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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.
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Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/genética , Egipto/epidemiología , Niño , Masculino , Preescolar , Femenino , Lactante , Estudios Retrospectivos , Adolescente , Resultado del Tratamiento , Manejo de la EnfermedadRESUMEN
ß-Thalassemia is one of the most common monogenetic diseases worldwide, with a particularly high prevalence in the Middle East region. As such, we have developed long-standing experience with disease management and devising solutions to address challenges attributed to resource limitations. The region has also participated in the majority of clinical trials and development programs of iron chelators and more novel ineffective erythropoiesis-targeted therapy. In this review, we provide a practical overview of management for patients with transfusion-dependent ß-thalassemia, primarily driven by such experiences, with the aim of transferring knowledge to colleagues in other regions facing similar challenges.
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Sobrecarga de Hierro , Talasemia , Talasemia beta , Humanos , Talasemia beta/terapia , Talasemia beta/tratamiento farmacológico , Talasemia/tratamiento farmacológico , Transfusión Sanguínea , Quelantes del Hierro/uso terapéutico , Prevalencia , Sobrecarga de Hierro/tratamiento farmacológicoRESUMEN
Fish parasitic diseases impose a major economic concern on aquaculture. Identified parasites of Clarias gariepinus include one monogenean, Macrogyrodactylus clarii (gills), three digeneans Orientocreadium batrachoides, Eumasenia bangweulensis and Sanguinicola sp. (intestine), two cestodes Tetracampose ciliotheca and Monobothrioides chalmersius (intestine) and two nematodes Paracamallanus cyathopharynx and Procamallanus pseudolaeviconchus (intestine and stomach). Most nematodes, digeneans and cestodes occurred in all months of the study period. However, M. clarii and Sanguinicola sp. disappeared for 6 and 8 months of the year, respectively. The digenean group was the most dominant followed by the cestode and nematode groups, respectively. The nematodes attained the highest infection rate over the digeneans and cestodes while the monogenean M. clarii recorded the lowest infection rate. The infection level of examined parasites varied seasonally, but no overall significant pattern was detected. E. bangweulensis showed a highly significant difference for all parameters seasonally. A higher prevalence was obvious in males than females for most parasites, and the opposite for the mean intensity except for P. pseudolaeviconchus which was significantly different between females and males in the mean abundance. There were variations in the relationship between the host condition factor and helminth parasite infection levels. O. batrachoides, E. bangweulensis and P. cyathopharynx recorded the highest infection level in class II. The mean prevalence was highly significantly different between host classes for T. ciliotheca, M. chalmersius and P. pseudolaeviconchus.
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Sleep disordered breathing (SDB) is a common underdiagnosed sequela of sickle cell disease (SCD) that has been linked to the frequency of vaso-occlusive crises. To determine the frequency of SDB in children with SCD and its association to SCD-related complications, thirty children and adolescents with SCD at their steady state underwent clinical, laboratory, and radiological assessment using transcranial duplex (TCD) and echo assessment of tricuspid regurge velocity (TRV). All participants had an overnight polysomnography after completing the modified STOP-Bang questionnaire. The mean age of the studied cohort was 10.2 years, with male: female ratio 1.7:1. Six children (20%) had high-risk for obstructive sleep apnea (OSA), while nine (30%) were at intermediate risk. Sleep apnea defined as apnea (AHI) > 1 event/hour was found among 18/30 (60%) subjects (14 males and 4 females). Children with AHI > 5 (moderate to severe OSA) had significantly higher TRV (p = 0.007) and left MCA flow velocity (p = 0.049) when compared to those with AHI < 5. Children with AHI > 5 were at higher risk of OSA according to the modified STOP-Bang questionnaire (p = 0.02). AHI positively correlated with TRV (r = 0.53, p = 0.003), right MCA flow velocity (r = 0.45, p = 0.013), and left MCA flow velocity (r = 0.55, p = 0.002), and negatively correlated to BMI-SDS (r = - 0.48, p = 0.008). The high frequency of OSA in the studied cohort with SCD and its association with increasing risk of PH and TCD changes highlights the importance of early detection and management of OSA in children with SCD.
