Hirschsprung disease

Hirschsprung 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 toxic megacolon or sepsis. The prognosis for patients with Hirschsprung disease is good if treated at an early age.

• Incidence: 1 in 5000 live births ^[1]
• Sex: ♂ > ♀ (4:1)

Epidemiological data refers to the US, unless otherwise specified.

• Genetic causes ^[1]
  • RET gene mutations associated with multiple endocrine neoplasia type 2 (MEN2) and familial Hirschsprung disease
  • Endothelin receptor B (EDNRB) gene mutations associated with Waardenburg syndrome
• Associated conditions ^[1][2]
  • Trisomy 21
  • Multiple endocrine neoplasia type 2 (MEN2)
  • Waardenburg syndrome
  • Neuroblastoma
  • Other conditions: congenital deafness, malrotation, gastric diverticulum, and intestinal atresia

Hirschsprung disease always involves the REcTum and is often associated with RET mutations.

• Hirschsprung 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 4^th and 7^th 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: ^[3]
  • Inability of the myenteric plexus to control the intestinal wall muscles → uncoordinated peristalsis and slowed motility
  • Spastic contraction of intestinal muscles → stenosis and functional obstruction
  • Expansion of the colon segment proximal to the aganglionic section (possible megacolon)
• Extent of the disease ^[2]
  • Ultra-short segment: limited to the distal rectum below the pelvic floor and the anus
  • Short-segment: limited to the rectosigmoid region (approx. 80% of cases)
  • Long-segment: involvement of the distal colon up to the splenic flexure (approx. 10% of cases)
  • Total colonic: entire colon (3–8% of cases)

Early presentation

• Delayed passage of meconium (> 48 hours)
• Distal intestinal obstruction: abdominal distention and bilious vomiting
• Digital rectal examination
  • Tight anal sphincter
  • Empty rectum
  • Squirt sign: explosive release of stool and air upon removal of the finger
• Palpation of feces via the abdominal wall

Late presentation ^[4]

• Chronic constipation with possible inability to pass gas
• Failure to thrive/poor feeding

Ultrashort-segment Hirschsprung disease ^[5]

• Definition: very short segment of aganglionosis, limited to the distal rectum
• Symptoms: less severe symptoms (e.g., chronic constipation)
• Treatment: usually treated with diet and stool softeners
• Prognosis: better prognosis with fewer complications

Total colonic aganglionosis ^[5]

• 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)

Imaging ^[1]

Abdominal x-ray

• Indication: usually performed initially in newborns with abdominal distention and delayed passage of meconium
• 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 (transition zone)
  • Retention of barium for 24–48 hours

Anorectal manometry ^[5]

• Goal: It 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
• Finding
  • Absent relaxation reflex of the internal sphincter after stretching of the rectum
  • Presence of high baseline resting pressures

Rectal biopsy ^[1]

• Indication: confirmatory test
• Procedure
  • Full-thickness biopsy under general anesthesia
  • Suction rectal biopsy
• Findings
  • Absence of ganglion cells in an adequate tissue sample
  • Elevated acetylcholinesterase activity
  • Hyperplasia of the parasympathetic nerve fibers
  • Absent calretinin immunostained fibers

In approximately 10% of newborns with Hirschsprung disease, no dilation or change in caliber is found in the colon contrast enema examination. Imaging and rectal biopsy are necessary to confirm the diagnosis.

Surgical correction ^[6]

• Objective: definitive treatment to remove the affected segment of the colon and bring the normal ganglionic intestinal ends together
• Procedures
  • Total transanal endorectal pull-through: preferred method that can be done in one stage ^[6]
  • Abdominoperineal pull-through (Soave procedure): traditionally 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.

Medical therapy ^[5]

• Objectives
  • Maintain normal fluid and electrolyte balance
  • Reduction of bowel distention
  • Prevent and manage complications
• Initial medical management
  • Intravenous fluid resuscitation
  • Nasogastric decompression
  • Intravenous antibiotics, if indicated
  • Colonic irrigation may be required.
• Postoperative medical management
  • Routine colonic irrigation
  • Prophylactic antibiotic therapy

If bilious vomiting

The differential diagnoses listed here are not exhaustive.

• Hirschsprung-associated enterocolitis ^[8]
  • Symptoms of toxic megacolon (e.g., abdominal pain, fever, foul-smelling and/or bloody diarrhea)
  • If not treated early, sepsis, transmural intestinal necrosis, and perforation are possible.
  • Management: IV fluid resuscitation, broad-spectrum IV antibiotics (anaerobic and aerobic coverage), rectal irrigations, with possible colostomy
• Fecal incontinence
• Urinary dysfunction
• Erectile dysfunction
• Peritonitis due to bowel perforation

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

• Good prognosis with early treatment ^[9]
• Higher mortality associated with younger age, length of aganglionosis, and preoperative enterocolitis ^[9]