Hirschsprung's disease

Synonyms: congenital aganglionosis, congenital megacolon, megacolon congenitum

Description¹

• The underlying pathology is an absence of parasympathetic ganglion cells in the myenteric and submucosal plexus of the rectum, possibly extending to the colon.

• Ganglion cells are derived from the neural crest and migrate caudally with the vagal nerve fibres along the intestine. They arrive in the proximal colon by 8 weeks of gestation and in the rectum by 12 weeks.

• Arrest in migration leads to an aganglionic segment which is unable to relax, leading to a functional colonic obstruction.

• The result is clinical Hirschsprung's disease.

• The small intestine may also (very rarely) be involved.

How common is Hirschsprung's disease? (Epidemiology)

• Affects 1 in 5,000 live births worldwide.²

• A study in the North of England found a live birth prevalence of 1.65 per 10,000 live births.³

• The male to female ratio is 4:1.¹

• At least half of all cases are diagnosed in the first year of life and, by the age of 2, most have been diagnosed.

• There are a few in whom diagnosis is delayed until later childhood or even adulthood.

Genetics

• Online Mendelian Inheritance in Man (OMIM) lists a number of different gene sites for Hirschsprung's disease:
  

  • One is on the X chromosome and could help to explain the male preponderance.⁴

  • Another variation called Hirschsprung 2 is on chromosome 13.⁵

  • Hirschsprung modifier 1 is on chromosome 10.

  • There is short-segment disease due to problems on chromosome 3 and 19.^{6 7}

• There are many other variants also listed in OMIM.

Associated diseases

• There may be an association with multiple endocrine neoplasia of the MEN2A and MEN2B varieties.⁸

• One study found that 15% of patients with Hirschsprung's disease also had Down's syndrome.⁹

• Other associations include Waardenburg's syndrome, congenital deafness, malrotation, gastric diverticulum, and intestinal atresia.¹⁰

• Meconium plug syndrome is an association in 3-38% of cases.¹¹

Hirschsprung's disease symptoms¹

History

Neonatal period

• Abdominal distention, failure of passage of meconium within the first 48 hours of life and repeated vomiting.

• Delayed passage of meconium is very important, as nearly half of all infants with Hirschsprung's disease do not pass meconium within 36 hours and nearly half of infants with delayed first passage of meconium have Hirschsprung's disease.

Older infants and children

• These present with chronic constipation that is resistant to the usual treatments and a daily enema may be required.

• Rarely, they have soiling and overflow incontinence.

• This is in contrast to children with functional constipation.

• The disease causes early satiety, abdominal discomfort and distension due to the constipation and this leads to poor nutrition and poor weight gain.

Enterocolitis

• This can develop at any age.

• There is typically abdominal pain, fever, and foul-smelling and possibly bloody diarrhoea, with vomiting.

• If not recognised early, this may progress to sepsis, transmural intestinal necrosis and perforation.

• The mortality with this condition is around 30-35% and this accounts for most of the mortality associated with Hirschsprung's disease.

• Hirschsprung patients who develop enterocolitis have a different mix of enteral organisms than those who do not.¹²

Examination

Neonatal period

• They may have abdominal distention (which is tympanic on percussion) and symptoms of intestinal obstruction.

• They may present with acute enterocolitis in this age group and (rarely) with neonatal meconium plug syndrome or appendicitis.

A quarter of infants with Hirschsprung's disease pass meconium within 24 hours of birth and nearly half within 48 hours of birth, limiting the validity of timing of first meconium as a screening question for Hirschsprung's disease.¹³ In addition, one in three infants with Hirschsprung's disease are discharged home after birth, prior to diagnosis, placing a heavy burden on primary care to ensure timely referral.

Older infants and children

• They have chronic constipation.

• There may be marked abdominal distention with palpable dilated loops of colon.

• Rectal examination often reveals an empty rectum and may result in the forceful expulsion of faecal material as examination is completed.

• More rarely, older children can present with malnourishment and possibly enterocolitis.

Differential diagnosis

In the neonatal period the main alternative diagnosis with delayed passage of meconium is meconium ileus which suggests cystic fibrosis. In older patients, other causes of chronic constipation and intestinal obstruction should be considered.

Investigations

• Raised white blood cell count - possibility of enterocolitis.

