Visceral leishmaniasis as a rare cause of granulomatous hepatitis.

Visceral leishmaniasis (VL) is a potentially fatal infection caused by species of Leishmania. It is characterized by fever, weight loss, anemia, and enlargement of the spleen and liver. Hepatitis due to VL is one of the causes of granulomatous hepatitis rarely described in the literature. It poses a problem of differential diagnosis with other causes, notably infectious and autoimmune. Hence the need for a global clinical, biological, and histological evaluation to orientate this entity, especially in endemic countries like ours. In the present case study, a 2-year 8-month-old boy was diagnosed with VL and treated with meglumine antimoniate; the evolution was marked after 2 months by the persistence of a large liver; laboratory results showed elevated liver functions and anemia. A liver biopsy was performed, and the histological findings confirmed the diagnosis of granulomatous hepatitis.

Phenotype and molecular characterization of Wilson's disease in Morocco.

BACKGROUND AND STUDY AIMS: In Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients. PATIENTS AND METHODS: We collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters. The genotype was characterized in 18 families diagnosed at the University Hospital Center of Marrakesh, by next generation sequencing. RESULTS: The mean annual prevalence in Morocco was 3.88 per 100,000 and the allele frequency was 0.15 %. Among the 226 patients included (121 males and 105 females), 196 were referred for a hepatic or neurological involvement and 30 were asymptomatic. The mean age at diagnosis was 13 ± 5.1 years (range: 5 - 42 years). Consanguinity was found in 63.3 % of patients. The mean duration of illness was 2.8 ± 1.9 years. Kayser-Fleischer rings were found in 131 (67.9 %) of 193 patients. Among the 196 symptomatic patients, 141/159 (88.7 %) had low serum ceruloplasmin (<0.2 g/L) and a high 24-hours urinary copper (>100 µg/day) was found in 173/182 (95.1 %) patients. The initial treatment was D-penicillamine in 207 patients, zinc acetate in five, zinc sulfate in five, and nine patients were not treated; 60/207 (29 %) patients have stopped treatment. A total of 72 patients died; the mortality rate was 31.9 %. Eight different ATP7B variants were identified among the 18 patients studied, of which two were novel (p.Cys1104Arg and p.Gln1277Hisfs*52), and six previously published (p.Gln289Ter, p.Cys305Ter, p.Thr1232Pro, p.Lys1020Arg, p.Glu583ArgfsTer25 and c.51+4A>T). All informative patients were homozygous for the disease-causing mutation. CONCLUSION: In Morocco, a high prevalence due to consanguinity and a high mortality rate due to the difficulty of diagnosis and lack of treatment were observed in WD patients. NGS sequencing identified new ATP7B variants in WD patients from Morocco.

A large-scale study to describe the prevalence, characteristics and management of functional gastrointestinal disorders in African infants.

AIM: To evaluate the pattern, impact on quality of life and management of common functional gastrointestinal disorders (FGIDs) and related signs and symptoms in infants below 1 year of age in Africa. METHODS: Multicentre, cross-sectional, observational study in 10 African countries. At the first paediatric consultation of children with gastrointestinal symptoms, the perception of paediatricians on FGIDs (infant colic, constipation and regurgitation) and gas/bloating, impact on infant quality of life and parental anxiety and patient management practices were evaluated by standardised questionnaires. RESULTS: Questionnaires were completed by 759 paediatricians for 10 812 infants. Overall, 49.9% of paediatricians reported ≥30% of first infant consultations each month for FGIDs or related symptoms. Infant colic was most commonly diagnosed (57.6% of infants), followed by gas/bloating (43.2%), regurgitation (39.7%) and constipation (31.4%). Overall, 53% presented >1 symptom. Mean scores for infant quality of life, sleep and parental anxiety were worse when children had multiple symptoms compared to children with a single symptom (P < .025). Prescription of medication was common (62.4%). There were no consistent differences between countries. CONCLUSION: Functional gastrointestinal disorder occurrence in Africa was high with a gap between expert recommendation that emphasises parental reassurance and nutritional advice and daily practice, particularly prescription of medication.