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Anemia de Células Falciformes , Hipertensión Pulmonar , Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Accidente Cerebrovascular , Adolescente , Humanos , Masculino , Niño , Femenino , Estudios Transversales , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/etiología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
BACKGROUND: Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, stimulates production of reactive oxygen species. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide. AIM: To assess ET-1 gene polymorphism (G8002A) in pediatric patients with ß-thalassemia major (ß-TM) as a potential genetic marker for vascular dysfunction and its possible relation to EMAP II, oxidative stress and vascular complications. METHODS: ß-TM patients (n = 95) without symptomatic cardiac or renal disease were compared with 95 healthy controls. Markers of hemolysis, serum ferritin, urinary albumin-to-creatinine ratio, serum EMAP II, malondialdehyde (MDA) and antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase and catalase were measured. ET-1 gene polymorphism (G8002A) was determined using polymerase chain reactionrestriction fragment length polymorphism. RESULTS: ß-TM patients had significantly higher EMAP II than healthy controls. EMAP II was significantly higher among patients with cardiac disease, pulmonary hypertension (PH) risk, nephropathy, poor compliance to therapy and ferritin ≥ 2500 µg/L. There were significant correlations between EMAP II and transfusion index, LDH, ferritin and oxidative stress markers. The AA genotype of ET-1 gene polymorphism (G8002A) was significantly higher among ß-TM patients than controls. The number of patients with cardiac disease, PH risk or nephropathy was significantly higher among AA genotype compared with GG and GA genotypes. Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD and GPx were significantly higher in AA genotype. CONCLUSION: ET-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with ß-TM.
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Endotelina-1 , Proteínas de Unión al ARN , Talasemia beta , Niño , Humanos , Talasemia beta/genética , Talasemia beta/complicaciones , Talasemia beta/terapia , Endotelina-1/genética , Ferritinas , Marcadores Genéticos , Cardiopatías/complicaciones , Polimorfismo Genético , Superóxido Dismutasa , Enfermedades Renales , Proteínas de Unión al ARN/genéticaRESUMEN
BACKGROUND: Platelet glycoprotein VI (GPVI) receptor is essential for platelet adhesion and aggregation. Eltrombopag is as an effective treatment for chronic immune thrombocytopenia (ITP); yet, its effect on platelet function is not fully characterized. AIM: This prospective study investigated the effect of eltrombopag therapy on platelet function through assessment of GPVI receptor expression and soluble GPVI levels among pediatric patients with persistent or chronic ITP. METHODS: Thirty-six children and adolescents with persistent or chronic ITP were divided equally into two groups either to receive eltrombopag therapy or the standard of care. All patients were followed-up for 12 months with assessment of bleeding score and complete blood count (CBC). Evaluation of GPVI expression using flow cytometry and measurement of its soluble form by ELISA was done at baseline and at 6 months. RESULTS: ITP patients on eltrombopag had significantly lower bleeding score after 6 months of therapy while the quality of life has significantly improved. Platelet count was significantly increased throughout the study. GPVI expression by flow cytometry and soluble GPVI levels were significantly increased after eltrombopag therapy. After 12 months, ITP patients on eltrombopag were able to maintain a good quality of life and low bleeding score. CONCLUSION: Our data suggest that eltrombopag, through its effect on the GPVI receptor expression and its soluble form, might reduce bleeding manifestations and improve the quality of life of chronic and persistent ITP children independent of its effect on the platelet count.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adolescente , Humanos , Niño , Estudios Prospectivos , Calidad de Vida , Glicoproteínas de Membrana Plaquetaria , HemorragiaRESUMEN
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.
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Colágeno Tipo XVIII , Hemartrosis , Hemofilia A , Enfermedades Vasculares , Adolescente , Vasos Sanguíneos/fisiopatología , Niño , Colágeno Tipo XVIII/sangre , Estudios Transversales , Femenino , Hemartrosis/sangre , Hemartrosis/etiología , Hemofilia A/sangre , Hemofilia A/complicaciones , Humanos , Masculino , Isoformas de Proteínas/sangre , Calidad de Vida , Enfermedades Vasculares/sangre , Enfermedades Vasculares/etiologíaRESUMEN
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).
