Hirschsprung disease

Hirschsprung disease (congenital aganglionic megacolon) is an inherited disorder that primarily affects newborns. It is characterized by the absence of ganglion cells in the distal colon, leading to functional obstruction. The first manifestation of Hirschsprung disease is often failure to pass meconium within 24–48 hours of delivery, accompanied by signs of gastrointestinal obstruction such as bilious vomiting and abdominal distention. The onset and severity of symptoms vary based on the length of the aganglionic segment: A longer aganglionic segment is associated with early onset and severe disease. Diagnostic work-up involves x-ray, contrast enema, and, if initial studies are inconclusive, anorectal manometry. Diagnosis is confirmed with rectal biopsy. Initial management includes fluid resuscitation, correction of electrolyte imbalances, and bowel decompression. Definitive treatment involves surgical resection of the aganglionic segment. Hirschsprung-associated enterocolitis (HAEC) is a severe complication, which can manifest with fever, abdominal distention, and/or diarrhea. Without prompt treatment, HAEC can lead to toxic megacolon or sepsis. The prognosis for patients with Hirschsprung disease is good if treated at an early stage.

• 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)

For clinical features of HAEC, see “Complications of Hirschsprung disease.”

Neonates ^[4][5]

• Delayed passage of meconium (more than 24–48 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 due to constipation (nonspecific sign)

Infants and children ^[6]

• Chronic constipation, possibly with the inability to pass gas
• Growth faltering

Ultrashort-segment Hirschsprung disease ^[7]

• 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 ^[7]

• 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)

Approach ^[4][5][8]

• Obtain imaging (i.e., abdominal x-ray and contrast enema) to identify the site and severity of the obstruction.
• Perform anorectal manometry if initial studies are inconclusive.
• Confirm the diagnosis with a rectal biopsy.
• Obtain laboratory studies to assess for complications (e.g., sepsis) and guide management.

Laboratory studies

Laboratory studies may be obtained to assess for complications (see also “Approach to acute abdomen”).

• CBC
• BMP
• Blood cultures
• Emergency preoperative diagnostics: for critically ill patients requiring emergency surgery ^[5]

Imaging ^[4][8]

Abdominal x-ray

• Indication: initial study ; (along with contrast enema) in newborns with abdominal distention and delayed passage of meconium
• Findings
  • Decreased or absent air in the rectum
  • Dilated colon segment immediately proximal to a narrow aganglionic region
  • Distal intestinal obstruction

Contrast enema ^[4][9]

Contrast enemas can be diagnostic and therapeutic, as the contrast can lead to passage of obstructed stool. ^[10]

• Indication: initial study (along with abdominal x-ray) in most patients
• Contraindication: HAEC ^[11]
• Goals
  • Support diagnosis of Hirschsprung disease
  • Help determine the length of the aganglionic segment
  • Rule out differential diagnoses (e.g., intestinal atresia, meconium ileus, meconium plug syndrome)
• Finding: potential change in caliber between the normally innervated, proximal dilated bowel and the aganglionic, narrow distal bowel (transition zone)

A normal contrast enema cannot rule out Hirschsprung disease. ^[12]

Anorectal manometry ^[4][7][9]

Anorectal manometry is a diagnostic procedure used to assess anorectal function.

• Indication: atypical presentation (e.g., high clinical suspicion despite inconclusive findings on contrast enema), older children
• Findings: absent relaxation reflex of the internal sphincter after stretching of the rectum

Rectal biopsy ^[1][4]

• Indication: : to confirm the diagnosis in all children with suspected Hirschsprung disease, regardless of imaging findings
• Methods
  • Rectal suction biopsy
    • Does not require general anesthesia
    • Preferred for young infants
    • Multilevel suction biopsy: to assess the extent of the aganglionic segment for surgical planning
  • Full-thickness biopsy
    • Requires general anesthesia
    • Preferred for children more than 2–3 years of age
• Findings
  • Absence of ganglion cells in an adequate tissue sample
  • Elevated acetylcholinesterase activity
  • Hypertrophic nerve fibers
  • Absence of calretinin immunostaining

Perform a rectal biopsy in children with normal contrast enema or inconclusive findings if there is a high clinical suspicion for Hirschsprung disease. ^[1][4]

• Bowel obstruction (See “Causes of intestinal obstruction in neonates.”)
• Intestinal neuronal dysplasia
• Meconium plug syndrome
• Complications of cystic fibrosis, e.g., meconium ileus
• Congenital visceral malformations
  • Colonic atresia
  • Jejunal atresia
  • Duodenal atresia
• Intestinal malrotation and midgut volvulus
• Complications of necrotizing enterocolitis
• Congenital hypothyroidism

The differential diagnoses listed here are not exhaustive.

