Autoimmune cytopenias in children: When to think of primary immunodeficiency?

Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.

Knowledge, attitudes, and practices of the ethics in medical research among Moroccan interns and resident physicians.

BACKGROUND: In Morocco, medical research ethics training was integrated into the medical curriculum during the 2015 reform. In the same year, a law on medical research ethics was enacted to protect individuals participating in medical research. These improvements, whether in the reform or in the enactment of the law, could positively impact the knowledge of these researchers and, consequently, their attitudes and practices regarding medical research ethics. The main objective of this work is to assess Moroccan physicians' knowledge, attitudes, and practices at the beginning of their careers (interns and residents) in medical research ethics. PATIENTS AND METHODS: This is a multicenter cross-sectional study conducted in 2021 among Moroccan physicians. Three scores were created and validated to assess physicians' level of knowledge, attitudes, and practices regarding research ethics. A descriptive analysis was carried out, followed by a univariate analysis and a multivariate analysis using multivariate binary logistic regression to study the factors associated with the different calculated scores. RESULTS: A total of 924 physicians were included in the study, with an average age of 27.8 ± 2.2 years. 40.7% had a high medical research ethics knowledge score, and 68.8% had good attitudes. These two scores were positively associated with age and were statistically higher in residents and in physicians who had received training in medical research ethics during their medical curriculum. Only 29,9% of physicians who had participated in research studies had adequate practices with medical research ethics. This score was statistically higher in residents and in physicians who had heard about research ethics. CONCLUSION: A genuine introduction to ethics in the medical curriculum is essential to enhance researchers' knowledge, attitudes, and practices. This, in turn, can lead to an increase in both the quantity and quality of research conducted in Morocco.

Gluten-Free Diet Compliance in Children With Celiac Disease and Its Effect on Clinical Symptoms: A Retrospective Cohort Study.

A gluten-free diet (GFD) is the only scientifically proven treatment for celiac disease (CD). Strict adherence to this diet in children yields excellent results in terms of the clinical symptoms present at the time of diagnosis. Despite the constraints associated with following this diet, it remains the only hope for children with CD to have a better quality of life and life expectancy. METHODS: A retrospective descriptive cohort study was carried out on children diagnosed with CD in the pediatrics department of the Hassan II University Hospital in Fez, Morocco. The children were followed up for 18 months, during which time they were seen as outpatients at different frequencies depending on their clinical condition and degree of compliance with the diet. RESULTS: Only half of the diagnosed children continued to follow our structure. Compliance with the gluten-free diet varied from 58.7% (n = 84) of children who strictly followed the GFD to 3.5% (n = 5) of children who never followed the diet. Compliance was significantly correlated with the child's age, with adolescents being the least compliant (p = 0.03). Similarly, a correlation was observed between compliance with the diet and the disappearance of symptoms (p <0.01), the persistence of certain symptoms (p = 0.02), and the occurrence of complications (p = 0.01). The majority of children (87.3%) had their clinical symptoms resolved within a mean delay of 6.4±3.6 months, with a mode of three months. The speed of symptom resolution differed from one symptom to another but remained statistically correlated with the degree of GFD compliance (p = 0.03). CONCLUSION: Despite the excellent results of a GFD on clinical symptoms in children, the discrepancies observed between compliance and non-compliance call for close follow-up of children with CD to avoid complications and repercussions on the vital prognosis in adulthood.

Celiac Disease in Moroccan Children: Diagnostic Characteristics and Determinants of Diagnosis Delay.