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Few case reports and series reported abdominal lymphadenopathy (ALN) in people with Gaucher disease (GD). However, it's prevalence among Gaucher population, clinical implications and potential biomarkers are unknown. Hence this study aims to assess the prevalence of ALN among children with GD & to correlate it to neutrophil-lymphocytic-ratio (NLR), platelet-lymphocytic-ratio (PLR) and glucosylsphingosine (Lyso-GL1). Fifty children with GD (14 type-1 and 36 type-3) on enzyme-replacement therapy (ERT) were compared to 50 matched healthy controls, focusing on history of pressure manifestations by ALN (diarrhea, constipation, abdominal pain, intestinal obstruction), and history of splenectomy, with calculation of severity scoring index (SSI). NLR, PLR and Lyso-GL1 were measured. Abdominal-ultrasound was done with assessment of liver and spleen volumes and ALN. CT-scan was done for those having significant lymphadenopathy. Twenty-six children with GD had ALN (52%). The most common presentations were abdominal-pain (22%) & constipation (18%), with intestinal-obstruction in 3 children (6%). Children with GD had significantly higher NLR (p < .001) and decreased PLR (p = .024) compared to controls. Interestingly, children with GD having ALN had significantly higher SSI (.012), Lyso-GL1 (p = .002) and NLR (p = .001) than those without ALN. Multivariate-logistic regression showed that ALN was independently related to Lyso-GL1 (p = .027), NLR (p = .023) and SSI (p = .032). Thus, ALN is a prevalent GD morbidity with wide clinical-spectrum ranging from asymptomatic cases to intestinal obstruction. ALN is related to SSI, NLR and Lyso-GL1 in children with GD.HighlightsChildren with GD had significantly higher NLR and lower PLR compared to controls.Children with GD having ALN had significantly higher SSI, Lyso-GL1 and NLR than those without ALN.ALN was independently related to Lyso-GL1, NLR and SSI in children with GD.
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Enfermedad de Gaucher , Obstrucción Intestinal , Linfadenopatía , Biomarcadores , Niño , Estreñimiento , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/epidemiología , Humanos , Linfadenopatía/etiología , Psicosina/análogos & derivados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Outcome of childhood acute lymphoblastic leukemia (ALL) in low- and middle-income countries is lagging in many aspects including diagnosis, risk stratification, access to treatment and supportive care. OBJECTIVE: to report the outcome of childhood ALL at Ain Shams University Children's Hospitals with the use of risk-based protocols before the implementation of minimal residual disease technology and to evaluate the use of double delayed intensification (DDI) in standard risk patients. METHODS: Two hundred and twenty patients with ALL diagnosed between January 2005 and December 2014 were included in the study. Patients were treated according to a modified CCG 1991 and 1961 for standard and high risk respectively. Patients were stratified into three risk groups: standard risk (SR), high-risk standard arm (HR-SA), and high-risk augmented arm (HR-AA). RESULTS: Among the whole cohort, the 10-year event-free survival (EFS) and overall survival (OS) were 78.1% and 84.3% respectively. Patients with Pre-B immunophenotype (IPT) had significantly better outcome than T-cell IPT (EFS 82.0% versus 58.6%, p < 0.001; OS 86.9% versus 69%, p = 0.003 for Pre-B and T-cell respectively). Among the SR group, patients treated with single delayed intensification (SDI) had comparable EFS and OS rates when compared to patients treated with DDI with EFS 82.4% versus 87.5%, p = 0.825 and OS 88.2% versus 93.5%, p = 0.638 for SDI and DDI groups, respectively. CONCLUSION: The use of risk-based protocol with simple laboratory techniques resulted in acceptable survival outcome in resource limited settings. The use of double delayed intensification showed no survival advantage in patients with standard risk.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Lactante , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Pronóstico , Medición de Riesgo , Resultado del TratamientoRESUMEN
Hearing impairment is a reported complication of sickle cell disease, yet inner ear pathology is not fully understood. The study purpose was to examine the patterns of inner ear involvement in patients with sickle cell disease by magnetic resonance imaging (MRI) and to assess its association with auditory functions. A cross-sectional study included 22 children with sickle cell disease examined for inner ear pathology by audiogram, MRI inner ear and transcranial Doppler (TCD) with revision of their hospital records for transfusion, chelation and hydroxyurea (HU) therapy. Abnormal MRI in the form of intrinsic T1 hyperintensity within the lumen of inner ear structures and cochlear neuropathy was found in five (22.7%) patients; left middle cerebral artery (MCA) flow velocity was higher in patients with abnormal MRI (83.4 ± 5.3 cm/sec) compared to normal MRI (68.2 ± 11.1 cm/sec) (p = 0.015), however, none of the patients had TCD of >170 cm/sec. There was no significant difference between patients with normal and abnormal MRI as regards hearing level and speech audiometry. Sensorineural hearing loss (SNHL) was present in two (9.1%) and conductive hearing loss (CHL) in two (9.1%) patients. There was a significant negative correlation between right ear mean hearing level and right MCA flow velocity and significant negative correlation between left ear mean hearing level and basilar artery (BA) flow velocity. We concluded that inner ear pathology is not uncommon in asymptomatic patients with sickle cell anemia, yet it did not correlate with hearing impairment and may occur with normal TCD results.
