The editors and current authors would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Walton K.T. Shim. This current third edition chapter is a revision and update of the original author's work.
A 2 day old male infant presents with abdominal distention and bilious emesis. He has not passed meconium for the first 36 hours of life. He was born at term weighing 3.5 kg.
Exam: VS T 37.2 (rectal), P 125, RR 30, BP 75/55, weight 3.4 kg. He is an active hungry infant with a moderately distended and slightly firm abdomen. Bowel sounds are very active but not obstructive in nature. There is no hepatosplenomegaly or inguinal hernias. His anus is patent.
An abdominal x-ray series reveals large dilated loops of bowel with no air in the rectum. A hand injected contrast enema on the third day of life shows no distinct transition zone. A 24-hour delayed film shows retained contrast. A rectal mucosal suction biopsy is performed which reveals an absence of ganglion cells and the presence of hypertrophied nerve fibers consistent with a diagnosis of Hirschsprung disease.
Rectal irrigations are not successful in decompressing the colon. Surgery is performed to establish a descending colonic ostomy, placed under biopsy guidance. When the infant achieves a weight of 7 kg (15 pounds) a definitive resection will be performed.
Hirschsprung disease (also known as congenital megacolon or congenital intestinal aganglionosis) is a disease condition most commonly affecting the rectosigmoid portion of the colon. It presents with constipation in older infants and children, but mainly as abdominal distention, vomiting and delayed passage of meconium in newborn infants. The affected intestinal segment lacks ganglion cells which is required for normal peristalsis. Without these ganglion cells, normal peristalsis is lacking, resulting in a functional obstruction. This produces a proximal dilated colon and a distal normal appearing segment. Classically, there is an obvious transition zone where the dilated colon (with normal ganglion cells and peristalsis) meets the non-dilated colon (which is abnormal and aganglionic). The severity of Hirschsprung disease varies with the length of the involved segment and may be very difficult to diagnose especially in the ultra short segment disease because of the variability of the constipation. Total aganglionosis of the colon is quite uncommon and aganglionosis involving the small bowel is rare.
The incidence of Hirschsprung disease is about 1 in 5,000 births with a 4:1 predominance in males (1). There is a familial inheritance factor greatest among siblings but less common among children of parents with the disease. It is one of the most common causes of intestinal obstruction in the infantile period and is exceeded only by intestinal atresia, malrotation, and meconium ileus (in Caucasians). Hirschsprung disease mutations have been mapped to RET protooncogenes at 10Q11.2, the recessive EDNRB gene at 13Q22, its ligand endothelin 3 (EDN3) and glial cell line-derived neurotrophic factor (GDNF) in humans (2). Although the majority of cases are multigenic or multifactorial, there are some conditions associated with Hirschsprung disease such as Down syndrome, Waardenburg syndrome, neurofibromatosis, neuroblastoma, pheochromocytoma, the MEN2B syndrome, and others. The trypanosome causing Chagas disease is responsible for an acquired form of aganglionosis which may affect not only the colon but the esophagus and heart as well.
The diagnosis of Hirschsprung disease is suggested in a term newborn who has emesis and abdominal distention early in the newborn period. Since a newborn usually passes his/her first meconium on the first day, the most suggestive symptom is the lack of meconium passage during the first day of life. 99% of normal newborn infants pass stool within the first 48 hours of life (3). However, a minority of newborn infants with Hirschsprung disease will pass meconium within the first 48 hours of life, so passage of meconium should not exclude a diagnosis (2).
In the face of delayed meconium passage, vomiting, and abdominal distention, an abdominal X-ray series should be obtained. In congenital megacolon, intestinal dilatation is usually present with a gasless rectum. A hand injected contrast enema should be obtained to outline the rectum and sigmoid colon. Particular attention should be directed at not overfilling the intestines, thus obscuring the transition zone. A digital rectal examination is not recommended as it may prevent an accurate contrast enema study, although a temperature probe may be gently inserted to prove anal patency. Infants with Hirschsprung disease frequently retain contrast material longer than 24 hours and this delayed passage strongly suggests the diagnosis despite the absence of a definite transition area.