Advances in the field of celiac disease have led to a better understanding of the disease, but it remains underdiagnosed and poses a daily challenge to clinicians to make a timely diagnosis. This study aims to analyze and describe diagnosis characteristics, diagnosis delay, and the factors influencing this delay in Moroccan children. Our study included 324 children diagnosed during the study period from January 01, 2010, to December 30, 2019, at the Department of Pediatrics, Hassan II University Hospital in Fez, Morocco. Data were collected using a collection grid and then analyzed using SPSS 26 software (IBM Corp., Armonk, NY). The results showed a female predominance (n=197, 60.8%), with a diagnosis age of 73.8±46.8 months. The mean age onset of symptoms was 51.3±41.2 months, and the diagnosis delay was 22.2±22.6 months, with only 32.7% (n=106) diagnosed less than 12 months after symptom onset. The most common consultation reason was diarrhea (n=149, 46%) and growth delay (n=105, 32.4%) and 50.5% (n=98) of parents consulted a pediatrician first. The three clinical, serologic, and histologic criteria made it possible to agree on the diagnosis, with the clinical profile dominated by the digestive form at 84.9% (n=279), serologic with the presence of IgA transglutaminase antibodies (95.7%; n=310), and histologic with villous atrophy at 91.7% (n=297). Unfortunately, 14.8% (n=48) of the children were diagnosed with a celiac crisis. The multivariate logistic regression analysis showed that as symptoms onset age increased, so did the risk of late diagnosis (OR=0.96, 95% CI: 0.94 to 0.97, p<0.001). Age of diagnosis was also associated with delayed diagnosis (OR=19.68, 95% CI: 8.77 to 44.15, p<0.001). The combination of these variables and the diagnosis delay argues in favor of adopting a diagnosis strategy that includes raising awareness among healthcare professionals of the need to identify typical and atypical cases early in order to reduce the adverse effects of late diagnosis and the complications that can result. This methodology for improving diagnoses may also unearth previously unknown aspects of celiac disease in Moroccan children.

Moroccan Children With Helicobacter pylori Infection: Demographics, Clinical Features, and Histological Findings.

BACKGROUND: Infesting nearly half of the world's population, Helicobacter pylori is thought to cause peptic ulcers and gastric adenocarcinoma. Several studies have examined the association between H. pylori and socioeconomic, clinical, and histological factors in pediatric populations. Similarly, this study aimed to describe the characteristics of H. pylori infection in Moroccan children. METHODS: Patients aged 1-17 years who underwent upper gastrointestinal endoscopy over a period of two years from January 2019 to January 2021 were included in this study. Gastric biopsies from the antrum and corpus of the stomach were collected. Detection of H. pylori infection was confirmed by Giemsa stain. Demographic data and clinical and endoscopic characteristics were collected and histopathological findings with gastritis scoring were recorded according to the Sydney System. RESULTS: In 213 children, 95 (45%) were found to be infected with H. pylori, and the infection rates increased as the children aged. While no significant relationship between the infection of H. pylori and all symptoms was founded, a significant association was found in nodular gastritis (p<0.05), and 98% of the infected children had chronic inflammation, which was active in 22% and atrophic in 47%. The atrophy and activity were absent or mild, and the inflammation was mild to moderate. CONCLUSION: According to this study, nodular gastritis and nonspecific symptoms were related to H. pylori infection in Moroccan children. In addition, the association between this disease and gastric atrophy in our study needs the monitoring of the mucosa of Moroccan children with gastritis and identifying factors that may contribute to gastric cancer.

[Reversible central pontine myelinolysis without hyponatremia in a child with acute lymphoblastic leukemia: a case report]. / Myélinolyse centropontine réversible sans hyponatrémie chez un enfant atteint de leucémie aigüe lymphoblastique: à propos d'un cas.

Central pontine myelinolysis is a demyelinating disorder mainly affecting the central pons. In some cases, it is associated with extrapontine myelinolysis. It is usually caused by rapid correction of hyponatremia and osmotic shock. We here report the case of a 3.5-year-old girl diagnosed with acute lymphoblastic leukemia admitted to our Oncology Unit with neutropenic fever and diarrhea. Laboratory tests showed mild neutropenia, normochromic normocytic anemia. Electrolyte tests were normal without hyponatremia. She received antibiotic therapy with Metronidazole. Five days later, she developed flaccid quadriparesis with mutism. Computerized tomography (CT) scan was normal, cerebrospinal fluid (CSF) examination was normal (there was no evidence of leukemic cells) and ophthalmological examination did not show any abnormalities. Brain MRI found hyperintense signal in the pons. The child improved without specific treatment, and clinical and complete neurological recovery was noted. This case highlights that myelinolysis can occur under some circumstances not related with hyponatremia such as malignancy, chemotherapy.

[Sepsis outbreak associated with use of contaminated propofol: A new case series and literature review]. / Complications infectieuses liées à l'utilisation du propofol : une nouvelle série de cas et revue de la littérature.