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Anemia de Células Falciformes/complicaciones , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/etiología , Adolescente , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Biomarcadores , Niño , Oído Interno/diagnóstico por imagen , Oído Interno/patología , Oído Interno/fisiopatología , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pruebas Auditivas , Humanos , Imagen por Resonancia Magnética , Masculino , Evaluación de Síntomas , Ultrasonografía Doppler Transcraneal , Vestíbulo del Laberinto/patologíaRESUMEN
BACKGROUND: Patients with Gaucher disease (GD) have an increased risk for parkinsonism. Retinal thinning has been described in parkinsonism as an early nonmotor feature. Scarce reports have addressed retinal thickness changes in GD. OBJECTIVES: The objectives of this study were to compare ganglion cell complex (GCC) thickness in adolescents and young adults (AYAs) with GD with healthy control subjects, and to correlate it with the presence of parkinsonian features (PFs), clinical prodromal markers of parkinsonism, severity score index (SSI), and glucosylsphingosine (Lyso-GL-1). METHODS: This study included 48 AYAs with GD (11-29 years), 11 with manifest PFs (Group 1) and 37 with no PFs (Group 2), and 48 matched healthy control subjects (Group 3). Age of GD onset, disease duration, medication history, history of constipation, SSI, and hematological assessment were done. Neurocognitive evaluation included Parts I, II, and III of the Unified Parkinson's Disease Rating Scale (UPDRS), Wechsler Adult and Intelligence Scale and Wechsler Intelligence Scale for Children, Beck Depression Inventory (BDI), rapid eye movement sleep behavior disorder (RBD) scale, Munich Parasomnia Screening scale, and the olfactory dysfunction scale. Molecular analyses of the acid GBA gene and Lyso-GL-1 were done. Participants underwent full ophthalmological examination and optical coherence tomography with GCC thickness measurement. RESULTS: GCC was significantly thinner in Group 1 than in Groups 2 and 3 (P < 0.001), whereas no significant difference was found between Groups 2 and 3 (P = 0.977). In addition, a significant interocular GCC thickness difference was found among the studied AYAs with GD (P = 0.007). GCC correlated positively with total intelligence quotient (P < 0.001) and negatively with Lyso-GL-1 (P = 0.019), UPDRS (P = 0.004), and BDI (P = 0.029), but not with SSI (P = 0.874), GD type (P = 0.85), or genotype (P = 0.842). A significant negative relationship was found between GCC thickness and PFs (P = 0.001), parasomnia (P = 0.003), constipation (P = 0.031), RBD (P = 0.044), and hyposmia (P = 0.033). CONCLUSIONS: GCC thinning may be a promising biomarker for central nervous system neurodegeneration that has the potential to monitor early PFs among people with GD. © 2020 International Parkinson and Movement Disorder Society.
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Enfermedad de Gaucher , Trastorno de la Conducta del Sueño REM , Adolescente , Biomarcadores , Niño , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/genética , Humanos , Trastorno de la Conducta del Sueño REM/etiología , Retina , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
BACKGROUND: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. OBJECTIVES: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. METHODS: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. RESULTS: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001). CONCLUSIONS: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.
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Diagnóstico por Imagen de Elasticidad , Enfermedad de Gaucher , Niño , Enfermedad de Gaucher/diagnóstico por imagen , Enfermedad de Gaucher/patología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Progranulinas , Índice de Severidad de la EnfermedadRESUMEN
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.
