Case 2 -

Adult Hirschprung's Disease Wendy Frankel

Case History: A 26-year-old woman reported to the emergency department complaining of many years of constipation. She had previously been evaluated with colonoscopy, barium enema, and anal manometry, with all studies being reported as normal. Her mother confirmed a negative workup for constipation during a hospitalization at age 8 with slowly worsening symptoms since that time. There was no history of delayed passage of meconium. Her family history was remarkable for similar constipation symptoms of unknown origin in her mother and aunt. Upon physical examination she was emaciated with significant abdominal distention and tympany to palpation. Her abdominal skin showed evidence of chronic distention. Her laboratory studies were remarkable for an iron deficiency anemia and endocrine function tests were within normal. An AP portable view of the abdomen revealed extensive fecal retention throughout the colon. A CT scan confirmed severe colonic dilation along with extensive fecal loading and generalized colonic wall thickening. The rectum was markedly dilated and there was no obstructive lesion identified. Bowel rest, nasogastric tube decompression and daily enemas were effective over several days. Additional studies were then performed. Flexible sigmoidoscopy revealed a markedly distended colon. A small bowel follow-through showed displacement of the small bowel due to the distended colon with a delayed transit time. Anal manometry showed a lack of a normal recto-anal inhibitory reflex. Deep rectal biopsies were performed followed by a total proctocolectomy and ileal pouch anal anastomosis with diverting loop ileostomy. Pathologic findings The lumen of the entire colon was packed with firm solid fecal material. The colon was massively dilated, worse in the distal portion, with a maximal internal circumference up to 23 cm. The colonic wall was thickened, up to 1.0 cm. Case 2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer No ganglion cells were identified in the submucosa or between the muscular layers in the distal rectum and up to 5.7 cm from the anal-rectal junction. Hypertrophic nerve bundles were present in this region. Proximal to this aganglionic segment was a 2.6-cm hypoganglionotic segment or transitional zone where rare ganglion cells and associated thick nerves were seen. The rest of the colon and small bowel showed normal distribution of the ganglion cells. Discussion Hirschsprung's disease (HD) is a congenital aganglionosis of the submucosal (Meissner's) and myenteric (Auerbach's) neural plexuses principally affecting the rectosigmoid or rectal segments of varying length. Most cases become manifest during the neonatal period but, in rare instances, the disease is initially diagnosed in adults. In these cases, the patients have milder disease and go undiagnosed early in their lives because the proximal innervated colon can be hypertrophied and, thus, compensates for the distal obstructed, aganglionic rectum. In addition, these patients often try to relieve the constipation by taking cathartics and using enemas. Eventually the dilated colon is no longer able to propel the feces distally. These patients then develop rapidly worsening constipation or fecal retention. The first recorded observation of HD is credited to Frederick Ruysch, who published an autopsy report entitled "Enormis intestini coli dilatatio" in 1691. Nearly two centuries later, the disease was reported in 1888 by Hirschsprung. It was not until 1948 that its pathogenesis was recognized. Whitehouse and Kernohan documented the absence of ganglion cells in the myenteric plexus of Auerbach and the submucosal plexus of Meissner in all patients with true congenital megacolon. Their findings led to the development of an effective surgical treatment by Swenson and Bill in 1948. HD affects approximately one in 5,000 livebirths and usually presents in infancy and early childhood. Only a small number remain undetected after 5 years of age. Most cases of HD are felt to have a genetic basis, and HD is a complex multigene disorder with incomplete penetrance and variable associated anomalies. Mutations in greater than 11 genes have been implicated in HD, but mutations in one or more of these genes are only detected in about half of HD making it likely that other genetic and environmental factors are involved. The primary pathogenic defect is the absence of ganglion cells of the submucosal (Meissner's) and myenteric (Auerbach's) plexuses in the affected portion of the large bowel. The disease is thought to be the result of defective migration of ganglion cell precursors of the neural crest into the hindgut. Recent molecular studies have linked HD to defects in neural crest stem cell function. The aganglionic segment in HD remains persistently contracted, whereas the proximal segment retains its peristaltic function. As a result, there is work hypertrophy, eventual dilatation (megacolon), and sometimes perforation of the normally innervated colon. Adult Hirschsprung's disease The term "adult Hirschsprung's disease" has been arbitrarily applied by some investigators to cases in which the patient is older than ten years of age when the diagnosis is established. While others