Hirschsprung Associated Enterocolitis

What is Hirschprung’s Disease?

Hirschprung’s Disease (HD) is caused by the failure of neural crest cells to migrate completely during intestinal development.

The neural crest cells are progenitor cells for the enteric nervous system, which controls peristalsis, blood flow to the gut and secretions. The enteric ganglia are interconnected to form 2 plexi that extend along the length of the bowel: an out myenteric (Auerbach) plexus running the full length of the gut and an inner submucosal (Meissner) plexus, found in the small and large intestine. The absence of these plexi results in an aganglionic segment of the colon, which fails to relax, causing a functional obstruction.

Interestingly, the timing of the arrest in migration of the neural crest cells influences the severity of the disease. The cells migrate in a craniocaudal fashion. Therefore, early arrest results in a longer segment of aganglionosis.

The incidence of HD is 1 in 5000 live births. The male-to-female ratio is 4:1 in short-segment disease, but it is 1:1- 2:1 in long-segment disease.

How do children with Hirschprung’s present?

How these children present depends on whether they have short or long-segment disease. Short-segment disease only involves the rectosigmoid colon and accounts for 80-85% of cases. In long-segment disease, the aganglionosis extends proximally to the sigmoid colon.

Those with long-segment disease are more severely affected and tend to present earlier, usually in the first few days after birth. They can present with any of the following features:

• Abdominal distension
• Bilious vomiting
• Delayed passage of meconium
• Enterocolitis

Those with short-segment disease may present later in childhood with constipation and failure to thrive.

What is “delayed” passage of meconium?

There is a big variation in the timing of the first meconium passage in neonates; however, most healthy newborns will pass stool within the first 24 hours, and all healthy newborns should pass their first stool within 48 hours.

Clark studied 395 term infants and found that 98.5% passed stool within the first 24 hours and 100% within 48 hours.

It is generally acknowledged that term infants who don’t pass stool within the first 48 hours should undergo careful evaluation and investigation. 60-90% of patients with HD will not pass meconium within 48 hours.

The differentials of delayed passage of meconium are listed below:

• Meconium plug syndrome
• Meconium ileus
• Hirschsprung’s disease
• Anorectal malformation
• Intestinal atresia
• Malrotation, volvulus
• Hypoplastic left colon syndrome
• Opioid use
• Hypothyroidism
• Sepsis
• Prematurity, low birth weight

Hirschprung Associated Enterocolitis

Hirschsprung Associated Enterocolitis (HAEC) is a serious complication of HD. Patients can present critically unwell with haemodynamic instability, fever, vomiting, explosive diarrhoea and abdominal distension. An explosive release of gas or stool during rectal examination strongly supports a diagnosis of HD.

The incidence of HAEC ranges from 6-60% before pull-through surgery and 25-37% after surgery. HAEC can be potentially life-threatening. Swenson was one of the first to report on mortality in HAEC, reporting a mortality rate of 33% after HAEC, compared with 4% in HD patients without EC. The reported mortality in other studies varies greatly from 0 to 39%.

Mortality rates have improved in recent years, most likely due to improved supportive care in PICU and improved surgical expertise. The mortality rate in HAEC is now 1%.

Poor prognostic factors are HAEC present at diagnosis of HD and postoperative HAEC.

While it can be seen in all children with HD, several features appear to be associated with an increased risk:

• Trisomy 21
• Long-segment disease
• Previous HAEC
• Post-op obstruction

The cause of HAEC is unknown. Several hypotheses have been proposed:

• Dysbiosis of the intestinal microbiome
• Impaired mucosal barrier function
• Altered innate immune response
• Bacterial translocation

Mild cases can present with symptoms of viral gastroenteritis, fever, mild abdominal distension and diarrhoea. If it is not promptly recognized and treated, it can progress to toxic megacolon, which can be fatal. 

It is important to remember that HAEC can also occur in children who have had surgical repair for HD. It is due to obstruction, which can be due to:

• Retained aganglionosis
• Transition zone pull-through
• Dysmotility following pull-through
• Anastamotic stricture

A high index of clinical suspicion is required to make the diagnosis. Abdominal x-rays are also helpful and usually show significantly dilated bowel loops and air-fluid levels.