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Histiocitosis de Células de Langerhans/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/complicaciones , Niño , Preescolar , Cladribina/administración & dosificación , Ciclosporina/administración & dosificación , Progresión de la Enfermedad , Egipto , Femenino , Histiocitosis de Células de Langerhans/mortalidad , Histiocitosis de Células de Langerhans/fisiopatología , Humanos , Lactante , Células de Langerhans/patología , Hígado/efectos de los fármacos , Hígado/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/fisiopatología , Masculino , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Evidence about the link between glucocerebrosidase (GCase) and parkinsonism is growing. Parkinsonism was described in adult type 1 Gaucher disease (GD); few case reports described it in type 3GD. To assess the presence of parkinsonian features in a cohort of Egyptian GD patients and correlate these findings to their genotype, phenotype, severity scoring index (SSI), cognitive function, and the presence of depressive symptoms. Twenty-four GD patients from the Pediatric Hematology Clinic, Ain Shams University, were assessed for medication history, neurological symptoms, depressive symptoms, and family history of parkinsonism. Anthropometric measures, complete neurological assessment, and SSI were examined. Neuropsychiatric evaluation included parts I, II, III, and V of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Wechsler Intelligence Scale for Children (WISC-children). Molecular analysis of the acid GBA gene was performed, and SSI was calculated. Sixteen GD patients (66.6%) had parkinsonian features with a male to female ratio of 1:1. Their mean age was 15.69 ± 5.62 (range, 12-26). They were all on enzyme replacement therapy (ERT) with a dose of 60 U/kg/2 weeks. Twelve GD patients were phenotypically type 3 (75%). Thirteen GD patients with parkinsonian features (81.25%) had L483P mutation. GD patients with parkinsonian features had higher SSI (P < 0.001), lower cognitive functions (P = 0.007), and more significant depressive symptoms (P = 0.031). Logistic regression analysis revealed that GD genotype (P = 0.003), GD type (P = 0.006), and cognitive functions (P = 0.03) were the only significant independent factors for the development of parkinsonian features among GD patients. With the increased life span and improved somatic manifestations of type 3GD on ERT, these patients can live to develop parkinsonism. Cognitive decline and depression can be early predictors of parkinsonism among GD population.
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Trastornos del Conocimiento/complicaciones , Depresión/psicología , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/diagnóstico , Trastornos Parkinsonianos/complicaciones , Adolescente , Adulto , Antropometría , Niño , Trastornos del Conocimiento/psicología , Estudios de Cohortes , Estudios Transversales , Egipto/epidemiología , Femenino , Enfermedad de Gaucher/psicología , Genotipo , Glucosilceramidasa/genética , Humanos , Masculino , Mutación , Trastornos Parkinsonianos/psicología , Fenotipo , Índice de Severidad de la Enfermedad , Escalas de Wechsler , Adulto JovenRESUMEN
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.
Asunto(s)
Hemorragia/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Calidad de Vida , Adolescente , Factores de Edad , Enfermedades Asintomáticas , Niño , Preescolar , Estudios Transversales , Egipto , Femenino , Hemorragia Gastrointestinal/etiología , Hematuria/etiología , Hemorragia/diagnóstico , Humanos , Hemorragias Intracraneales/etiología , Masculino , Sangre Oculta , Púrpura Trombocitopénica Idiopática/diagnóstico , Hemorragia Retiniana/etiología , Medición de Riesgo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Although pulmonary involvement is important orbidity in Gaucher disease (GD), it is previously reported to be rare. Moreover, no epidemiological studies described its prevalence specifically in children. The clinical spectrum and risk determinants for this complication and its long-term response to therapy are unknown. AIM: To assess the prevalence of clinical and radiological pulmonary involvement in pediatric GD patients and its relation to Gaucher severity and genotype. METHODS: Forty-eight GD patients were studied focusing on pulmonary and neurological manifestations with assessment of severity scoring index (SSI; a Gaucher specific scale). Detailed enzyme replacement therapy (ERT) history was taken regarding dose, duration, and effect on pulmonary manifestations. Genotype was performed to 30 patients. Radiological investigations included plain chest-radiography (CXR), high-resolution CT (HRCT), and hepatic and splenic volumes. RESULTS: Fifteen patients had type 1 (31.2%) and 33 patients had type 3 GD (68.8%). The most common mutation was L483P detected in 25 patients (83.3%). Sixteen patients had recurrent chest wheeze (33%). CXR showed pulmonary findings in 17 patients (35.4%) while HRCT-chest showed affection in 31 patients (64.6%). The ground-glass pattern was present in 14 patients (29.1%), reticulonodular infiltration in 9 patients (18.8%), air trapping in 6 patients (12.5%), and bronchiectatic changes in two patients (4.2%). Univariate logistic regression analysis for predictors of abnormal HRCT-chest was negatively correlated with platelets (P = .01) and hemoglobin (P = .018) and positively correlated with recurrent chest wheezing (P = .019), abnormal CXR (P = .007), and SSI (P = .009). CONCLUSION: Pulmonary involvement is a prevalent morbidity of GD with variable presentations. CXR for early detection of pulmonary involvement in GD is safe and highly predictive.