have defined adult HD as cases in which the diagnosis was made after age 18 or 19. Although case reviews in the English literature based on different diagnostic criteria have given different numbers of total cases, the clinical presentation, radiologic features, and pathologic findings have been similar among the various reports. Nearly 300 cases with at least some features of adult or adolescent HD have been documented. The typical adult patient with HD has a history of long-standing constipation since infancy or early childhood and the male to female ratio is approximately 4:1. Patient age ranges from 10 to 73 years old, and the average age is 24.1 years. Half of the patients are younger than 30. Other symptoms include abdominal discomfort, distention and abdominal pain. Physical examination frequently reveals palpable fecal masses. The patients tend to use cathartics, suppositories and enemas chronically to achieve bowel movements. Fecal incontinence is not a feature in the adult patient in contrast to infants. Rectal narrowing on barium enema is seen in three-quarters of the patients. However, in about 20% of the patients with adult HD, a dilatated colon without characteristic rectal narrowing, as seen in our patient, is demonstrated. This finding may be due to a short, or more commonly, an ultrashort diseased segment. The exact incidence of adult HD is unknown because those cases are frequently misdiagnosed or undiagnosed. The diagnosis of HD in the adult can be much more difficult than the diagnosis in early infancy. This is due to the rarity of the disease in adults and the higher incidence of short or ultrashort segment aganglionosis with relative mild symptoms during the early stage of the disease. As in the newborns, the diagnosis of HD in adults must be established by rectal biopsy showing absence of ganglion cells in the distal rectum. Rectal biopsy should be performed only after more common causes of constipation and megacolon have been ruled out. Constipation and acquired megacolon in adults may be due to neoplasm, volvulus, stricture, slow colonic motility, Chagas disease, anatomical or functional outlet obstruction, or idiopathic (non-Hirschsprung's) megacolon. Causes from external factors include dietary factors, medications, psychological factors, and systemic diseases. Whenever there is a reasonable doubt, manometric studies and biopsies are warranted. Diagnosis The diagnosis of HD rests primarily upon barium enema, anorectal manometry and rectal biopsy. The initial step is a barium enema study. The most reliable finding is a clear-cut zone of transition between the aganglionic distal segment, which is narrow or of normal caliber, and the dilated proximal colon with normal ganglion cells. The transition zone to the dilated segment is often characterized as "funnel-shaped" or "inverted cone." Other signs may include retention of barium and the mixing of barium and stool. Conventional radiography may demonstrate findings typically seen in most other low small bowel obstructions such as variable gaseous distension of the colon and small bowel, often with air-fluid levels. However, the colon is difficult to differentiate and gas is usually absent in the rectum. CT scan may therefore be more useful for better anatomic delineation. Anorectal manometry typically demonstrates no internal anal sphincter relaxation in response to rectal distension. The diagnosis is confirmed by the rectal biopsy. A biopsy from the narrowed segment shows absence of ganglion cells and may show hyperplasia and hypertrophy of nerve fibers, and an increased level of the enzyme acetylcholinesterase (AchE). The initial biopsy is typically a suction rectal biopsy. Diagnostic biopsies must be taken at least 1 to 1.5 cm proximal to the anorectal squamo-columnar junction and have sufficient submucosa. Multiple levels are typically evaluated to identify ganglion cells. Hypertrophic nerve fibers are observed in many cases and help establish the diagnosis. Some centers use frozen tissue to help identify abnormally thick and numerous AchE-stained nerve fibers. In the resection specimen, the Pathologist can then confirm the diagnosis, map the transitional zone and assess the proximal margin of the resection for ganglion cells. Conclusion Adults with HD may present in an atypical fashion with massive dilatation of the entire colon without rectal narrowing. The diagnosis may be easily overlooked or misdiagnosed in adult patients with chronic constipation, particularly in the rare individual with ultrashort HD such as our patient. Therefore, all patients who have severe chronic constipation since birth or childhood need a thorough evaluation to rule out HD. The diagnosis can be suspected by barium enema and manometry, and confirmed by rectal biopsy. Making the diagnosis of HD is extremely important since surgical management is effective with satisfactory long-term functional results and significantly improved quality of life. Acknowledgment: Fayu Chen, MD, at the Ohio State University assisted with the case diagnosis and the handout. References Anuras S, Hade JE, Soffer E: Natural history of adult Hirschsprung's disease. J Clin Gastroenterol 1984;6:205-210. 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