• Clinical science

Hirschsprung's disease

Abstract

Hirschsprung's disease (congenital aganglionic megacolon) is an inherited disorder primarily affecting newborns. The condition is characterized by an aganglionic colon segment, usually the rectosigmoid region, which fails to relax leading to functional intestinal obstruction. The first sign of the disease is often when a newborn fails to pass meconium within 48 hours after birth and/or shows symptoms of gastrointestinal obstruction (e.g., bilious vomiting and abdominal distention). The onset and severity of symptoms vary according to the length of the aganglionic segment (a longer aganglionic segment is associated with an early and more severe onset). Diagnosis usually involves three different modalities: contrast enema, anorectal manometry, and stepwise biopsy for histological detection of aganglionosis. Treatment of choice is surgical resection of the aganglionic segment, although it is important to maintain anal sphincter function. A severe complication of the disease is Hirschsprung enterocolitis, which presents with abdominal pain, fever, and foul-smelling and/or bloody diarrhea. If not treated promptly, this condition can progress to e.g., toxic megacolon or sepsis. The prognosis for patients with Hirschsprung's disease is good if treated at an early age.

Epidemiology

  • Sex: > (4:1)
  • Associations: trisomy 21 and additional syndromes (e.g., MEN2 and Waardenburg syndrome)
  • Risk factor: family history of Hirschsprung's disease
  • In approximately 80% of cases, Hirschsprung's disease is limited to the rectosigmoid region.

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

Hirschsprung's disease is caused by defective caudal migration of parasympathetic neuroblasts (precursors of ganglion cells) from the neural crest to the distal colon. This process takes place between the 4th and 7th week of development. Affected segments are histologically characterized by the absence of the Meissner plexus and Auerbach plexus (submucosal and myenteric plexus ganglion) beginning at the anorectal line, leading to:

  • Inability of the myenteric plexus to control the intestinal wall muscles → uncoordinated peristalsis and slowed motility
  • Spastic contraction of intestinal muscles → stenosis
  • Expansion of the colon segment proximal to the aganglionic section (possible megacolon)

References:[2][4]

Clinical features

Early presentation

  • Delayed passage of meconium
  • Distal intestinal obstruction: abdominal distention and bilious vomiting
  • Tight anal sphincter with explosive release of stools and air upon removal of the finger
  • Failure to thrive/poor feeding
  • Palpation of feces via the abdominal wall

Late presentation

Less severe Hirschsprung's disease

References:[2][1][4]

Subtypes and variants

Total colonic aganglionosis

  • Definition: complete aganglionosis of the colon
  • Symptoms: ranging from incomplete intestinal obstruction to ileus
  • Prognosis: significant long-term morbidity and mortality (e.g., enterocolitis, post-operative bowel incontinence)

Diagnostics

Imaging is the best initial test, however, a rectal biopsy is the gold standard for confirming the diagnosis. Anorectal manometry may be considered as an additional screening test if the clinical presentation is atypical or the patient is older.

Imaging

Abdominal x-ray

  • Best initial test
  • Findings:
    • Decreased or absent air in rectum
    • Dilated colon segment immediately proximal to aganglionic region
    • Distal intestinal obstruction

Barium enema

  • Indication: Usually performed in addition to x-ray, to localize and determine the length of the aganglionic segment prior to surgery
  • Findings:
    • Change in caliber along the affected intestinal segment
    • Retention of barium for 24–48 hours

Anorectal manometry

  • Measures the relaxation pressure of the internal anal sphincter after distention with a balloon. Difficult to perform in newborns as cooperation is essential.
  • Indication: screening in atypical presentations or in older children
  • Findings:
    • Absent relaxation reflex of the internal sphincter after stretching of the rectum (paradoxical increase in pressure)
    • Typical 'mass contractions': lack of physiological, propulsive waves

Rectal biopsy

In approximately 10% of newborns with Hirschsprung's disease, no dilation or change in caliber is found in the colon contrast enema examination → both imaging and rectal biopsy are necessary!

References:[4][5][2][3][1]

Differential diagnoses

Differential diagnosis of intestinal obstruction in neonates

Hirschsprung's disease Intestinal neuronal dysplasia (IND) Meconium ileus Meconium plug syndrome Congenital hypothyroidism
Findings
  • Delayed passage of meconium
  • Abdominal distention and bilious vomiting
  • Barium enema shows a change in caliber along the affected intestinal segment
  • Rectal biopsy shows absence of ganglion cells (aganglionosis)
  • Colicky pain
  • Diarrhea, constipation (in some cases, bloody discharge)
  • Rectal biopsy shows hyperganglionosis as opposed to aganglionosis in Hirschsprung's disease
  • Delayed passage of meconium
  • Abdominal distention
  • Neonatal screening allows early diagnosis of cystic fibrosis
  • Barium enema shows a “microcolon” and meconium pellets in the terminal ileum
  • May have associated cystic fibrosis
  • Constipation
  • Increased birth weight and length may be present (due to myxedema)
  • Neonatal screening allows early diagnosis of this condition

References:[6][7][8]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Surgical treatment is usually performed in two stages:
    • First stage: diverting colostomy to relieve the dilated bowel .
    • Second stage:
      • Resection of the aganglionic segment
      • Anastomoses of the normal ganglionic colon segment to either the distal modified rectum or normal (unmodified) distal rectum.
      • Preservation of internal anal sphincter function is of the utmost importance.

References:[2][3][4]

Complications

References:[2][1][9]

We list the most important complications. The selection is not exhaustive.

Prognosis

  • Good prognosis with early treatment
  • Without treatment, aganglionic megacolon has a mortality rate as high as 80%.

References:[2][10]