It is a great pleasure to introduce this special issue on gastroenterology. We are very grateful to all the contributors who kindly put so much effort into their contributions, and also to Stephen Allen, Olusegun Akinyinka and Akinlolu Adepojou for writing the editorial.
Upper gastrointestinal (UG) disorders are common in children. Owing to a lack of awareness combined with limited diagnostic facilities, they are often under-reported in low- and middle-income countries (LMIC).
Ujjal Poddar has written a detailed review of three common UG disorders relevant to both LMIC and high-income countries (HIC): gastro-oesophageal reflux disease (GERD), Helicobacter pylori and upper gastro-intestinal bleeding.
Up to half of healthy infants regurgitate at least once a day which peaks at 4 months and subsides in 90% by 12 months. Continuation or appearance of regurgitation after 18 months should prompt consideration of a pathological cause. The prevalence of gastro-oesophageal reflux (GER) in infants is similar in HIC and LMIC. Parental education and support is an essential part of management.
GERD refers to a range of symptoms and complications owing to pathological GER. The prevalence of GERD increases with age and there can be severe, even life-threatening complications. GERD symptom questionnaires, e.g. the Orenstein infant GER questionnaire (i-GERD), are useful in differentiating between GER and GERD. Investigations are tailored to the type and severity of symptoms.
Proton pump inhibitors (PPI) are more effective than histamine 2 receptor antagonists in the management of GERD. Nissen fundoplication is an option when medical therapy has failed. It is most often required in neurologically impaired children in whom, unfortunately, it is least likely to be effective.
H. pylori is associated with chronic active gastritis (usually asymptomatic), peptic ulcer and gastric cancer. In LMIC, it is often acquired in early childhood and the prevalence may be up to 60–80% owing to poor socio-economic status, over-crowding and poor sanitation and hygiene. It is transmitted by faecal/oral, gastric/oral and oral/oral routes. Its prevalence in HIC is 1–12%. The relationship between H. pylori infection and gastro-intestinal symptoms in children is unclear; there is no evidence that it is a cause of recurrent abdominal pain. The ability of H. pylori to cause gastro-intestinal disease relates particularly to virulence factors.
If H. pylori is detected following investigation of gastro-duodenal disease, it should be treated, and eradication of the organism should be confirmed using non-invasive tests, such as the Urea (13-C) breath test or a monoclonal H. pylori antigen test in stool. In children, a ‘test and treat’ strategy is not recommended. Treatment comprises a PPI and two antibiotics.
In LMIC, upper gastro-intestinal (UGI) bleeding is commonly owing to extra-hepatic portal venous obstruction. In HIC, peptic ulcers are commonly the cause, especially in adolescents in whom exposure to non-steroidal anti-inflammatory drugs is an important cause.
In paediatric intensive care units, UGI haemorrhage is frequently caused by stress ulcers or erosions in the stomach or duodenum. As erosions commonly heal within 48 h, they are more likely to be detected by early UGI endoscopy.
The episode of clinically significant bleeding is associated with two or more of the following: respiratory failure, coagulopathy and a paediatric risk of mortality score (PRISM) of more than 10. Blood transfusion is essential for ongoing bleeding but over-transfusion may lead to increased portal pressure with a risk of re-bleeding.
Depending on the cause and severity of bleeding, a variety of disciplines and treatments are required. Intravenous octreotide should be commenced for suspected variceal bleeding and PPI for non-variceal bleeding.
Jeremy Glissen Brown and Prashant Singh’s comprehensive review of coeliac disease (CD) addresses the epidemiology, associated diseases, diagnosis and management. CD is a global disease with an increasing prevalence but it is under-diagnosed owing to inadequate recognition of atypical symptoms and associated disorders, and also, especially in LMIC, a lack of essential skills, equipment and availability of diagnostic markers.
Prevalence studies are based on serological tests and biopsy-based results, the latter yielding fewer positives. A pooled prevalence of CD found it to be lowest in South America (0.4%) and highest in Europe (0.8%) and Oceania (0.8%). In Asia, the majority of biopsy-proven CD studies have been reported from India (0.1–0.6%). The sero-prevalence is 1.2% in the northern region, 0.9% in the north-eastern region and 0.1% in the southern region of India. In the Middle East, biopsy-proven CD prevalences are 0.1–0.6% in Iran, 0.6–0.9% in Turkey and 0.6–0.7% in Israel. African data on biopsy-proven CD are available only for Tunisia (0.14–0.24%), Egypt (1.0%) and Libya (0.7%). In South America, biopsy-proven CD ranges from 1.26% in Argentina to 0.24–0.35% in Brazil. Some seroprevalence data have been obtained from healthy blood donors but these are not true population-based studies.
