BACKGROUND: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. OBJECTIVES: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. METHODS: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. RESULTS: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. CONCLUSIONS: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
- MeSH
- 1-fosfatidylinositol-3-kinasa * genetika MeSH
- antigen CTLA-4 genetika MeSH
- fosfatidylinositol-3-kinasy třídy I MeSH
- fosfatidylinositol-3-kinasy genetika MeSH
- lidé MeSH
- mutace MeSH
- primární imunodeficience * genetika MeSH
- registrace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.
- MeSH
- COVID-19 * etiologie MeSH
- dítě MeSH
- homologní transplantace MeSH
- infekční nemoci * etiologie MeSH
- kašel etiologie MeSH
- kostní dřeň MeSH
- lidé MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- SARS-CoV-2 MeSH
- testování na COVID-19 MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Emerging invasive fungal infections (IFI) have become a notable challenge. Apart from the more frequently described fusariosis, lomentosporiosis, mucormycosis, scedosporiosis, and certain dematiaceae or yeasts, little is known about extremely rare IFI. METHODS: Extremely rare IFI collected in the FungiScopeⓇ registry were grouped as Dematiaceae, Hypocreales, Saccharomycetales, Eurotiales, Dermatomycetes, Agaricales, and Mucorales. RESULTS: Between 2003 and June 2019, 186 extremely rare IFI were documented in FungiScopeⓇ. Dematiaceae (35.5%), Hypocreales (23.1%), Mucorales (11.8%), and Saccharomycetales (11.3%) caused most IFI. Most patients had an underlying malignancy (38.7%) with acute leukemia accounting for 50% of cancers. Dissemination was observed in 26.9% of the patients. Complete or partial clinical response rate was 68.3%, being highest in Eurotiales (82.4%) and in Agaricales (80.0%). Overall mortality rate was 29.3%, ranging from 11.8% in Eurotiales to 50.0% in Mucorales. CONCLUSIONS: Physicians are confronted with a complex variety of fungal pathogens, for which treatment recommendations are lacking and successful outcome might be incidental. Through an international consortium of physicians and scientists, these cases of extremely rare IFI can be collected to further investigate their epidemiology and eventually identify effective treatment regimens.
Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.
- MeSH
- dítě MeSH
- infekční nemoci * MeSH
- kostní dřeň MeSH
- lidé MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výzkum MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
