Hirschsprung’s Disease

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Hirschsprung’s disease\: congenital intestinal motility disorder a
of the distal large intestine, typically rectosigmoid.
Aetiology\: due to disrupted craniocaudal migration of neural crest cells (NCCs) during the
to reach the distal gut and di
Pathophysiology\: lack of enteric innervation leads to tonic contraction of the aganglionic segment, causing functional
colonic obstruction and secondary dilation of proximal healthy colon.
Subtypes\: short segment (80% - rectosigmoid), long segment (15-20% - extends to splenic
colonic aganglionosis (5% - entire colon).
Risk factors\: male sex (4-fold higher risk), family history (10%), chromosomal associations (Down's syndrome, Waardenburg
syndrome, MEN2a).
Clinical features\: neonatal triad (failure to pass meconium in 24-48 hours, abdominal distension, bilious vomiting); chronic
constipation, faltering growth, malnutrition, feeding di
60% of patients.
Hirschsprung-associated enterocolitis (HAEC)\: severe complication and major cause of mortality; presents with pyrexia,
abdominal tenderness, foul-smelling or bloody diarrhoea.
Examination
rectal vault with "blast sign" on digital rectal examination.
Investigations\: rectal biopsy (absence of ganglion cells, hypertrophic AChE-positive nerve
investigations, ABG, serum electrolytes, TFTs); imaging (abdominal X-ray, barium studies, anorectal manometry).
Management\: initial stabilisation, treatment of HAEC (antibiotics,
removal of aganglionic segment and pull-through of healthy bowel; routine colonic irrigation pre-surgery.
Complications\: general (HAEC, bowel perforation); post-operative (early\: wound infection, pelvic abscess, anastomotic
leaks; late\: HAEC, constipation, faecal incontinence, bladder/sexual dysfunction).
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A comprehensive topic overview

Introduction

Hirschsprung’s disease is a congenital intestinal motility disorder a
It is characterised by aganglionosis of the distal large intestine. The absence of enteric ganglion cells is commonly limited
to the rectosigmoid segment but may extend proximally beyond the sigmoid colon.
Subsequently, the denervated length of the colon fails to undergo peristalsis and functional colonic obstruction occurs.
1

Aetiology

In Hirschsprung’s disease, aganglionosis occurs due to disrupted craniocaudal migration of neural crest cells (NCCs)
during the
into enteric ganglion cells.
2Genetic studies have discovered at least 24 genes, whose mutations could lead to defective migration and di
NCCs. The gene commonly implicated is the receptor tyrosine kinase (RET) gene, mutations of which have been noted in
up to 35% of sporadic cases and 50% of familial cases.
2,3
Pathophysiology and subtypes
The lack of enteric innervation l eads to tonic contraction of the aganglionic segment. This leads to a lack of e
peristalsis and failure of the internal anal sphincter to relax.
These events result in functional colonic obstruction. Intestinal contents such as faeces accumulate and subsequently
secondary dilation of the more proximal healthy innervated colonic tissue occurs.
3,4
Due to the variable nature of the length of aganglionosis, there are three main anatomical subtypes of Hirschsprung’s
disease\:
2,3
Short segment\: commonest subtype, seen in ~80% of patients where aganglionosis involves only the rectosigmoid
segment
Long segment\: the aganglionosis extends proximally beyond the sigmoid colon, typically to the splenic

Total colonic aganglionosis\: seen in ~5% of patients, where the entire colon is involved

Risk factors

The following risk factors are associated with an increased likelihood of developing the condition\:
4,5
1. Male sex\: males have a four-fold higher risk than females of developing Hirschsprung's disease. However, where the entire
colon is involved the sex ratio nears 1\:1.
2. Family history\: 10% of patients have a positive family history, although most cases are sporadic.
3. Chromosomal associations\: found in up to 32% of patients, with the commonest association being Down's syndrome. Other
rarer associations include Waardenburg syndrome and multiple endocrine neoplasia type 2a (MEN2a).