Many extra-intestinal manifestations are associated with CD and include haematological, hepatic, endocrine and auto-immune disorders. The following serological tests for CD have the highest sensitivity and specificity, respectively: IgA anti-tTG antibodies >95%, >95%; IgA anti-endomysial antibodies (EMA) >90%, 98%; and IgG diaminated gliadin peptides (DGP) >90%, >90%; HLA DQ2/DQ8 has a sensitivity of 91% but a specificity of only 54%.
The European Society of Paediatric Gastroenterology, Haematology and Nutrition (ESPGHAN) has suggested that a diagnosis of CD could be made without biopsy in symptomatic patients who have anti-tTG-antibody titres which are ten or more times the upper limit of normal and who are HLA DQ2/DQ8 and EMA-positive on a second serological sample.
A gluten-free diet (GFD) requires strict avoidance of wheat, rye and barley and their carrier proteins (gluten, secalin and hoerdin, respectively). The disadvantage of oats which are generally tolerated in CD is that, particularly in LMIC, they may be contaminated by gluten during harvesting and milling, for example.
Major restrictions for families with CD in LMIC include poor counselling regarding diet and management, inadequate labelling of gluten-free foods and the availability and cost of gluten-free products.
Wiparat Manuyakorn and Pornthep Tanpowpong’s wide-ranging review of cow milk protein and other common food allergies and intolerances includes the aetiology (if known), age of onset and resolution, presentation, diagnosis, management and prevention.
Adverse reactions to food are reported in 6.25–28% of children and are classified as food allergy and food intolerance. Food allergy is an immunological reaction and can affect various organs. Food intolerance is a non-immunological reaction which includes metabolic, toxic, pharmacological and undefined mechanisms.
Food allergy results from the breakdown of immunological and clinical tolerance of an ingested food. There are three major groups: (i) IgE-mediated food allergy; (ii) non-IgE-mediated food allergy (of which there are five subgroups); and (iii) mixed IgE and non-IgE-mediated food allergy. The prevalence of food allergy ranges from 1% to 10%, varying between countries and regions, and is increasing worldwide. Cow milk allergy is the most common in children, followed by hen egg.
Food intolerance is often confused with food allergy and it can overlap with a variety of disorders, such as irritable bowel syndrome. There is no simple confirmatory test. Investigation includes double-blind, placebo-controlled food challenges but these are rarely undertaken in children. Examples of food intolerance include lactose, non-coeliac gluten sensitivity (gluten sensitivity in the absence of coeliac disease, viz: positive coeliac serology and/or small bowel histopathological features) and reaction to food chemicals and additives, e.g. histamine, caffeine, sulphites, benzoates and monosodium glutamate.
Food allergy that develops during infancy usually resolves during childhood but food intolerance usually persists into adult life.
Robert Bandsma, Kamran Sadiq and Zulfiqar Bhutta have written an update on the epidemiology, pathogenesis and management of persistent diarrhoea (PD). Of all diarrhoeal episodes in children under 5 years of age in LMIC, approximately 3–20% are considered to last more than 14 days and are therefore defined as persistent diarrhoea.
The pathogenesis of PD is multi-factorial and not fully understood. Factors include inflammation associated with a wide variety of infective agents including bacterial, viral (e.g. HIV) and parasitic organisms.
At present, no microbes are considered to be specific to PD, except possibly enteropathogenic Escherichia coli. Wasting is associated with villous blunting and epithelial barrier dysfunction (malnutrition enteropathy). Environmental enteric dysfunction (EED) is a linear growth faltering condition in young children associated with villous blunting, small intestine inflammation and epithelial barrier impairment and may be partly related to chronic gut infection. Malnutrition enteropathy and EED can be associated with PD. Intestinal inflammatory markers may be elevated in patients with EED and malnutrition enteropathy, and systemic pro-inflammatory cytokine profiles in the latter are similar to those detected in inflammatory bowel disease.
The management of PD has four prongs: hydration, nutritional rehabilitation, antibiotics in certain cases and secondary prevention and supportive therapy. Where possible, patients should be hydrated orally and intravenous (IV) therapy reserved for those in shock. For the latter, especially in severely malnourished children, randomised trials on the rate and type of IV fluids are required. Nutritional rehabilitation is generally undertaken along standard lines for severe malnutrition; the presence of lactose or other food intolerance may require adjustment of the diet. The role of pre- and probiotics and especially of nutrients which can modify the microbiome and restore gut health needs to be explored.