Initial management ^[4][5][8]

• Critically ill patients
  • Provide IV fluid resuscitation and correct electrolyte imbalances.
  • Place a nasogastric tube to decompress the bowel. ^[14]
  • Consult pediatric surgery for urgent colonic decompression if there is a concern for peritonitis or HAEC.
    • Perform rectal irrigation under specialist guidance.
    • Expedite emergency diverting ostomy if rectal irrigation is ineffective or complications of Hirschsprung disease occur. ^[4][15]
    • Obtain emergency preoperative diagnostics for patients requiring emergency surgery. ^[5]
• Stable patients: Consider rectal irrigation to decompress the bowel in consultation with pediatric surgery.
• All patients: Evaluate and treat HAEC and other complications of Hirschprung disease.

Surgery ^[4][8][9]

Surgery is a definitive treatment to restore normal bowel function.

• Procedures
  • Single-stage total transanal endorectal pull-through: preferred method in most infants with short-segment Hirschsprung disease
  • Abdominoperineal pull-through : performed in two stages
    • First stage: diverting colostomy or ileostomy for bowel decompression
    • Second stage: resection of the aganglionic segment and anastomosis between healthy bowel and the rectum
• Timing: typically delayed until operative conditions improve (e.g., after nutritional optimization and resolution of enterocolitis)
• Postoperative medical management
  • Regular colonic irrigation
  • Prophylactic antibiotic therapy
• Complications
  • Early: anastomotic leak
  • Mid-term to long-term: tight muscular cuff and/or anastomotic stenosis
  • General: constipation, fecal incontinence, postoperative HAEC ^[16]

Disposition ^[4][5][8]

• Critically ill patients
  • Consult pediatric surgery urgently for possible emergency surgery.
  • Admit to pediatric surgical inpatient unit or PICU.
• Stable symptomatic patients
  • Complications of Hirschsprung disease present: Admit to hospital.
  • Well-appearing patients without complications ^[8]
    • Consider discharge home with instructions for rectal irrigation to prevent fecal retention.
    • Follow up with pediatric gastroenterology
• All patients: Refer to pediatric surgery for definitive surgical treatment.

• Hirschsprung-associated enterocolitis (HAEC)
• Bowel obstruction
• Growth faltering ^[6]
• Urinary dysfunction ^[16][17]

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

HAEC can occur preoperatively and/or postoperatively and is the leading cause of morbidity and mortality in patients with Hirschsprung disease.

Risk factors ^[11][18][19]

• Down syndrome
• Long-segment Hirschsprung disease
• Prior HAEC
• Obstruction from any cause

Clinical features ^[11]

Symptoms and severity vary widely (from features of viral gastroenteritis to features of toxic megacolon).

• Classic features
  • Fever
  • Abdominal distention
  • Diarrhea
• Other possible features
  • Lethargy
  • Loose stools
  • Obstipation
  • Vomiting
  • Rectal bleeding

Diagnosis ^[11][18]

• Diagnosed based on clinical features of HAEC and findings of Hirschsprung disease on x-ray.
• See “Diagnosis of Hirschsprung disease.”

Contrast enema is contraindicated in HAEC due to the risk of perforation. ^[11]

Management ^[4][11][19]

• IV fluid resuscitation
• IV empiric antibiotics for intraabdominal infections
• Bowel decompression
  • Rectal irrigations
  • Surgical decompression (e.g., colostomy, ileostomy) may be needed for some patients.

Complications ^[4][11]

• Toxic megacolon
• Bowel perforation
• Sepsis

• Good prognosis with early treatment ^[20]
• Higher mortality associated with younger age, length of aganglionosis, and preoperative enterocolitis ^[20]