No abstract

T-LGL leukemia has been rarely reported in children. We report a child with T-LGL leukemia who presented with anemia and went on to develop Crohn's disease. Although prednisolone treatment proved effective in the treatment of anemia, large granular lymphocyte counts increased as the doses were tapered. T-cell rearrangement studies revealed a clonal rearrangement of the TCR Vβ/jβ2 gene. Concurrently, the patient developed severe diarrhea. Inflammatory changes across the upper and lower intestines led to the diagnosis of Crohn's disease. This case highlights that T-LGL leukemia could be occurred in children. Flow cytometry and/or T-cell gene rearrangement studies are recommend in patients of anemia and various kind of autoimmune diseases including Crohn's disease, even in children.

Primary prophylaxis is a method of haemostatic management to prevent bleeding and arthropathy in patients with severe haemophilia. The aim of this study was to evaluate the usefulness of primary prophylaxis in patients with severe haemophilia A. This study included 15 patients with haemophilia A who received primary prophylaxis at our institution for a minimum of 5 years. We evaluated the annualized bleeding ratio of joints or other sites, current joint function, and X-ray images and MRI scans taken when patients were 6 years old. The range of patients' ages at the end of the study was 6.2-16.8 years, and at the start of primary prophylaxis it was 0.8-2.4 years. Factor VIII concentrates (25-40 units kg(-1) dose(-1)) were administered 3 times/week or every other day, according to the Swedish protocol. Mean joint and non-joint annualized bleeding ratios were 0.49 ± 0.5 and 1.54 ± 1.69, respectively. At the final evaluation, all patients displayed a normal range of motion for both elbows, knees, and ankles. The radiography and MRI findings at the age of 6 were unremarkable in all patients. Overall, primary prophylaxis for patients with severe haemophilia A was performed safely, reduced the number of bleeding events, and prevented progression to arthropathy.

Background: Increased coagulation factor VIII (FVIII:C) activity is potentially associated with the pathogenesis of glucocorticoid (GC)-induced coagulopathy. However, the mechanism underlying the increase in FVIII:C activity remains unclear. Objectives: We analyzed the changes in coagulation parameters, including FVIII and von Willebrand factor (VWF), in pediatric patients with immune thrombocytopenic purpura (ITP) treated with GC. The influence of GC treatment on mRNA expression of the FVIII (F8) and VWF (VWF) genes was examined in human liver sinusoidal endothelial cells (HLSEC/ciJ) and umbilical vein endothelial cells (EA. hy926). Methods: Activated partial thromboplastin time (APTT) and levels of FVIII:C, FVIII antigen (FVIII:Ag), and VWF antigen (VWF:Ag) were compared before and after GC treatment in patients with ITP. Changes in F8 and VWF mRNA levels in HLSEC/ciJ and EA. hy926 cells before and after dexamethasone (DEX) treatment were quantified by reverse transcription polymerase chain reaction. Changes in FVIII protein levels were also evaluated in the lysates of DEX-treated HLSEC/ciJ cells. Results: Values of APTT significantly decreased after GC treatment in ITP patients; significant increases in FVIII:C and FVIII:Ag levels were observed (p<0.05). Notably, no significant increase in VWF:Ag level was observed. F8 and VWF mRNA expressions in HLSEC/ciJ cells increased following DEX treatment (1 and 100 μM) (p<0.05), with the most significant increase seen in F8 mRNA levels (100 μM DEX; p<0.01). These increases were nullified by pretreatment with the GC receptor (GR) antagonist RU486. Additionally, VWF mRNA, but not F8 mRNA, expression increased after treating EA. hy926 cells with 1 μM DEX (p<0.05). No significant increase in FVIII protein level was observed in HLSEC/ciJ cells after treatment with 100 μM DEX. Conclusions: Direct enhancement of mRNA levels of endogenous FVIII by GC via GR activation is, at least in part, a mechanism underlying the increase in FVIII levels during GC treatment.

Musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE) is a rare connective tissue disorder. This is the first report describing the detailed and comprehensive clinical and pathophysiological features of mcEDS-DSE. The patient, with a novel homozygous nonsense variant (NM_013352.4:c.2601C>A:p.(Tyr867*)), exhibited mild skin hyperextensibility without fragility and small joint hypermobility, but developed recurrent large subcutaneous hematomas. Dermatan sulfate (DS) moieties on chondroitin sulfate/DS proteoglycans were significantly decreased, but remained present, in skin fibroblasts. Electron microscopy examination of skin specimens, including cupromeronic blue-staining to visualize glycosaminoglycan (GAG) chains, revealed coexistence of normally assembled collagen fibrils with attached curved GAG chains and dispersed collagen fibrils with linear GAG chains from attached collagen fibrils across interfibrillar spaces to adjacent fibrils. Residual activity of DS-epi1, encoded by DSE, and/or compensation by DS-epi2, a minor homolog of DS-epi1, may contribute to the mild skin involvement through this "mosaic" pattern of collagen fibril assembly.