Asunto(s)
Enfermedad de Gaucher , Adolescente , Adulto , Niño , Preescolar , Terapia de Reemplazo Enzimático , Femenino , Enfermedad de Gaucher/diagnóstico por imagen , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/genética , Estudios de Asociación Genética , Glucosilceramidasa/uso terapéutico , Humanos , Lactante , Pulmón/diagnóstico por imagen , Masculino , Mutación , Radiografía , Ruidos Respiratorios , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.
Asunto(s)
Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Hemoglobinas/análisis , Neoplasias/complicaciones , Reticulocitos , Anemia Ferropénica/tratamiento farmacológico , Niño , Preescolar , Eritropoyesis/efectos de los fármacos , Femenino , Humanos , Compuestos de Hierro/uso terapéutico , Masculino , Reticulocitos/efectos de los fármacosRESUMEN
OBJECTIVES: Gaucher disease (GD) may include psychiatric symptoms as a part of its wide spectrum of manifestations, with several reports describing its association with mood or psychotic symptoms. We investigated the presence of psychiatric manifestations in an Egyptian sample of Gaucher Disease (GD) patients. METHODS: Our sample consisted of 22 GD patients (diagnosed by low glucocerebrosidase (GBA) activity in leukocytes or fibroblasts and molecular analysis by full (GBA) gene sequencing). 13 patients were classified as GD type 1 and 9 patients as GD type 3. We assessed the presence of psychiatric symptoms using the Mini-international neuropsychiatric interview (M.I.N·I) and the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) tools. Arabic versions were used. RESULTS: The results showed that 41% of the sample had psychiatric disorders, with the most common being depression. None was receiving any form of psychiatric treatment. We found no statistically significant association between the presence of psychiatric disorders and any of the clinical variables of GD, its phenotype, or genotype. CONCLUSION: The current results suggest that GD patients are susceptible to psychiatric disorders. However, these results need to be replicated on a wider scale. These findings are of ultimate importance, considering the lack of integrated services addressing both the medical and psychological aspects of inborn errors of metabolism in many countries.
Asunto(s)
Terapia de Reemplazo Enzimático/métodos , Enfermedad de Gaucher/psicología , Trastornos Psicóticos/etiología , Adolescente , Niño , Estudios Transversales , Egipto , Femenino , Enfermedad de Gaucher/tratamiento farmacológico , Humanos , Masculino , Trastornos Psicóticos/tratamiento farmacológicoRESUMEN
BACKGROUND: Surfactant protein D (SP-D) is considered a candidate biomarker for lung integrity and for disease progression. AIM: We determined the level of SP-D in children and adolescents with SCD and assessed its possible relation to pulmonary complications and lung function. METHODS: Serum SP-D levels were assessed in 50 SCD patients compared with 30 healthy controls. High-resolution computerized tomography (HRCT) of the chest was done. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1 ), FEV1 /FVC% and forced expiratory flow rate during 25-75% of expiration (FEF25-75%) were determined. RESULTS: SP-D was significantly higher in SCD patients than controls, particularly patients with sickle cell anemia than those with sickle ß-thalassemia. SP-D levels were significantly associated with increasing severity of interstitial lung disease. The highest SP-D levels were observed among patients with restrictive lung disease followed by mixed type then obstructive lung disease. SP-D was positively correlated to HbS and serum ferritin while negatively correlated to duration of hydroxyurea treatment and parameters of pulmonary functions. ROC curve analysis revealed that SP-D cutoff value 720 ng/mL could significantly detect the presence of abnormal pulmonary function among SCD patients with 82% sensitivity and 88% specificity. Logistic regression analysis showed that SP-D is an independent factor related to abnormal pulmonary function in SCD. CONCLUSIONS: SP-D may be a promising biomarker for screening of SCD patients for risk of later pulmonary complications.