Review shows that parental reassurance and nutritional advice help to optimise the management of functional gastrointestinal disorders in infants.

AIM: Regurgitation, infantile colic and functional constipation are common functional gastrointestinal disorders (FGIDs) during infancy. Our aim was to carry out a concise review of the literature, evaluate the impact of these common FGIDs on infants and their families, and provide an overview of national and international guidelines and peer-reviewed expert recommendations on their management. METHODS: National and international guidelines and peer-reviewed expert recommendations on the management of regurgitation, infantile colic and functional constipation were examined and summarised. RESULTS: Regurgitation, infantile colic and functional constipation cause frequent parental concerns, lead to heavy personal and economic costs for families and impose a financial burden on public healthcare systems. Guidelines emphasise that the first-line management of these common FGIDs should focus on parental education, reassurance and nutritional advice. Nutritional advice should stress the benefits of continuing breastfeeding, while special infant formulas may be considered for non-breastfed infants with common FGIDs. Drug treatment is seldom required, with the exception of functional constipation. CONCLUSION: By providing complete and updated parental education, reassurance and nutritional advice, healthcare professionals can optimise the management of FGIDs and related symptoms and reduce the inappropriate use of medication or dietary interventions.

Iron for Africa-Report of an Expert Workshop.

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue.

Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: a real life prospective study.

BACKGROUND: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources. METHODS: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities. RESULTS: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD. CONCLUSIONS: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies.

Prevalence and Health Outcomes of Functional Gastrointestinal Symptoms in Infants From Birth to 12 Months of Age.

OBJECTIVES: The aim of the study was to review published evidence and the opinion of practising clinicians on the prevalence and long-term health consequences of functional gastrointestinal symptoms in infants younger than 12 months. METHODS: PubMed was searched from inception to November 2014 to find articles reporting the prevalence and long-term health outcomes of infantile colic, regurgitation, functional constipation, functional diarrhoea, and dyschezia in infants younger than <12 months. A questionnaire was sent to practising clinicians worldwide, and a group of 15 international experts met to discuss the likely frequency and longer-term consequences of these symptoms. RESULTS: The literature search identified 30 studies reporting the prevalence of infantile colic (2%-73%), 13 that of regurgitation (3%-87%), 8 that of functional constipation (0.05%-39.3%), 2 that of functional diarrhoea (2%-4.1%), and 3 that of dyschezia (0.9%-5.6%). The studies varied in design, populations investigated, and definition of the symptoms. Questionnaires were received from 369 respondents. The experts agreed that the likely prevalences for colic, regurgitation, and functional constipation were 20%, 30%, and 15%, respectively. The limited data in the literature for functional diarrhoea and dyschezia suggest prevalences <10%. Infantile colic may be associated with future health problems in a subset of infants. CONCLUSIONS: Functional gastrointestinal symptoms appear to occur in a significant proportion of infants younger than 12 months and may have an impact on future health outcomes. Prospective collection of data according to agreed criteria is needed to obtain more accurate estimates of the prevalence and consequences of these symptoms.

Celiac disease in the Mediterranean area.

BACKGROUND: The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. METHODS: By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. RESULTS: The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. CONCLUSIONS: This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines.

Burden of celiac disease in the Mediterranean area.

AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available confidence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic profiles amongst Mediterranean countries. RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550,000 symptomatic adults and about 240,000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600,000 celiac patients will die in the next 10 years, with an excess of 44.4% vs age- and sex-matched controls. CONCLUSION: In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.

A rare cause of painful cervical swelling: myositis ossificans progressiva in childhood. Report of a case.

Myositis ossificans progressiva (MOP) is a rare condition of which we report a case in a 13-year-old girl with involvement of the cervical paraspinal and periscapular muscles. No ectopic ossifications were visible on plain radiographs. Computed tomography disclosed diffuse inflammation. Plain radiographs of the toes confirmed the diagnosis by visualizing characteristic bone abnormalities. Knowledge of the digital abnormalities seen in MOP is important to avoid unnecessary diagnostic investigations, most notably a surgical biopsy, which may trigger a flare of the disease. The prognosis is guarded.