INTRODUCTION: Propofol is the most commonly used hypnotic agent for the induction and maintenance of general anesthesia. Due to its lipid-based composition, propofol requires a strict handling protocol to avoid an increased risk of extrinsic contamination. METHODS: On September 09, 2021, 05 patients with post-anaesthetic Enterobacter cloacae infections were identified in the pediatric exploration department of the Hassan II University Hospital of Fez in Morocco. We describe the investigation into this outbreak. All patient medical records were reviewed to determine patient characteristics and potential risk factors. For the literature review, we identified relevant articles by searching PubMed, Medline, Embase and Science Direct. RESULTS: Our study included five patients, 80% were boys. The average age was 4.6 years (1-7 years), with no medical history. All five patients underwent exploratory procedures. Immediately after the procedures, all 5 patients presented with chills, tachycardia and fever in the same order of admission. They were all admitted to hospital and blood samples were taken. Blood cultures were positive for E. cloacae. All patients had elevated levels of C-reactive protein (CRP) and an elevated white blood cell count. Bacteriological investigation revealed that the infection was caused by extrinsic contamination of the intravenous anesthetic propofol by E. cloacae. CONCLUSION: Fatal infections due to contaminated drugs, including propofol, have been reported worldwide. Propofol is a potential source of infections due to its lipophilic nature which promotes microbial growth. This probably remains an underestimated problem that deserves awareness for early recognition.

The high sensitivity and specificity of rapid urease test in diagnosis of Helicobacter pylori infection in Moroccan children.

Background and Objectives: Infesting nearly 50% of the world's population, Helicobacter pylori are thought to cause peptic ulcers, as well as gastric adenocarcinoma. Several diagnostic methods are available to detect this bacterium; however, at least two must be used together for an accurate diagnosis. This study evaluated the use of rapid urease test for diagnosis of H. pylori infection in a pediatric population. Materials and Methods: Five gastric biopsies were taken from children during a 2-year period for the purpose of histological, molecular, bacteriological culture, and rapid urease testing. Results: Among 83 children, 38 were male, and 45 were female with an age ranging of 2 to 15 years. The infected group represented 31%. The rapid urease test had a sensitivity of 88.5%, a negative predictive value of 94%, a specificity of 84.2%, and a positive predictive value of 72%. Conclusion: A rapid urease test may be appropriate for ruling out H. pylori infection after a negative result. The positive results however, may be confirmed by a second invasive test.

Rapunzel syndrome complicated with pancreatitis, intussusception and intestinal perforation.

We report a case of a 4-year-old girl with limited financial resources, a background history marked by chronic abdominal discomfort and a positive Helicobacter pylori stool antigen test. The child presented with pallor, striking epigastric pain, nausea and vomiting. Blood tests reported high serum lipase levels. Investigations showed proof of nodular gastritis, intussusception and mild acute pancreatitis. The surgical procedure revealed Rapunzel syndrome complicated with intussusception and intestinal perforation, successfully treated. The postoperative course went uncomplicated.

Intraspecific genetic variability in a population of Moroccan Leishmania infantum revealed by PCR-RFLP of kDNA minicircles.

In Morocco, Leishmania infantum is the main etiologic agent of human and canine visceral leishmaniasis (VL). This species has been proven to be an opportunistic agent in HIV+ patients and is also responsible of sporadic cutaneous leishmaniasis (CL).This work aims to evaluate the genetic variability of Moroccan L. infantum strains based on PCR-RFLP analysis of the kinetoplastid DNA (kDNA) minicircles. A total of 75 DNA samples extracted from positive Giemsa-stained smears (n=32) and from L. infantum cultures (n=43) was studied. The samples have been taken from VL patients infected (n=7) or not (n=56) by HIV, patients with CL (n=2) and finally from infected dogs (n=10). An hypervariable region of kDNA was amplified using the primers MC1 and MC2; the PCR products were digested separately by a panel of nine restriction enzymes. The presence or absence of restriction fragments was scored in a binary matrix and the SplitsTree4 software was used for the construction of a Neighbor-Net network. Moroccan L. infantum population showed an important level of variability with the identification of 6 genotypes. For each genotype a PCR product was sequenced, confirming the presence of all the expected restriction sites. The predominant profile was the genotype B. A new genotype, named Q was detected for the first time, whereas the four other genotypes (G, K, N and O) were reported sporadically in the Mediterranean basin. The Neighbor-Net network segregates our L. infantum population into 3 clusters: Cluster I includes genotype B, cluster II grouping the genotypes O, Q and G and finally the cluster III contains the genotype N. The kDNA-PCR-RFLP assay is suitable for use directly on biological samples; it reveals an important degree of genetic variability among L. infantum strains even those belonging to the same zymodeme what is of great epidemiological interest.

Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases).

Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified.

The TLR2 and TLR4 gene polymorphisms in Moroccan visceral leishmaniasis patients.

Visceral leishmaniasis (VL) is endemic in the Mediterranean basin and leads to the most severe form of Leishmania infection, lethal if left untreated. However, most infections are sub-clinical or asymptomatic, reflecting the influence of host genetic background on disease outcome. This study aimed to investigate possible association of TLR4 Asp299Gly, TLR4 Thr399Ile and TLR2 Arg753Gln polymorphisms with VL in Moroccan children. We enrolled 119 children with VL caused by Leishmania infantum as well as 138 unrelated children, 95 asymptomatic subjects and 43 healthy individuals who had no evidence of present or past infection. Polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system assay (ARMS-PCR). Results showed significant differences in genotype Thr399Ile and recessive model frequencies between VL and delayed-type hypersensitivity (DTH+) groups (p=0.018, OR=0.414CI 0.195-0.880; p=0.029, OR=0.448CI 0.214-0.938], respectively) by having the amino-acid threonine polymorphism as a reference in the VL group. Concerning the Asp299Gly there were a significant associations when comparing VL vs DTH+ (Asp299Gly genotype p=0.002, OR=0.326CI 0.158-0.671, allele frequencies p=0.033, OR=0.396CI 0.164-0.959, recessive model p=0.002, OR=0.343CI 0.172-0.681) and DTH+ vs DTH- groups (Asp299Gly genotype p=2.160E-4, OR=3.065CI 1.672-5.618, Gly299Gly genotype p=0.047, OR=0.368CI 0.299-0.452, allele frequencies p=1.406E-7, OR=29.571CI 3.907-223.8, recessive model p=4.370E-14, OR=36.965CI 8.629-158.3), by having the aspartic acid polymorphism as a reference these results suggest that the allele A (savage) confer protection against the clinical manifestations but not against the infection. Furthermore, there was a significant association regarding the Arg753Gln genotype (p=0.002, OR=0.326CI 0.158-0.671), allele frequencies (p=0.033, OR=0.396CI 0.164-0.959) and when applying a recessive model (p=0.002, OR=0.343CI 0.172-0.681) in the VL vs DTH+ groups. The same results was observed when comparing DTH+ vs DTH- groups (p=4.136E-6, OR=0.211CI 0.104-0.428), allele frequencies (p=0.008, OR=0.327CI 0.137-0.779) and recessive model (p=1.748E-5, OR=0.244CI 0.124-0.480). The results provide evidence that allele C in Thr399Ile and allele G in Arg753Gln polymorphisms may lead to protection against the clinical disease. Our data provide insights into the possible role of TLR2 and TLR4 variations in VL susceptibility.

The first PTPN1 1 mutations in hotspot exons reported in Moroccan children with Noonan syndrome and comparison of mutation rate to previous studies.

BACKGROUND/AIM: Noonan syndrome is an autosomal dominant disorder with an incidence of 1/1000-2500. It results from protein-tyrosine phosphatase, nonreceptor type 11 (PTPN11) mutations in roughly 50% of cases. Mutational screening of PTPN11 has been carried out in different populations. Thus, the aim of this study was to screen, for the first time, PTPN11 mutations in a series of Moroccan Noonan syndrome patients. MATERIALS AND METHODS: We used bidirectional sequencing of exons 3 and 8, considered as PTPN11 mutation hot spots, and then compared the rate of mutational events of these exons between different populations using chi-square and Fisher's exact tests. RESULTS: We detected 3 heterozygous mutations (Asp6lGly, Tyr63Cys, and Asn308Ser) in 4 individuals of 16 sporadic patients (25%). The rate of mutation in our cohort did not differ from that of other populations. However, we found significant differences in the mutation rate of exon 8 between one Japanese cohort and some populations, which requires more investigations to be explained. CONCLUSION: The present study allowed identification of mutations clustered in exons 3 and 8 of the PTPN11 gene in a Moroccan Noonan syndrome cohort and enabled us to give appropriate genetic counseling to the mutation-positive patients.