HAEC is an emergency. Prompt treatment is required with IV antibiotics (e.g metronidazole, gentamicin, amoxicillin) fluid resuscitation and surgical evaluation, which may include rectal washouts or an emergency colostomy.

Which children with constipation do we need to worry about?

Constipation is a very common presentation to ED. When assessing these patients, it is important to screen for any underlying abnormalities, including HD.

Constipation, with the following features, should raise your suspicions about undiagnosed HD:

• Neonates
• History of delayed passage of meconium
• Chronic, refractory constipation
• Failure to thrive
• Presence of other urogenital abnormalities
• Family history of HD (the risk for a sibling is 200 times higher than the general population, (4% vs. 0.02%)
• Associated syndromes:
  • Down Syndrome
  • Bardet-Biedl syndrome
  • Cartilage-hair hypoplasia
  • Congenital central hypoventilation syndrome
  • Multiple endocrine neoplasia type 2
  • Mowat Wilson syndrome
  • Smith-Lemli-Opitz syndrome
  • Waardenburg syndrome

How is Hirschprung’s diagnosed?

An abdominal X-ray may show dilated or thickened bowel loops or air-fluid levels. These findings, however, are non-specific.

The contrast enema is useful for demonstrating the functional obstruction seen with HD, as seen in the film below.

Definitive diagnosis is by rectal suction biopsy.

It is important to consider HD in children presenting to ED with constipation. You should have a low threshold for surgical referral, particularly if they have any risk factors listed above.

How is Hirschprung’s treated?

Treatment involves surgical resection of the aganglionic segment and anastomosis of the normal bowel to the anus while preserving sphincter function.

Long-term complications include:

• Chronic constipation
• Incontinence
• Recurrent HAEC
• Psychosocial issues

Did you know?

HD was first described by Harald Hirschsprung in 1886. He described two children with severe constipation due to dilation and hypertrophy of the colon.

Lennander, in 1900, was the first to suggest that the pathogenesis may be neurogenic in origin. Tittel then demonstrated, in 1901, histological findings indicating aganglionosis of the colon. In 1948, Swenson used motility studies to demonstrate the absence of peristalsis in the aganglionic colon.  

The history of Hirschsprung’s Disease is an interesting and colourful one with many false starts and conflicting opinions. If you’re interested in reading more, look no further than this American Academy of Surgeons history of surgery article.

References

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5. Clark DA. Times of First Void and First Stool in 500 Newborns [Internet]. Vol. 60, PEDIATRICS. 1977 [cited 2020 Jul 28]. Available from: www.aappublications.org/news

6.Loening-Baucke V, Kimura K. Failure to Pass Meconium: Diagnosing Neonatal Intestinal Obstruction. Am Fam Physician. 1999 Nov 1;60(7):2043.

7. Gosain A, Frykman PK, Cowles RA, Horton J, Levitt · Marc, David ·, et al. Guidelines for the diagnosis and management of Hirschsprung-associated enterocolitis. Pediatr Surg Int. 2017;33:517–21.

8. Swenson O, Davidson FZ. Similarities of Mechanical Intestinal Obstruction and Aganglionic Megacolon in the Newborn Infant. N Engl J Med [Internet]. 1960 Jan 14 [cited 2020 Jul 28];262(2):64–7.

9. Vieten D, Spicer R. Enterocolitis complicating Hirschsprung’s disease. Semin Pediatr Surg. 2004 Nov 1;13(4):263–72.

10. Murphy F, Puri P. New insights into the pathogenesis of Hirschsprung’s associated enterocolitis. Pediatr Surg Int [Internet]. 2005 Oct 30 [cited 2020 Jul 28];21(10):773–9. Available from: https://link-springer-com.proxy.library.rcsi.ie/article/10.1007/s00383-005-1551-1

11. Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet [Internet]. 1990 [cited 2020 Jul 20];46(3):568–80. Available from: /pmc/articles/PMC1683643/?report=abstract

12. Hirschsprung disease • LITFL • Medical Eponym Library [Internet]. [cited 2020 Jul 20]. Available from: https://litfl.com/hirschsprung-disease/