FERMENTATIVE DIARRHOEA (DISAccHARIDE INTOLERANcE)

In the healthy child, the disaccharide sucrose is split into the monosaccharides, glucose and fructose by small intestinal sucrase-isomaltase enzyme and the disaccharide lactose into the monosaccharides glucose and galactose by the enzyme lactase. Failure of any of these enzyme systems will result of an excess of disaccharide in the intestine where bacteria will ferment the sugars to produce acid and an increased osmotic bowel content. This results in fermentative diarrhoea with the passage of highly acid watery stools. Symptoms are relieved when the offending disaccharide is removed from the diet. Lactase deficiency inherited as an autosomal recessive disorder causes persistent diarrhoea from birth because both human and cows’ milk contains lactose. When there is a delay in the onset of symptoms this suggests a sucrase-isomaltase deficiency, as sucrose and starch are not usually added to the diet in the first week after birth. In addition to the autosomal recessive inheritance of the deficiency, there can be transient disaccharide intolerance acquired secondarily to gastroenteritis or other intestinal mucosal insult. Investigations, which help to confirm disaccharide intolerance, include the pH of the fresh stool less than 5.5 and the presence of reducing sugars revealed by the Clinitest and by the identification of faecal sugars on thin-layer chromatography. Removal of all disaccharide from the diet and replacement with monosaccharide will result in a resolution of the diarrhoea. Reintroduction of the disaccharide will result in the return of the diarrhoea and there will be a failure of the normal increase in blood glucose of at least 2.8 mmol/L (50 mg per 100 ml) expected in the normal subject. Rarely a monosaccharide malabsorption syndrome (glucose-galactose malabsorption) can occur. Jejunal biopsy will allow direct measurement of enzyme activity in the jejunal mucosa. The diarrhoea in infants with the hereditary forms of the disorder can be abolished by total exclusion from the diet of the offending carbohydrate. Systemic Illness

In addition to the acute diarrhoea caused by food poisoning from food toxins or bacterial toxins, viral, bacterial and protozoal bowel infections there are a number of systemic illnesses, which are complicated by acute diarrhoea and vomiting. Septicaemia, meningitis, pneumonia and infectious hepatitis may be accompanied by diarrhoea and vomiting. Abdominal distension with bloody diarrhoea may suggest an acute surgical condition or the haemolytic uraemic syndrome. Hospital admission is indicated if significant dehydration (more than 5%) is present, when there is doubt about the diagnosis, when hypernatraemia is suspected, when an

underlying medical condition such as adrenogenital syndrome or chronic renal insufficiency is present or when outpatient management has failed or is thought to be inappropriate due to adverse social or other circumstances.

PARASITIc INTESTINAL INFEcTION

It is estimated that between 800 million and 1,000 million people in the world are suffering from at least one type of worm infection. The most important intestinal worms are nematodes and cestodes.

NEMATODES

These are round, elongated, non-segmented worms with differentiation of the sexes.

Roundworm (Ascaris Lumbricoides) Mode of Infection

Infection arises from swallowing ova from soil contaminated with human excreta. The ova are not embryonated when passed in the faeces but they become infective in soil or water. When swallowed by man the hatched larvae penetrate the intestinal wall and pass via the liver and lungs to the trachea, oesophagus, stomach and intestine where they grow into mature worms (Fig. 7.5).

Clinical Effects

A few roundworms in a well-fed patient usually produce no ill effects and are not noticed until a worm is either vomited

or passed in the stool. Typical clinical features include: a protuberant abdomen, intermittent intestinal colic, digestive disturbance, general debility, loss of appetite and insomnia. In heavy infections, worms may migrate into and block the bile duct producing jaundice while similar blocking of the appendix can cause appendicitis. In very heavy infections, intestinal obstruction can occur from a tangled ball of roundworms. The presence and extent of roundworm infection is readily detected by microscopical examination of the stools for ova.

Piperazine citrate in a single oral dose of 75 mg/kg to a maximum single dose of 5 g will clear roundworm from 75% of patients. Two doses on successive days give a marginally higher cure rate. Piperazine citrate has minimum adverse effects—very occasionally unsteadiness and vertigo. Mebendazole is active against threadworm, whipworm and as well as roundworm infections and can be safely recommended for children over the age of 2 years. A dose of 100 mg twice daily for 3 days is effective. Mebendazole is generally considered to be the drug of choice. Levamisole is an alternative when mebendazole cannot be used.

