Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

Endothelial specific isoform of type XVIII collagen (COL-18N): A marker of vascular integrity in haemophilic arthropathy.

BACKGROUND: Haemophilic arthropathy (HA) is a major complication in haemophilia. Collagens IV, XV and XVIII are responsible for maintaining the integrity of the vessel wall in the joint. Following joint remodelling and damage, the short isoform of collagen type XVIII (COL-18N) is degraded, releasing measurable fragments. Our goal was to quantify the specific isoform COL-18N in haemophilia A patients and to assess its relation to the clinical and radiological data as well as haemophilia joint health score (HJHS), functional independence score for haemophilia (FISH), and haemophilia quality of life (Haemo-Qol). METHODS: This cross-sectional study included 50 haemophilia A patients recruited from the Paediatric Haematology and Oncology unit, Ain Shams University, Cairo, Egypt. Quantification of COL-18N was done by ELISA. Assessment of joint state clinically using FISH and HJH scores and radiologically by X-rays and ultrasound. RESULTS: Haemophilia A patients had significantly higher median COL-18N levels compared to the control group. Inhibitor positive and negative haemophilia A patients as well as those on non-steroidal anti-inflammatory drug and those not had comparable COL-18N levels. Patients with ≥2 target joints had significantly higher COL-18N level compared to those with one or those without target joints. There were significant positive correlations between COL-18N level and the total HJHS, Haemo-Qol, the HEAD-US score and annual bleeding rate. CONCLUSION: Our results demonstrated a high level of COL-18N in haemophilia A patients and argued its benefit as a potential marker for monitoring the development of haemophilic arthropathy and tailoring the optimal treatment to prevent further joint damage.

A two-dimensional speckle-tracking echocardiography for the diagnosis of early myocardial disease in beta-thalassemia major patients.

Background: Although magnetic resonance imaging T2* is considered the gold standard to assess myocardial iron overload in ß-thalassemia patients, its routine use is limited by the high cost and limited availability. Recent data demonstrated that strain imaging by speckle tracking is a sensitive tool for early assessment of the left ventricular myocardial dysfunction. This study aims to evaluate the clinical utility of two-dimensional (2D) speckle-tracking echocardiography (STE) for the detection of early myocardial disease in beta-thalassemia major (ß-TM) patients. Materials and Methods: 2D STE, magnetic resonance imaging (MRI) heart T2* and MRI liver iron content were done for 30 ß-TM patients with no clinical heart disease, compared to 2D STE in 30 healthy age- and sex-matched controls. Results: There was a significant reduction in the longitudinal systolic strain values by STE among ß-TM patients compared to controls (P = 0.05). A longitudinal peak systolic strain cutoff values of ≤-19 was able to detect ß-TM patients having subclinical cardiac iron overload by MRI T2* (sensitivity = 90%-93.3%, specificity = 83%-100%). Mean serum ferritin in the past 2 years correlated negatively to longitudinal systolic strain values global longitudinal peak systolic strain average (P = 0.05).

COVID-19 in Children With Cancer: A Single Low-Middle Income Center Experience.

BACKGROUND: Coronavirus disease-2019 (COVID-19) could be associated with morbidity and mortality in immunocompromised children. OBJECTIVE: The objective of this study was to measure the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes. METHODOLOGY: A prospective noninterventional study including all hospitalized children with cancer conducted between mid-April and mid-June 2020 in Ain Shams University Hospital, Egypt. Clinical, laboratory, and radiologic data were collected. SARS-CoV-2 infection was diagnosed by reverse transcription polymerase chain reaction tests in nasopharyngeal swabs. RESULTS: Fifteen of 61 hospitalized children with cancer were diagnosed with SARS-CoV-2. Their mean age was 8.3±3.5 years. Initially, 10 (66.7%) were asymptomatic and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 reverse transcription polymerase chain reaction were not diagnostic; the mean absolute lymphocyte count was 8.7±2.4×109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics as per the febrile neutropenia protocol and local Children Hospital guidance for management of COVID-19 in children. CONCLUSIONS: Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swab in asymptomatic hospitalized cancer patients is recommended.

Egyptian experience in Langerhans cells histiocytosis: frequent multisystem affection and reactivation rates.

Background: Histiocytoses are unique disorders; their clinical presentations vary from self-healing lesions to life-threatening disseminated disease. Objectives: We aimed to evaluate the different clinical presentations, frequency of reactivations, and treatment outcome of Langerhans cell histiocytosis among Egyptian children. Methods: we restrospectively analyzed the data of 37 Langerhans cell histiocytosis patients (LCH) registered at Ain Shams University Children's Hospital for clinicopathological features, treatment modalities and their outcomes. Results: Twenty seven (73%) of the studied patients with LCH had multisystem disease (MS), 24 (88.9%) of them had risk organ involvement (MS RO+) and only 3 without risk organ (MS RO-). Most of the patients received LCH III protocols. Eleven patients (29.7%) had reactivations with median time till reactivation of 17 months (IQR 5-23).Reactivation rates were 40% and 50% in patients with no evidence of active disease (NAD) and those with active disease better (AD better) at week 6 evaluation respectively (p = 0.71).We report 9 deaths (all had MS RO+, two died after reactivation and 7 had progressive disease. The 5 years EFS and OS were 49.4% and 81.2% respectively. Risk stratification did not significantly affect the EFS or OS (p = 0.64 and p = 0.5 respectively). Conclusion: A high reactivation rate was encountered in children with LCH and MS-RO + irrespective of 6 weeks response to induction therapy. A high mortality in patients with progressive disease necessitates a possible earlier aggressive salvage in such group.

Silent bleeding in children and adolescents with immune thrombocytopenia: relation to laboratory parameters and health related quality of life.

Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage require attention including microscopic hematuria, fecal occult blood loss, retinal hemorrhage, and silent intracranial hemorrhage. The aim of this study was to investigate the frequency of subclinical bleeding in children with ITP and its relation to clinical and laboratory disease parameters including bleeding score and health related quality of life. This cross-sectional study included 40 ITP patients recruited from the Pediatric Hematology/Oncology unit, Children's Hospital, Ain Shams University, Cairo, Egypt. Inclusion criteria were patients with ITP (acute, persistent or chronic) having platelet count of 20,000/cmm or less at diagnosis/relapse, patients with overt bleeding and patients with secondary ITP were excluded. Occult blood in stools and urine analysis, fundus examination, and non-contrast brain MRI for microbleeds were done. Out of the forty included patients, 24 had chronic, 11 had acute and 5 had persistent ITP. Eleven patients had occult bleeds. Two patients had occult blood in stools, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Their mean age was 10.23 ± 4.18 years and their mean initial bleeding score was 2.55 ± 0.82. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. There were no significant differences between patients with occult bleeding and those without as regards the initial bleeding score, platelet counts and hemoglobin level, as well as the mean platelet counts and mean hemoglobin level over the disease duration (p > 0.5). The scoring of the parent's life, Child and parents' quality of life was low in 3 out of 11 patients with occult bleeding. There was no significant difference between patients with occult bleeding and those without as regards the ITP child and parents' quality of life items (p = 0.850 and 0.511 respectively). Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings, bleeding score, and the ITP health quality of life; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high-risk patients require additional studies.