Kapula Chifunda and Paul Kelly describe important parasites associated with the gut, particularly their clinical manifestations and management. Giardia intestinalis (syn. G. lamblia) was the first parasite to be recognised under the microscope by van Leeumenhoek (in his own stool sample) in 1681. The trophozoite adheres to the enterocyte brush border which may be responsible for a mild enteropathy. Although patients with hypogammaglobulinaemia (including IgA deficiency) are at increased risk of chronic giardiasis, those with HIV infection are not and neither are children with Entamoeba histolytica infection. E. histolytica causes amoebic dysentery and amoebic abscess; however, it has to be differentiated from the non-pathogenic E. dispar which is identical microscopically and can only be distinguished from E. histolytica by molecular techniques. Cryptosporidium is responsible for outbreaks of diarrhoea and patients with HIV infection are vulnerable to severe disease. It is associated with growth failure, malnutrition and neurocognitive impairment. Soil-transmitted helminths are generally light, asymptomatic infections. Severe complications occur in Ascaris lumbricoides (obstruction of the gut, biliary or pancreatic ducts), hookworms (anaemia) and Trichuris trichuria (dysentery). One of the main strategies for preventing soil-transmitted helminths has been mass de-worming. A recent systematic Cochrane review did not support this practice.
Strongyloides stercoralis can persist in the body for years. Clinical features include larva currens (skin disease), malabsorption and hyperinfection syndrome. Trichinella spiralis is contracted by eating undercooked pork. The small intestine phase (enteric) is associated with vomiting and abdominal pain and is followed by the migratory phase associated with severe local and systemic symptoms including cardiac and neurological disorders.
There are two important tapeworms, Taenia saginata, acquired by eating beef, and T. solium, by eating undercooked pork. The former is benign but the latter causes neurocystocercosis when there is auto-infection.
Hydatid disease is caused by Echinococcus granularis or E. multi-ocularis and the definitive host is the dog or cat. Diagnosis is by ultrasound and serology. Management is by excision, or aspiration followed by injection of sterilising agents. Albendazole and/or praziquantel is given pre- and post-operatively.
Schistosoma haematobium causes urinary tract disease and S. mansoni and S japonicum hepatosplenic schistosomiasis. The main complication of S. mansoni and S japonicum is oesophageal varices and ascites owing to portal hypertension. Hepatocellular dysfunction is uncommon.
Muhammad Eyad Ba’Ath and Anthony Mark Dalzell have written a comprehensive review of paediatric inflammatory bowel disease (PIBD) with particular emphasis on LMIC. It includes the epidemiology, aetiology, clinical features, diagnosis, medical and, particularly, surgical management and psychological support. They describe the prevalence of PIBD in different parts of the world and among different racial groups. The aetiology of PIBD including environmental factors, diet, intestinal microbiome and genetics are discussed. For diagnosis, oesophagogastroduodenoscopy and ileocolonoscopy remain the procedures of choice, followed by imaging. The review concludes with detailed comment on the difficulties of detection, diagnosis and appropriate management of PIBD in LMIC.
Very early-onset inflammatory bowel disease (VEO-IBD) is defined as that occurring in children under 6 years of age and a subset are those who develop symptoms when under 2 years of age. Xu Teng and co-authors present a case series of six infants under 2 years of age who presented with VEO-IBD in Liaoning Province, China. The age range at diagnosis was 1–3 months and the clinical features were compatible with Crohn disease. Interleukin-10 receptor mutations were detected in five patients. Three patients had compound mutations and two of them died of suspected septicaemia. Haematopoietic stem cell transplantation is considered life-saving in severe cases and one infant who was being prepared for it unfortunately died before it could be administered.
Protein-losing enteropathy is a relatively common condition in gastroenterology. Two case reports describe unusual causes.
Asuman Nur Karhan and co-authors report an 8-month-old girl who presented with acute gastroenteritis. The diarrheoa resolved after a few days but there was persistent vomiting and weight loss and 2 weeks later she developed pedal oedema. Serum albumin was 11.7 g/L and rectosigmoidoscopy demonstrated Entamoeba histolytica. She recovered completely following administration of metronidazole. This is considered to be the first report of amoebic colitis presenting with protein-losing enteropathy.
Islam Nour and co-authors report a 4-year-old girl who presented with generalised oedema and an epigastric mass. There was microscopic hypochromic anaemia (Hb 8.9 g/dL), hypo-albuminaemia (albumin 19 g/L) and elevated α1-antitrypsin clearance which supported protein-losing enteropathy. A large gastric trichobezoar (Rapunzel syndrome) was detected by ultrasound and CT scan. The mass was a cast of the stomach and duodenum and was 60 cm long, stretching into the jejunum. Following removal by laparotomy and nutritional rehabilitation, she made a complete recovery.