Hookworms (Ankylostoma duodenale and Necator Americanus)

There are two types of hookworms: (1) Ankylostoma duodenale being most commonly found in Egypt, Africa, India and Queensland, and also in the Southern USA and (2) Necator americanus, which is found in the Americas, the Philippines and India. These two species differ in small anatomical details but their life cycles are identical (Fig. 7.6). The male and

female worms live chiefly in the jejunum. The worm attaches itself to the intestinal mucosa by its teeth and sucks blood. The ova, passed in the faeces, hatch out in water or damp soil and larvae penetrate the skin of the buttocks or feet. They reach the heart and lungs by the lymph vessels and bloodstream, penetrate into the bronchi, are coughed up into the trachea and then pass down the oesophagus to mature in the small intestine. Clinical Effects

The main clinical picture of disease is caused by prolonged loss of blood. Therefore the clinical manifestations of infection depend on the number of worms present and the nutritional state of the patient. A few hookworms in a fairly well-fed person produce no disease as the small blood loss is constantly being replaced. In children whose diet is inadequate and the worm load heavy, severe anaemia may stunt growth, retard mental development and in very severe cases, result in death through heart failure. Infection is diagnosed by microscopical examination of the stools for eggs, the number of which indicates the severity of infection (72,000 ova/g = significant infection).

Treatment

Children with severe anaemia and malnutrition should have blood transfusion and nutritional support before definitive worm therapy is started. Mebendazole has a useful broad- spectrum activity and is effective against hookworms; the usual dose for children over one year of age is 100 mg twice daily for 3 days. Albendazole given as a single dose of 400 mg in children over 2 years is an alternative. Levamisole is also effective.

Strongyloidiasis (Strongyloides Stercoralis) These worms are fairly widespread in warmer climates and may be found concurrently with hookworm infection.

Incidence is often highest in children and the usual mode of infection is penetration of the skin by infective larvae present in the soil. Migration through the lungs also occurs and can produce respiratory signs and there may be abdominal distension, bloody diarrhoea and anaemia. Creeping eruptions, particularly around the buttocks, can develop as a result of the reinfection. Diagnosis is made by identification of larvae in the faeces.

Invermectin given to children over the age of 5 years in a dose of 200 mg/kg daily for 2 days may be the most effective drug for chronic Strongyloides infection. Albendazole is an alternative with fewer side-effects; it is given to children over 2 years of age in a dose of 400 mg once or twice daily for 3 days, repeated after 3 weeks if necessary.

Threadworm (Enterobius Vermicularis, Oxyuriasis, Pinworm or Seatworm)

The male worm is about 3 mm in length and the female, which looks like a small piece of thread, is about 10 mm. The female lives in the colon. Eggs are deposited on the perianal skin by the female contaminating the fingers of the child who may then reinfect himself. The ova after ingestion hatch in the small intestine. The male worm also fertilises the female in the small intestine, after which the male dies while the female migrates to the caecum. It is common for this infestation to affect all members of a family because the ova can be found on many household objects. The initial infection may also be acquired from contaminated water or uncooked foodstuffs (Fig. 7.7).

Clinical features of enterobiasis are mainly perianal, perineal and vulval pruritus, which can interfere with sleep. Scratching leads to secondarily infected dermatitis and to reinfection through contaminated fingers. Heavy infestations could be associated with episodes of severe abdominal

Fig. 7.7: The life cycle of the threadworm Fig. 7.6: The life cycle of the hookworm

pain. The association of appendicitis with threadworms is exceptionally rare. Diagnosis is made by direct examination of the worms or ova trapped by “sellotape” applied sticky side to the anal skin early in the morning and then stuck on to a glass slide.

Mebendazole is the drug of choice for treating threadworm infection in children over 6 months. It is given as a single dose as reinfection is very common, a second dose may be given after 2 weeks. Piperazine is also effective. Measures to break the cycle of reinfection should be taken and these include scrupulous personal hygiene, boiling all infected linen and the wearing of occlusive clothing to prevent scratching. Treatment should also be given to other members of the family and it should be reinstituted when symptoms recur and eggs are again found in the perineal area.

Larva Migrans

Cutaneous Variety (Creeping Eruption)

Cutaneous larva migrans is caused by the infective larvae of various dog and cat hookworms. These larvae can penetrate the human skin and finding themselves in an unsuitable habitat wander around in the epidermis for several weeks. Their progress is marked by a characteristic itching and a serpiginous urticarial track. The infection is more common in children than in adults and is occasionally seen in people recently returned from tropical countries.