• Imaging - plain abdominal X-ray may show obstruction (usually a dilated lower bowel).¹⁴ Contrast imaging may be normal in the first three months of life and in patients with total colon involvement. Double-contrast barium enema may show a markedly dilated proximal colonic segment with a transition zone and a narrowed distal colonic segment. Similar findings may be demonstrated by CT scanning. These appearances in an adult with chronic constipation should suggest a diagnosis of Hirschsprung's disease.¹⁵

• Anorectal manometry - in older children with chronic constipation and an atypical history for either Hirschsprung's disease or functional constipation, anorectal manometry can be helpful in making or excluding the diagnosis. In Hirschsprung's disease there is failure of reflex relaxation of the internal anal sphincter in response to inflation of a rectal balloon. One study found that anorectal manometry was a more accurate diagnostic tool than barium enema.¹⁶ It should not, however, replace rectal suction biopsy.¹⁷

• Rectal biopsy - the definitive diagnosis rests on histology of a rectal biopsy. Tissue is obtained either by suction anal biopsy or by transanal wedge resection. Suction biopsy is best performed 2-2.5 cm above the dentate line, on the posterior wall to reduce the risk of perforation. The specimen is examined for the presence or absence of ganglion cells in the myenteric plexus. This may be difficult in short segments or with skip lesions and acetylcholine staining may be helpful.¹⁸

• Detection of serum proteins - the detection of serum proteins to aid early screening and diagnosis of Hirschsprung's disease looks promising.¹⁹

Hirschsprung's disease treatment and management

Acute problems

• Presence of intestinal obstruction - intravenous rehydration, gastric and intestinal decompression and cessation of oral feeding are required. Decompression may be achieved by a nasogastric tube from above and digital rectal examination or normal saline enemas once or twice a day from below.²⁰

• Presence of enterocolitis - requires broad-spectrum antibiotics and aggressive intravenous rehydration.²¹

Surgical options

• The surgical options are limited by the patient's age, mental status, ability to perform activities of daily living, length of the aganglionic segment, degree of colonic dilation, and any enterocolitis.

• Swenson's procedure was the original procedure performed for Hirschsprung's disease. It involves releasing the defective distal colon to just above the anal canal and performing an end-to-end anastomosis. Thus, the aganglionic segment is removed.

• More recently, a transanal approach has been used. A full-thickness incision is made on the rectal wall posteriorly, 0.5 cm above the dentate line. The mobilised segment is resected about 5 cm above the transition zone. Frozen sections are performed whenever the transition zone is not clearly seen intra-operatively. The operation is completed by full thickness colo-anal anastomosis.²²

• Various modifications concerning the length of the dissected rectum and the shape and length of the anastamosis continue to be developed.²³

No special diet is required in patients with Hirschsprung's disease (unless they have acute obstruction or enterocolitis) and correction of the defect usually results in a normally functioning gastrointestinal tract.

Future therapy

There is some hope that the use of autologous neural crest-derived enteric stem cells or tissue engineering may be a treatment for Hirschsprung's disease. This would mean avoidance of surgery which has the risks of faecal incontinence. ²

Complications¹

Complications can include:

• Soiling and incontinence (<1%).

• Persisting constipation (~ 10%).

• Leakage of the anastomosis.

• Enterocolitis - one study reported an incidence of 12%.

• Stricture of the resected segment - a late complication.

• Late intestinal obstruction - possibly due to adhesions.

Prognosis

• After resection 30-50% of patients may continue to experience symptoms.²

• Most children acquire faecal continence and normal bowel habits but a number of older children still have ongoing continence problems.²⁴ Unsurprisingly, acquirement of faecal continence is associated with an improvement in quality of life.

• The prognosis with Down's syndrome is less favourable and some people recommend permanent colostomy.

History

• The first report of a patient with Hirschsprung's disease was made in 1691 by Frederik Ruysch. He was a Dutch anatomist and botanist who lived from 1638 to 1731. He studied medicine in Leiden and was awarded MD in 1664. He had a passion for anatomy and would ask grave diggers to open graves so that he could study the corpses.

• Harald Hirschsprung was a Danish paediatrician who was born in 1830 and died in 1916. His father founded a tobacco factory but he refused to join the business. He published the classical description of congenital megacolon in 1886.