Although the gold standard for diagnosis is the histological absence of ganglion cells and hypertrophied autonomic nerves, the typical radiographic transition zone between the proximal dilated and distally narrowed colon is sufficient evidence for the diagnosis in the face of supportive presence of delayed meconium passage, vomiting, and distention. Histochemical patterns with special staining techniques have also been correlated with ganglion cell absence.
Occasionally an older child presents with a history of long standing constipation requiring enemas and other attentive measures directed at producing defecation. In such cases the diagnosis is made by contrast enema, as the transition zone is usually easily demonstrated. Contrast enemas in young infants may not be diagnostic or reliable (4). In these instances when clinical and radiographic findings are unable to make a definitive diagnosis, a rectal biopsy becomes necessary. A full thickness biopsy should have an absence of ganglion cells in Auerbach's plexus located between the circular and longitudinal muscle layers. Although ganglion cells are more plentiful in this area, the full thickness biopsy complicates later surgical dissection, so a rectal mucosal suction biopsy of Meissner's plexus located in the muscularis propria (i.e., performed more superficially and less invasively) is the preferred biopsy technique. Although ganglion cells are more sparse, the associated presence of hypertrophied nerve fibers is diagnostic.
Ganglion cells are absent in the most distal two centimeters of the normal rectum which is of importance when performing the biopsy and in the determination of an ultra short segment Hirschsprung case (i.e., the rectal biopsy should ideally be obtained proximal to this region).
There have been described a limited number of Hirschsprung patients with neuronal intestinal dysplasia that may explain continued post-operative morbidity. The diagnosis of neuronal intestinal dysplasia is not easily made but is associated with abnormal neural elements and their distribution in both the submucosal (Meissner's) and myenteric (Auerbach's) plexuses. This may explain some cases of continued post-operative constipation. Since ganglion cells are of neural crest origin, other conditions affecting the physiology, distribution, and migration of these cells may be related to Hirschsprung disease (5).
The normal physiologic pressure in the anal canal during defecation involves a decrease in internal sphincter pressure (relaxation) with rectal distention, thus allowing passage of the fecal bolus. In a baby with Hirschsprung disease, this relaxation of the involuntary internal sphincter does not occur, thus providing another means of making the diagnosis by anorectal manometry.
Surgical correction is the definitive treatment for Hirschsprung disease. Pre-operative anal dilations and rectal irrigations are also important in the clinical management of Hirschsprung disease. Once a diagnosis has been made, many infants will undergo dilations and irrigations at home until they are ready for surgery. This strategy can help infants with evacuation of stool and decrease the chance of enterocolitis pre-operatively, allowing the infant to grow prior to surgery. It has been shown that pre-operative anal dilations may help with surgery by shortening operation time (6). However, they may not make a difference in the incidence of enterocolitis post-operatively (6).
Surgical management of Hirschsprung disease involves resecting the aganglionic portion of the colon and reattaching the proximal ganglionic portion to the anal canal. There are three procedures commonly used by surgeons to do this. In the Swenson procedure, the distally narrowed colon is resected and the dilated segment is connected to two or three centimeters of distal rectum. In contrast, the Soave procedure involves stripping the mucosa from the distal aganglionic rectum and passing the normally innervated colon through the sleeve of the dysfunctional rectum (an endorectal pull-through) relying on the normal portion to propel through the abnormal cuff. Finally, the Duhamel operation incorporates a portion of the anteriorly placed aganglionic rectum with a posteriorly placed, normally innervated colon to produce a new rectum composed of half aganglionic and half ganglionic musculature (7).
Common to each procedure is post-operative enterocolitis characterized by abdominal distention, loose foul smelling stools (foul diarrhea), and vomiting. Abdominal radiographs will often demonstrate bowel obstruction characteristics such as bowel distention (smooth, hose-like bowel loops, air-fluid levels, etc.). The incidence of post-operative enterocolitis is estimated to be around 18% and does not differ significantly among the three procedures (8). Hirschsprung enterocolitis should be treated early and aggressively with rectal irrigations, anal dilatations, and intravenous support (2). Although fever and signs of infection may be present, stool cultures are often not helpful. Some surgeons routinely have parents or caregivers dilate the anus or irrigate the rectum post-operatively for several months to prevent enterocolitis and the formation of strictures at the anastomotic junction. Most patients continue to improve bowel function over time post-operatively; however, long-term complications such as fecal incontinence can impact quality of life for many patients (9). Children and adults previously treated for Hirschsprung disease often experience emotional and psychosocial problems related to post-operative complications that affect daily function (2).