Treatment by freezing the advancing end of the track with dry ice or liquid nitrogen is no longer recommended. Applications of topical 15% thiabendazole powder in water soluble base with or without diethylcarbamazine 5 mg/kg per day for 7 days will eliminate the larvae. Multiple infections respond to invermectin, albendazole or thiabendazole by mouth.

Visceral Variety

This is caused by various species of the nematode Toxocara, usually Toxocara canis the common roundworm of the dog. The larvae may penetrate the intestinal wall but are unable to migrate to the lungs of their unnatural host and pass through or become encysted in liver, lungs, kidneys, heart, muscle, brain or eye, causing an intense local tissue reaction. The child may fail to thrive, develop anaemia and become pyrexial with a cough, wheeze and hepatosplenomegaly. There is usually a marked eosinophilia and there can be CNS involvement. In addition to this generalised form of the disorder, there may in the older child (7–9 years old), isolated loss of sight in one eye associated with ocular toxocariasis. The diagnosis can only be established with certainty from a tissue biopsy; generally taken from the liver and the Toxocara ELISA test is a useful screen.

Recently thiabendazole 50 mg/kg body weight for 3–5 days has been shown to kill encysted larvae and is especially useful for early ocular lesions. Normally the visceral variety is self-limiting and requires no treatment. Regular and routine deworming of puppies and pregnant bitches with mebendazole, prevention of face licking by dogs and the need to wash hands carefully after handling pets are preventative health measures. Multiple infections respond to invermectin, albendazole or thiabendazole by mouth.

cESTODES

Cestodes (tapeworms) of importance to humans are Taenia saginata (beef tapeworm), T. solium (pork tapeworm), Hymenolepis species (dwarf tapeworm), and T. echinococcus (hydatid cyst).

The ingestion of raw or inadequately cooked beef or pork can result in human infection. Man is the definitive host for both the beef (T. saginata) and pork (T. solium) tapeworms. Although the infections may be asymptomatic, epigastric discomfort, increased appetite, dizziness and loss of weight sometimes occur. These features may be more marked in children and debilitated persons. Diagnosis is based on the passage of gravid segments through the anus. The differentiation can be made by a microscopical study of the number of lateral branches in the gravid uterus of each segment, the uterus of T. solium having about 10 branches and that of T. saginata about 20.

With T. solium infection a major danger is the ingestion of eggs from an infected person (heteroinfection) or self- ingestion of eggs (autoinfection). This can give rise to cysticercosis where cysticerci develop almost anywhere including brain, skin, muscle and eye.

Taenia Echinococcus (Hydatid cyst)

The definitive host of T. echinococcus is the dog, wolf, fox or jackal. Man and sheep may become the intermediate host by swallowing the ova from the dog and this is especially likely in sheep-rearing countries. The adult worm in the dog is very small (0.5 cm) but the ingested ovum when swallowed by man liberates a 6-hooked oncosphere into the small intestine. This penetrates to the tissues, usually the liver but sometimes lung, bones, kidneys or brain to form a hydatid cyst. This has a 3-layered wall—an outer layer of host fibrous tissue, a laminated middle layer and an inner germinal layer that produces many daughter and granddaughter cysts.

Clinical Effects

These are largely due to local pressure effects. The liver may be greatly enlarged and there may be a palpable rounded swelling over which the classical “hydatid thrill”

can be elicited. Ultrasound and CT scanning can reveal the cystic nature of the lesions. Eosinophilia may be marked. The diagnosis may be confirmed by complement fixation, haemagglutination or latex-slide agglutination tests but the hydatid ELISA test and improved immunoelectrophoresis tests are likely to prove more specific.

Treatment

The only measure is surgical incision. The cyst must never be tapped as a leakage of hydatid fluid into the tissues can cause shock or death. The outlook is grave if suppuration occurs within the cyst. Spontaneous recovery can occur if the cyst dies, inspissates and calcifies. Medical treatment for this most important tapeworm infecting man is generally unsatisfactory but albendazole is used in conjunction with surgery to reduce the risk of recurrence or as primary treatment in inoperable cases. Albendazole is given to children over 2 years of age in a dose of 7.5 mg/kg (maximum 400 mg) twice daily for 28 days followed by 14-day break and then repeated for up to 2–3 cycles. Careful monitoring of liver function is particularly important during drug treatment.

Hymenolepis (Dwarf Tapeworm)

Mild infestations due to Hymenolepis (dwarf tapeworm) cause no symptoms, but heavy infestations can sometimes cause diarrhoea, irritability and fits. Diagnosis is made by finding the typical ova in the faeces.

