Transient hypertransaminasemia in paediatric patients with Crohn disease undergoing initial treatment with enteral nutrition.

Item does not contain fulltex

B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia.

Contains fulltext : 95667.pdf (publisher's version ) (Open Access

Discontinuation of biologic DMARDs in non-systemic JIA patients: a scoping review of relapse rates and associated factors

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) have changed the treatment of juvenile idiopathic arthritis (JIA) patients notably, as bDMARDs enable substantially more patients to achieve remission. When sustained remission is achieved, tapering or even discontinuation of the bDMARD is advocated, to reduce side effects and costs. However, when and how to discontinue bDMARD therapy and what happens afterwards, is less known. OBJECTIVES: With this scoping review we aim to collect available data in current literature on relapse rate, time to relapse (TTR) and possible flare associated variables (such as time spent in remission and method of discontinuation) after discontinuing bDMARDs in non-systemic JIA patients. METHODS: We performed a literature search until July 2022 using the Pubmed database. All original studies reporting on bDMARD discontinuation in non-systemic JIA patients were eligible. Data on patient- and study characteristics, the applied discontinuation strategy, relapse rates and time to relapse were extracted in a standardized template. RESULTS: Of the 680 records screened, 28 articles were included in this review with 456 non-systemic JIA patients who tapered and/or stopped bDMARD therapy. Relapse rate after discontinuation of bDMARDs, either abruptly or following tapering, were 40-48%, 36.8-45.0% and 60-78% at 6, 8 and 12 months respectively. Total relapse rate ranged from 26.3% to 100%, with mean time to relapse (TTR) of 2 to 8.4 months, median TTR 3 to 10 months. All studies stated a good response after restart of therapy after flare. JIA subtype, type of bDMARD, concomitant methotrexate use, treatment duration, tapering method, age, sex, and time in remission could not conclusively be related to relapse rate or TTR. However, some studies reported a positive correlation between flare and antinuclear antibodies positivity, younger age at disease onset, male sex, disease duration and delayed remission, which were not confirmed in other studies. CONCLUSION: Flares seem to be common after bDMARD discontinuation, but little is known about which factors influence these flares in JIA patients. Follow up after discontinuation with careful registration of patient variables, information about tapering methods and flare rates are required to better guide tapering and/or stopping of bDMARDs in JIA patients in the future

[Borrelial lymphocytoma]

BACKGROUND: Borrelial lymphocytoma is a relatively rare but typical presentation of Lyme disease. Predilection sites are the ears in children and chest/nipples in adults. It is treated like an erythema migrans and has a good prognosis. CASE DESCRIPTION: A 16-year-old boy presented with a swollen, red and painful right nipple since several months. An ultrasound showed normal breast tissue. The patient was referred to the pediatric surgeon who performed an incision biopsy. Histopathological examination revealed follicular hyperplasia without signs of malignancy. An infectious cause, most likely Lyme disease, was suspected. Serological analysis and PCR of the tissue confirmed the diagnosis of a borrelial lymphocytoma, and the patient was treated with doxycycline with good result. CONCLUSION: Early recognition of the characteristic clinical presentation of borrelial lymphocytoma, supported by positive results from serologic testing for Lyme disease, avoids the need for additional and invasive diagnostic tests

Elever tvingas leta efter negativa tankar : Forskare kritiserar program som används i skolan

Hypogammaglobulinaemias are the most common primary immunodeficiency diseases. This group of diseases is very heterogeneous, and little is known about these diseases in children. In the Pediatric Predominantly Antibody Deficiencies (PedPAD) study, we analysed data from the European Society for Immunodeficiencies (ESID) online database to gain more insight into the characteristics of children with hypogammaglobulinaemia; 46 centres in 18 different countries agreed to participate. Data from 2076 of the 3191 children who were registered at the time of data extraction with a diagnosis of hypogammaglobulinaemia (this excludes agammaglobulinaemia and defects in class-switch recombination) were available for analysis. The data set showed several limitations. Because of country-related differences in diagnostic criteria used for the classification of different types of primary hypogammaglobulinaemia, further analysis of the data was performed in the combined data set. The most striking observation is the strong majority of male patients in the group of children with primary hypogammaglobulinaemia (n = 1292, 63%). This male predominance was observed in each of the 18 countries involved. The boys were younger at diagnosis (mean age males 5·3 years; mean age females 5·8 years). Moreover, one or more complications were more frequently reported in boys (12%) compared to girls (5%). The male predominance suggests that patients with an undetected or unknown X-linked genetic cause are included in this group of children registered as primary hypogammaglobulinaemia

Gene signature fingerprints stratify SLE patients in groups with similar biological disease profiles: a multicentre longitudinal study

OBJECTIVES: Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. METHODS: Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n = 101 and n = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. RESULTS: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. CONCLUSIONS: The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices

Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: A retrospective cohort study

Contains fulltext : 285281.pdf (Publisher’s version ) (Open Access

Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: A retrospective cohort study

Background: De novo variants (DNVs) are currently not routinely evaluated as part of diagnostic whole exome sequencing (WES) analysis in patients with suspected inborn errors of immunity (IEI). Methods: This study explored the potential added value of systematic assessment of DNVs in a retrospective cohort of 123 patients with a suspected sporadic IEI that underwent patient-parent trio-based WES. Results: A (likely) molecular diagnosis for (part) of the immunological phenotype was achieved in 12 patients with the diagnostic in silico IEI WES gene panel. Systematic evaluation of rare, non-synonymous DNVs in coding or splice site regions led to the identification of 14 candidate DNVs in genes with an annotated immune function. DNVs were found in IEI genes (NLRP3 and RELA) and in potentially novel candidate genes, including PSMB10, DDX1, KMT2C, and FBXW11. The FBXW11 canonical splice site DNV was shown to lead to defective RNA splicing, increased NF-kappa B p65 signalling, and elevated IL-1 beta production in primary immune cells extracted from the patient with autoinflammatory disease. Conclusions: Our findings in this retrospective cohort study advocate the implementation of trio-based sequencing in routine diagnostics of patients with sporadic IEI. Furthermore, we provide functional evidence supporting a causal role for FBXW11 loss-of-function mutations in autoinflammatory disease.Genetics of disease, diagnosis and treatmen