Clinical features

The majority (75%) of cases present during the neonatal period. The severity of symptoms may vary depending on the
length of the aganglionic segment.
2
History
During the neonatal period, the typical triad of symptoms of Hirschsprung’s disease is\:
4
Failure to pass meconium within the
Abdominal distension
Bilious vomiting
In practice, however, only 26% of patients present with all three features. 4
feeds and feeding intolerance.
Other symptoms include irritability,
“spitty’’ after
For patients who present later in life, clinical features include\:
1,4
History of chronic constipation since birth, which may be associated with over
Faltering growth
Malnutrition
Lethargy
Feeding di
Furthermore, for all age groups, a thorough systems review is required as associated congenital anomalies in other body
systems (e.g. ophthalmological, neurological, and cardiac) have been noted in up to 60% of patients.
3
Hirschsprung-associated enterocolitisHirschsprung-associated enterocolitis (HAEC) is a severe complication of Hirschsprung’s disease and is the most
signi
Although the exact pathophysiology is unknown, the commonly accepted hypotheses can be remembered as the
"3Ds"
\:
Dysmotility
Dysbiosis of the gut microbiome
Defective intestinal barrier function and mucosal immune response
Enterocolitis can occur both before de
Hirschprung's disease could be with HAEC.
2
HAEC should be suspected in a child presenting with pyrexia, abdominal tenderness, foul-smelling or bloody
diarrhoea, and features of Hirschsprung’s disease.
6
Clinical examination
For patients who present early before the onset of HAEC, typical clinical
2,3
Abdominal examination\: grossly distended abdomen, faecal mass in the left lower quadrant, tympanic percussion note
(due to intestinal distension), increased bowel sounds (a sign of early obstruction) which may progressively decrease in
frequency
Digital rectal examination\: normally placed patent anus (allowing passage of
empty rectal vault, withdrawal of the examining
due to dramatic rectal decompression.
If the patient presents with HAEC, it is important to look for clinical manifestations of underlying hemodynamic instability
such as hypovolemia, hypotension or sepsis.

Di

Due to the non-speci
be divided into two categories based on the age of presentation.
2,4
Table 1. Di
Neonates Older children
Meconium obstruction (e.g. meconium
plug syndrome, meconium ileus)
Intestinal atresia
Intestinal malrotation with volvulus
Anorectal malformations (e.g.
imperforate anus, anal stenosis)
Small left colon syndrome
Prematurity
Functional constipation
Hypothyroidism

Investigations

Rectal biopsy
If there is no evidence of HAEC, the diagnosis of Hirschsprung’s disease can be con
with acetylcholinesterase (AChE) staining.
The diagnosis requires the histopathological demonstration of\:
2,5
Absence of colonic ganglion cellsPresence of hypertrophic (> 40 micrometres) AChE-positive nerve
Figure 1. Rectal biopsy demonstrates the
lack of ganglion cells and hypertrophied
submucosal AChE-positive nerve
(stained brown).
A suction rectal biopsy (which can be performed in the outpatient setting), is usually adequate for diagnosis. An alternative
method is a full-thickness biopsy performed under general anaesthesia.
Indications for rectal biopsy (NICE)
According to NICE guidelines, a rectal biopsy is only indicated if one or more of the following are present\:
7
Failure to pass meconium within 48 hours following birth in term infants
Constipation since the neonatal period
Chronic abdominal distension associated with vomiting
Family history of Hirschprung’s disease
Failure to thrive/ growth faltering along with any of the above features
Laboratory investigations
If the clinical presentation is ambiguous for Hirschsprung’s disease or the patient presents critically unwell or with clinical
features of HAEC, additional relevant laboratory investigations include\:
Full blood count\: leukocytosis should raise suspicion for Hirschsprung’s associated enterocolitis or sepsis
Sepsis investigations\: blood cultures, serum lactate test, CRP, urinalysis and culture if the clinical suspicion for sepsis is
high
Arterial blood gas\: if indicated (e.g. low SpO2) to assess the degree of hypoxia
Serum electrolytes\: to rule out electrolyte imbalances such as hypercalcemia and hypokalemia which can cause
constipation or aggravate it
Thyroid function tests\: to exclude hypothyroidism
Imaging
Relevant imaging investigations include\:
Abdominal X-ray\: can reveal features indicative of distal intestinal obstruction (Figure 2). These include air-
distended proximal bowel loops (predominantly colonic) and absence of rectal gas.
2
Barium studies\: performed after the abdominal X-ray, for identi
distal bowel and dilated proximal bowel, and the classical “saw-tooth” appearance of the aganglionic segment (Figure
3). Useful in approximating the length of the aganglionic segment for the surgeon.
1,3Figure 2. Supine abdominal X-ray showing multiple loops of dilated bowel.
Figure 3. X-ray post-barium enema demonstrates a transition point between the sigmoid and descending colon with a saw-tooth
appearance of the sigmoid colon.Other investigations
Other relevant investigations include\:
Anorectal manometry\: the inability to elicit relaxation of the internal anal sphincter in response to distension of the
rectum with the balloon is typically seen in Hirschsprung’s disease.
2

