospective study at the University Hospital of Montpellier., Methods: This protocol was based on an initial intravenous treatment with a re-evaluation after 48 h and an early switch to oral therapy in the case of a favourable clinical course for a minimum total duration of 15 days. Antibiotics were selected based on local microbiological epidemiology and systematically adapted to bacteriological results., Results: One hundred and seventy-six cases of AHBJI were included, comprising 56 patients with osteomyelitis, 95 with septic arthritis and 25 who had both of these. The aetiological agent was identified in 42% of the cases, with the main pathogens being Staphylococcus aureus (39%) and Kingella kingae (27%). The mean intravenous treatment duration was 4 days, while the total treatment duration was 15 days. There were no treatment failures, mild sequelae occurred in 1% of the cases and the secondary surgical revision rate was 7%., Conclusions: The results of this study are comparable to those reported for evaluations of prolonged antibiotic therapy protocols, thus indicating that a common short-term antimicrobial therapy for the management of both osteomyelitis and septic arthritis (minimum of 15 days) is a viable option for treating AHBJI in children. Further prospective studies to confirm these findings are hence warranted., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

DRESS syndrome (drug reaction eosinophilia and systemic symptoms) is a rare and serious drug toxidermia with potentially multiple organ dysfunctions. This report relates the case of a 9-year-old girl who presented a right cervical and mediastinal adenopathy with a mediastinal lump, fever, and deterioration of the general condition. The hospital assessment concluded in an abscess due to Staphylococcus aureus secreting a Panton-Valentine toxin with nonsevere pleuritis and pericarditis. The outcome was favorable with antibiotic treatment consisting of amoxicillin-acid clavulanic, amikacin, and clindamycin followed by oxacillin, rifampicin, and colchicine. On the 25th day of treatment, she presented recurrence of fever with a generalized rash, moderate hepatic cytolysis, hypereosinophilia, with the presence of activated lymphocytes that were further suggestive of visceral DRESS syndrome. A skin biopsy was performed that confirmed the diagnosis. The outcome was favorable after stopping all ongoing treatments even though none of the administered treatments were classically responsible for the syndrome. Symptomatic treatments (antihistaminic and topical steroids) were also administered. Patch tests, performed secondarily, were positive to penicillins; amoxicillin-clavulanic acid or oxacillin were then suspected of being responsible for the DRESS syndrome. Potentially serious, the DRESS syndrome should be considered together with atoxic epidermal necrolysis or Stevens-Johnson syndromes in the case of any rash appearing after drug administration, especially in the presence of face and eyelid edema., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Mycoplasma pneumoniae-associated nephritis has been reported in children with various pathological findings. It nevertheless remains an uncommon disease and, within this clinical context, endo-and extracapillary glomerulonephritis in a child has never been described. We report here a case of a 3-year-old girl diagnosed with severe crescentic glomerulonephritis associated with M. pneumoniae infection who presented with nephrotic syndrome and impaired renal function. The serum C3 complement level was initially low but returned to normal after 1 month. Two courses of three methylprednisolone pulses were administered in association with plasmapheresis and, secondarily, mycophenolate mophetil. This treatment regimen led to disease remission and a favorable renal outcome at the 6-month follow-up. However, the treatment guidelines in this situation remain debatable.