Cutis Laxa syndrome: a case report.

Cutis laxa (CL) is a heterogeneous group of inherited and acquired connective tissue disorders characterized by a loose skin and variable systemic involvement (inguinal hernia, cardiopulmonary disease, and emphysema). Autosomal dominant, autosomal recessive and x-linked recessive patterns have been described in the inherited forms. Acquired forms of this disease have been associated with a previous inflammatory skin disorder (urticaria…). The characteristic symptomatological pattern is resulting from paucity of elastic fibers. We report an 18 months old baby boy with a congenital cutis laxa. He was admitted in pediatric unit for respiratory disorders. The diagnosis of CL syndrome is based on clinical assessment of typical skin features and the associated extracutaneous finding.

Multicentric Castleman's Disease in a Child Revealed by Chronic Diarrhea.

Multicentric Castleman's disease is a rare benign and unexplained lymphoproliferative disorder that is extremely uncommon in children. It presents with fever, systemic symptoms, generalized lymphadenopathy, and laboratory markers of inflammation. Its treatment is not standardized and its prognosis is poor. We report a novel case of multicentric Castleman's disease in a 13-year-old girl who had presented with chronic diarrhea as the only initial presenting symptom. The diagnosis of celiac or inflammatory bowel diseases was suspected, but two and a half years later, the diagnosis of multicentric Castleman's disease was brought following the appearance of abdominal mass whose biopsy revealed Castleman's disease in the plasma cell form. The outcome was favorable after treatment by corticosteroid, chemotherapy, and surgery. The occurrence of diarrhea as the initial symptom of multicentric Castleman's disease without lymph node involvement is very rare. This case report underlines the diagnostic difficulties and the long interval between onset and diagnosis when diarrhea occurs first.

Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review.

Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug.

Hodgkin's Lymphoma Revealed by Hemophagocytic Lymphohistiocytosis in a Child.

Hemophagocytic lymphohistiocytosis (HLH) is a severe life-threatening disorder, responsible for extensive phagocytosis of hematopoietic cells and causing a multisystem organ failure. If lymphomas are common causes of HLH, the association with Hodgkin's lymphoma is rarely described in children. We report a case of a 9-year-old boy presenting with HLH as an initial manifestation of Hodgkin's lymphoma. He has been suffering from persistent high fever, asthenia, weight loss, and hepatosplenomegaly with no lymphadenopathy. The diagnosis of HLH secondary to infectious disease was initially worn. The patient received high-dose intravenous immunoglobulin with broad-spectrum antibiotics. However, his state got worse with the onset of dry cough and pleural effusion. Histopathologic examination of pleural fluid showed the presence of Reed-Sternberg cells. The outcome was favorable after treatment by corticosteroid and chemotherapy. Hodgkin's lymphoma revealed by HLH is a source of delayed diagnosis and should be borne in mind in children.

Crohn's disease presenting as vulvar edema in a 15-year-old girl.

BACKGROUND: Vulval involvement is an uncommon extraintestinal manifestation of Crohn's disease, and it is very rare in children. Patients with vulval CD typically present with erythema and edema of the labia majora, which can progresses to extensive ulcer formation. Vulval CD can appear before or after intestinal problems or it may occur simultaneously. OBSERVATION: We present a 15-years-old girl with bilateral labial hypertrophy which revealed a Crohn's disease. The course of her lesion was independent of the intestinal disease and responded significantly to medical treatment including Mesalamine, corticosteroid and local care. CONCLUSIONS: We emphasize that although vulval involvement in childhood is uncommon, Crohn's disease must be considered in the differential diagnosis of nontender, red, edematous lesions of the genital area.