Treatment

Niclosamide is the most widely used drug for tapeworm infections and side effects are limited to occasional GI upset, light-headedness and pruritus. It is not effective against larval forms. A laxative may be given 2 hours after the dose; an antiemetic may be given before treatment.

Praziquantel is as effective as niclosamide and is given to children over 4 years of age as a single dose of 10–20 mg/kg after a light breakfast (or as a single dose of 25 mg/kg for Hymenolepis nana).

INFLAMMATORy BOWEL DISEASE

The term inflammatory bowel disease (IBD) includes two clinical conditions in children, ulcerative colitis and Crohn disease (Table 7.2). On the whole the prognosis of chronic IBD in childhood is good.

ulcerative colitis Aetiology

The aetiology is unknown. It is fortunately rare in children. Over the past decade, it would appear that there has been

little change in the incidence of ulcerative colitis but Crohn disease has increased. The reason for the change is not clear.

Severe behavioural problems in some of the affected children and their families have sometimes led physicians to regard the disease as a psychosomatic disorder, but the evidence in support of this hypothesis is extremely slender. Food allergy has been suspected, but only a small group of patients respond to withdrawal of milk. Boys and girls are equally affected. The mean age of onset is about 10 years. There is no clear-cut inheritance pattern but ulcerative colitis is more common in first-degree relatives than in the general population.

Pathology

The mucous membrane of part or all of the colon and sometimes of the terminal ileum becomes hyperaemic, oedematous and ulcerated. The lesion is continuous rather than patchy and usually involves only the mucosal and submucosal layers. The earliest lesion in many cases is a crypt abscess (Fig. 7.8). Granuloma formation is rare. In some cases, oedema may give rise to pseudopolypoid nodules. Ulceration may extend through the muscularis and perforation of the colon can occur. Usually perforation is preceded by toxic megacolon with dilatation of an ulcerated segment of the large bowel. Carcinoma is a common late complication. Hepatic complications such as sclerosing cholangitis and chronic active hepatitis can occur with ulcerative colitis in childhood.

Table 7.2: Clinical features of ulcerative colitis and Crohn disease

Clinical features Ulcerative colitis Crohn

disease

Location Rectum and colon (variable)

Ileum and right colon

Diarrhoea Severe Moderate Mucus blood Frequent Infrequent Rectal involvement Always Infrequent Fistula in ano Absent Infrequent Perirectal abscess Absent Infrequent Abdominal wall

fistula Absent Infrequent

Toxic megacolon Infrequent Absent

Arthritis Rare Common

Eye pathology Rare Iridocyclitis, granuloma Proctoscopic

appearance

Diffuse, ulceration Cobblestone

Small bowel involvement

Absent Frequent Microscopic

appearance

Mucosal ulceration Transmural granulomas

Clinical Features

The onset is sudden with diarrhoea and the frequent passage of small stools containing blood and mucus. This tends to be most severe during the early morning but may also be nocturnal. There may be abdominal pain, anorexia, weight loss or poor weight gain. Tenesmus is common.

Hypochromic anaemia due to chronic blood loss is almost invariably present. Hypoproteinaemic oedema may develop. Associated extraintestinal manifestations of the disease are more common in children than in adults. They may include erythema nodosum, aphthous stomatitis, conjunctivitis, iridocyclitis, haemolytic anaemia, arthralgia or arthritis, pyoderma gangrenosum and finger-clubbing.

After exclusion of infective causes of bloody diarrhoea the diagnosis should be confirmed by rectosigmoidoscopy, mucosal biopsy and barium enema. The last shows loss of normal haustrations in the colon and the so-called “lead- pipe” appearance (Fig. 7.9). Colonoscopy may allow the examination of the whole colonic mucosa and thus the extent of the disease. Radiologically differentiation of Crohn disease from ulcerative colitis can be made on the basis that Crohn disease can affect any part of the GI tract and is patchy in distribution, whereas ulcerative colitis is a continuous lesion affecting only the rectum, colon and occasionally the terminal ileum (backwash ileitis). It is worth remembering that early in the course of disease no X-ray abnormality may be found.

Ulcerative colitis frequently runs an acute course in the child. The cumulative risk of carcinoma of the colon is 20% per decade after the first decade of the illness. Dysplastic changes in the colonic epithelium are considered to be premalignant.

crohn Disease Aetiology

This disorder like ulcerative colitis is not common in children