Management

Initial management
The initial management of Hirschsprung’s disease depends on haemodynamic status, hydration status and any evidence
of underlying HAEC.
If the patient is unwell, treatment should focus on stabilising the child
intravenous .
Should the child present with features of HAEC, then prompt recognition is vital to prevent disease progression to toxic
megacolon, bowel rupture and bacterial sepsis.
Treatment of HEC involves intravenous broad-spectrum antibiotics (e.g. metronidazole),
colonic irrigation, nasogastric/orogastric bowel decompression and making the patient nil-by-mouth for complete bowel
rest.
In addition, the sepsis six care bundle should be initiated within an hour after presentation should sepsis have already
developed secondary to HAEC.
2,6
De
The de
pull-through of the proximal healthy bowel down to the anal canal with preservation of sphincter function.
Routine colonic irrigation is performed daily following diagnosis to bridge the gap to surgery. Typically, patients receive one
to three daily irrigations using 10-20mL of normal saline solution to wash out the intestinal contents. 2
Irrigation is vital in
preventing enterocolitis due to bacterial overgrowth resulting from faecal stasis.
5
Three types of pull-through surgical techniques exist\:
4
Swenson
Duhamel
Soave
Consultation with the paediatric surgical team is essential to decide the type of pull-through method and the timing of
surgery for the child.
2

Complications

General complications of Hirschsprung’s disease include\:
Hirschsprung associated enterocolitis (HAEC)
Bowel perforation
Post-operative complications can be divided into early and late complications.
5,8
Table 2. Post-operative complications related to Hirschprung's disease
Early post-operative complications Late post-operative complicationsWound infection
Pelvic abscess
Anastomotic leaks
HAEC
Constipation
Faecal incontinence
Bladder dysfunction
Sexual dysfunction

References

Lissauer T, and Carroll W. Illustrated textbook of paediatrics. 6th Edition.2022. Elsevier Science. Chapter 14 (p 257-258).
BMJ Best Practice. Hirschsprung’s disease. Available from\: [LINK]
Thakkar H, Curry J. Hirschsprung’s disease. Paediatrics and Child Health. 2020;30(10)\: 341-344.
Kliegman R, St. Geme J, Blum N, Schor N, Behrman R, and Nelson W. Nelson textbook of pediatrics. 21st Edition. 2020.
Elsevier. Chapter 358.
Lotfollahzadeh S, Taherian M, Anand S.Hirschsprung Disease.Statpearls [Internet]. Treasure Land (FL)\: Statpearls Publishing;
2022 Jan. Available from\: [LINK]
Lewit RA, Kuruvilla KP, Fu M, Gosain A. Current understanding of Hirschsprung-associated enterocolitis\: Pathogenesis,
diagnosis and treatment. Semin Pediatr Surg. 2022;31(2)\:151162.

NICE. Constipation i n c h i l d r e n a n d y o u n g p e o p l e \: d i a g n o s i s a n d m a n a g e m e n t .2010. Available from\: [LINK]
Hagens J, Reinshagen K, Tomuschat C. Prevalence of Hirschsprung-associated enterocolitis in patients with Hirschsprung
disease. Pediatr Surg Int. 2022;38\:3-24.
Attention De
Autism Spectrum Disorder (ASD)
Image references
Biliary Atresia
Figure 1. Marvin 101. H i s t o p a t h o l g y o f H i r s c h s p r u n g’ s d i s e a s e . Licence\: [CC BY-SA 3.0]
Bronchiolitis
Figure 2. Dr Hani Makky Al Salam. From the case rID\: 7570. License\: [CC BY-NC-SA]
Figure 3. Dr Hani Makky Al Salam. From the case rID\: 7570. License\: [CC BY-NC-SA]
Cerebral Palsy

Reviewer

Test yourself

Dr Khor Shed Peng
Senior Lecturer, Paediatrician, Monash University Malaysia