Prevalence and treatment of chronic idiopathic thrombocytopenic purpura of childhood in Sweden

The frequency and treatment of children with chronic idiopathic thrombocytopenic purpura in Sweden were characterized using a national enquiry based on a questionnaire. Seventy-five children diagnosed as having chronic idiopathic thrombocytopenic purpura on 1 September 1993 were identified. The prevalence in children between 0.5 and 15.5 years of age was calculated to be 4.6/100 000. The median age at the time of diagnosis was 5 years and the male/female ratio was 1:1.2. Almost half of the patients (43%) were not treated at all during the disease. Steroids (43%) and intravenous immunoglobulin (25%) were most commonly used. Only two children were splenectomized.     

Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans''cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a disease with an unpredictable course and unpredictable reactivations. Since active disease may cause life-long sequelae, early detection of reactivation is important. The usefulness of erythrocyte sedimentation rate (ESR) and thrombocytosis as indicators of disease activity in patients with LCH were examined. The mean values for ESR and platelet count for each quarter of a year were compiled. The means of all the ESR estimates (n=76) during each quarter of a year with active disease was 21 mm h^-1, with intermediate disease activity 11 mm h^-1 and with resolution 7 mm h^-1. The corresponding platelet count estimates (n = 139) were 433 × 109 l^-1, 365 × 109 l^-1 and 304 × 109 l^-1, respectively. In conclusion, elevated ESR and platelet count may be clinically valuable indicators of disease activity in LCH.     

Clinical and Genetic Studies of Familial Hemophagocytic Lymphohistiocytosis in Oman: Need for Early Treatment

Hemophagocytic lymphohistiocytosis (HLH) embraces the frequently indistinguishable conditions of familial hemophagocytic lymphohistiocytosis (FHL) and virus-associated hemophagocytic syndrome (VAHS). Without therapy FHL is invariably fatal, but successful therapy, including chemotherapy and immunotherapy followed by bone marrow transplantation (BMT), has been presented. To clarify the outcome of HLH in a developing country, with regard to clinical, laboratory, and genetic features, a nationwide study on all patients diagnosed with HLH in Oman during the 5-year period 1997-2001 was performed. In 5 patients and their families, mutational analysis was made. Thirteen patients with HLH were identified, 5 of whom had clinical manifestations of central nervous system involvement at presentation. In none of the patients could an infectious cause be identified. Ten children were referred late in the disease course, and the concern about starting chemotherapy before exclusion of an acute viral infection resulted in delayed treatment in some patients. Two children were started early on the HLH-94-therapy followed by successful BMT in one child. In the successfully transplanted child, the response to intrathecal hydrocortisone appeared to be better than standard therapy with intrathecal methotrexate. Finally, a novel missense mutation in the perforin gene was identified in 2 patients and their family members, causing a transition of proline to threonine at codon 89. Early diagnosis and treatment is important to improve outcome. Intrathecal corticosteroids may be considered, in addition to intrathecal methotrexate, in certain patients. Since the novel perforin mutation has been reported in only 2 patients from Oman, and since similar polymorphism in the sequencing data of the members of their families has been identified, a founder effect is possible in this population.     

Shiga-like toxin production and connective tissue protein binding of Escherichia coli isolated from a patient with ulcerative colitis

A 15-year-old girl with her first relapse of ulcerative colitis was treated with salicylazosulfapyridine, steroids, metronidazole and parenteral nutrition for 4 weeks without significant improvement. Her faecal specimens were negative for established intestinal pathogens, but strains of Escherichia coli producing Shiga-like toxin and expressing binding of fibronectin and collagen were repeatedly isolated. Neutralizing antibodies to Shiga-like toxin were detected in serum samples. Improvement was achieved during treatment with mecillinam to which the E. coli strains were sensitive.     

Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease

Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21‐year‐old patient with fatal Epstein‐Barr virus infection–associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by >95%. Three healthy brothers carried the SH2D1A c.49G > A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. Importantly, our results highlight challenges in the clinical interpretation of SH2D1A variants and caution in using functional flow cytometry assays for the diagnosis of XLP1.     

Suicide Biomarkers to Predict Risk,Classify Diagnostic Subtypes,and Identify Novel Therapeutic Targets: 5 Years of Promising Research

BackgroundSuicide is a global health crisis. However, no objective biomarkers of suicide risk currently exist, and self-reported data can be unreliable, which limits prediction, diagnostic, and treatment efforts. Reliable biomarkers that can differentiate between diagnostic subgroups, predict worsening symptoms, or suggest novel therapeutic targets would be extremely valuable for patients, researchers, and clinicians.MethodsMEDLINE was searched for reports published between 2016 and 2021 using search terms (suicid*) AND (biomarker*) OR (indicat*). Reports that compared biomarkers between suicidal ideation, suicide attempt, death from suicide, or any suicide subgroup against other neuropsychiatric disorders were included. Studies exclusively comparing suicidal behavior or death from suicide with healthy controls were not included to ensure that biomarkers were specific to suicide and not other psychopathology.ResultsThis review summarizes the last 5 years of research into suicide-associated biomarkers and provides a comprehensive guide for promising and novel biomarkers that encompass varying presentations of suicidal ideation, suicide attempt, and death by suicide. The serotonergic system, inflammation, hypothalamic-pituitary-adrenal axis, lipids, and endocannabinoids emerged as the most promising diagnostic, predictive, and therapeutic indicators.ConclusionsThe utility of diagnostic and predictive biomarkers is evident, particularly for suicide prevention. While larger-scale studies and further in-depth research are required, the last 5 years of research has uncovered essential biomarkers that could ultimately improve predictive strategies, aid diagnostics, and help develop future therapeutic targets.     

Lipoprotein alterations and plasma lipoprotein lipase reduction in familial hemophagocytic lymphohistiocytosis.

Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities.     

Longitudinal analysis of infantile growth in children with celiac disease

The aim of the present study was to describe linear growth of infants with celiac disease, using the "ICP-growth model". Supine length during the first three years of life was studied longitudinally in 63 infants with diagnosed celiac disease. "Undisturbed" linear growth was seen during the first six postnatal months followed by reduced growth during the second half of the first year. After 1.5 years of age a pattern of catch-up growth was observed, leading to an average attained length at 3 years of age similar to that of the controls. According to the "ICP-growth model", normal linear growth can mathematically be represented during the first 3 years of life by an Infancy component with the addition of a Childhood component, the latter acting from the second half of the first postnatal year. The onset of the Childhood component (assumed to represent the age at which growth hormone begins to influence linear growth significantly) was delayed by about an average of 3 months, which is in agreement with the observed reduction in gain during the second half of the first year of life. Children suffering from celiac disease and with "late" onset of the Childhood component were shorter at 1, 2 and 3 years of age than those with "normal" onset. The results of this investigation show that ICP-based growth charts are helpful in detecting and monitoring growth for children with celiac disease, and indicate a possible mechanism whereby malabsorption (and perhaps secondary malnutrition) leads to reduced growth velocity.