Hirschsprung associated enterocolitis (HAEC) can be classified into three grades based on severity and diagnostic certainty. In grade 1 (possible HAEC), outpatient management is employed with oral metronidazole, oral electrolyte solution hydration, and rectal irrigation. In grade 2 (definite HAEC), symptoms are more severe and treatment consists of oral or IV fluid hydration, nasogastric decompression if there is abdominal distention, rectal irrigation to resolve fecal stasis, metronidazole, and potentially broad spectrum antibiotics. Children with grade 3 (severe HAEC) with shock should be treated in an intensive care unit with bowel rest, IV fluids, rectal irrigation, metronidazole, and broad spectrum antibiotics (10).
Questions
1. True/False: A digital rectal examination carefully performed is most important in the diagnosis of Hirschsprung disease in a newborn infant.
2. In the surgical management of Hirschsprung disease, what complication is common to the Swenson, Soave, and Duhamel procedures?
3. In a newborn infant with abdominal distention and/or vomiting, what is the most significant clinical finding to raise the suspicion of Hirschsprung disease?
4. True/False: In a child over a year of age with a radiographic transition zone, a rectal biopsy is required for a definitive diagnosis.
5. What cell line differentiates into Auerbach's and Meissner's plexus and may be responsible for other associated neurological defects?
References
1. Kliegman RM, St Geme JW, Blum NJ, et al. Chapter 358. Motility Disorders and Hirschsprung Disease. In: Kliegman RM, St. Geme JW, Blum NJ, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, Elsevier, Philadelphia, PA. pp:1955-1965.
2. Westfal ML, Goldstein AM. Diagnosing and Managing Hirschsprung Disease in the Newborn. NeoReviews. 2018;19(10):e577-e588.
3. Marcdante KJ, Kliegman RM, Schuh AM. Chapter 58. Assessment of the Mother, Fetus, and Newborn. In: Marcdante KJ, Kliegman RM, Schuh AM (eds). Nelson Essentials of Pediatrics, 9th edition. 2023. Elsevier, Philadelphia. pp:227-246.
4. Ambartsumyan L, Smith C, Kapur RP. Diagnosis of Hirschsprung Disease. Pediatr Dev Pathol. 2020;23(1):8-22. doi: 10.1177/1093526619892351
5. Holland AM, Bon-Frauches AC, Keszthelyi D, et al. The enteric nervous system in gastrointestinal disease etiology. Cell Mol Life Sci. 2021;78(10):4713-4733. doi: 10.1007/s00018-021-03812-y
6. Lin Z, Lin Y, Bai J, et al. Outcomes of preoperative anal dilatation for Hirschsprung disease. J Pediatr Surg. 2021;56(3):483-486. doi: 10.1016/j.jpedsurg.2020.05.008
7. Smith C, Ambartsumyan L, Kapur RP. Surgery, Surgical Pathology, and Postoperative Management of Patients With Hirschsprung Disease. Pediatr Dev Pathol. 2020;23(1):23-39. doi: 10.1177/1093526619889436
8. Hagens J, Reinshagen K, Tomuschat C. Prevalence of Hirschsprung-associated enterocolitis in patients with Hirschsprung disease. Pediatr Surg Int. 2022;38(1):3-24. doi: 10.1007/s00383-021-05020-y
9. Davidson JR, Kyrklund K, Eaton S, et al. Long-term surgical and patient-reported outcomes of Hirschsprung Disease. J Pediatr Surg. 2021;56(9):1502-1511. doi: 10.1016/j.jpedsurg.2021.01.043
10. Gosain A, Frykman PK, Cowles RA, et al. Guidelines for the Diagnosis and Management of Hirschsprung Associated Enterocolitis. Pediatr Surg Int 2017;33(5):517-521. doi:10.1007/s00383-017-4065-8
Answers to questions
1. False
2. Post-operative enterocolitis.
3. No passage of meconium in the first day of life.
4. False
5. Neural crest cells.