Differential Diagnosis of Hirschsprungs Disease at a University Teaching Hospital in South-West, Nigeria

Background: Hirschsprung’s disease is a common abdominal condition managed by paediatric surgeons. It is responsible for about 25% of all newborn intestinal obstructions. It’s diagnosis and recognition


Introduction
Hirschsprung's disease is characterized by absence of ganglion cells in the mysenteric and submucosal plexuses of the large bowel most of the time. It is relatively common and occurs in 1:5000 -1:7200 live births. [1] About 90% of infants with Hirschsprung's disease fail to pass meconium in the first 24 hours of life. [2] Although, most patients present in infancy and early childhood, some may not have symptoms until later in life. [2] The diagnosis is established in 15% within the first month of life, in 40-50% in the first 3 months, in 60% at one year of age and 85% by 4 years. [3] In developed countries, early presentation by patients ensure prompt diagnosis and intervention for the definitive treatment. [4] While in developing countries, late presentation with the attendant complications such as sepsis, intestinal perforation, necrotizing enterocolitis and intestinal obstruction further compound the diagnostic dilemma. [5] It is the most common cause of large bowel obstruction in the neonate as well as older children; occurring as an isolated condition in 70% of cases and may be associated with other congenital anomalies such as down's syndrome (trisomy 21) which is the most common chromosomal abnormality seen in about 10 percent of patients with hirschsprung's disease. [6,7] Other conditions that have been linked to hirschsprung's disease include congenital deafness, hydrocephalus, meckel's diverticulum, imperforate anus, ventricular septal defect, waardenburg's syndrome (pigment defects associated with deafness, neuroblastomas and ondine's curse (primary alveolar hypoventilation) [8,9].
Structural defects of the gastrointestinal tracts that resemble hirschsprung's disease include intestinal atresia, malrotation, volvulus, ano-rectal malformation and hypoplastic left colon syndrome. While functional and medical conditions with similar features as hirschsprung's disease are meconium ileus, meconium plug syndrome, drugs, electrolyte derangements, hypothyroidism and sepsis. [10] The differential diagnosis in newborn and older children pose serious clinical challenges in making a definitive diagnosis of hirschsprung's disease at presentation. A number of abdominal conditions which cause functional or mechanical intestinal obstruction could be easily excluded from hirschsprung's disease but conditions such as neonatal meconium ileus, meconium plug syndrome, distal ileal atresia and low imperforate anus often present diagnostic challenges in the first few days of life ( Figure  1). Hirschsprung's disease is a possible differential diagnosis in any child with an history of constipation regardless of age. However older children with motility disorders generally referred to as chronic idiopathic intestinal pseudo-obstruction present with similar symptoms and radiographic findings as hirschsprung's disease. These disorders are classified according to their histological characteristics into visceral myopathy, visceral neuropathy and Intestinal Neuronal Dysplasia (IND). [11][12][13] To confirm the diagnosis of hirschsprung's disease and differentiate it from the above mentioned conditions, diagnostic modalities such as plain abdominal x-rays, contrast enema (water soluble), anorectal manometry and rectal biopsy are employed towards achieving a definitive diagnosis and excluding other congenital abdominal conditions whose presentations resemble that of hirschsprung's disease. [14,15] This study was undertaken to identify the common abdominal conditions in children that simulate the clinical presentation of hirschsprung's disease which make the definitive diagnosis of hirschsprung's disease challenging.

Methodology
Information obtained from the recruited patients who presented with features of intestinal obstruction during the study period were entered into a structured proforma. These data included age at presentation, presenting complaints, duration of complaints prior to presentation to the paediatric surgical unit, findings on physical examination and results of investigations carried out were also documented, provisional diagnosis and histologically confirmed cases of hirschsprung's disease. Diagnostic modalities used to investigate these patients were plain abdominal radiograph, abdominal ultrasonography, barium enema and full thickness rectal biopsy.  Data Entry and Analysis: Data entry was done using word excel and analysis with SPSS version 23. The results were presented in the form of numbers and percentages, frequencies, bar charts and pie-charts.

Results
Three Hundred and Seventy-nine suspected cases of hirschsprung's disease were recruited for this study.  Out of these number of patients, 87 cases were confirmed histologically to have hirschsprung's disease and were further analyzed. 58 (66.6%) were males while 29 (33.4%) were females, a male to female ratio of 2-1. The patients were aged between 1 day and 16 years. 70 (80.4%) patients presented within one year of age. 17 (19.6%) patients presented beyond the age of one year. The prominent presenting complaints in the confirmed cases of hirschsprung's disease were delayed passage of meconium at birth 60 (69.1%). Other features present were infrequent bowel motion 12 (13.8%), progressive abdominal distension 7 (8.0%), vomiting 5 (5.7%), and failure to thrive 3 (3.4%) (Figure 4).

Discussion
Hirschsprung's disease results from a disturbance of the nervous system. It is attributed to aganglionosis or arrest of the cranio-caudal migration of the neural crest cells within the gastrointestinal tract. Usually classified as ultra short segment which affects the sphinteric region and classic hirschsprung's disease which is limited to the recto-sigmoid segment and accounts for 80% of cases. Long-segment disease accounts for the remaining 20% of aganglionosis which extends proximal to rectosigmoid region. Total colonic aganglionosis accounts for 3-10% of cases. Total intestinal aganglionosis may be seen in 1% of cases [10,16].
In our study, the most common differential diagnosis of hirschsprung's disease was neonatal sepsis, others were intestinal atresia, anorectal anomalies, duodenal atresia and pyloric stenosis. Similar observations to our findings have been made by some authors. [11,12] We had a predominance of male patients most of whom presented within one year of birth. This finding is in consonance with the reports of other researchers. [12,13] Most of our patients presented during infancy, however, some studies in Nigeria have reported predominant presentation of cases beyond the age of one year. [17,18] Complicated cases of hirschsprung's disease observed in our study were necrotizing enterocolitis, and intestinal perforation with peritonitis . Reports from other centres have found similar results. [19,20] The presence of associated congenital anomalies further worsened the diagnostic challenges as each anomaly presented with some typical features peculiar to that congenital malformation. The anomalies observed in our study were down's syndrome which has been reported as the commonest associated chromosomal anomaly of hirschsprungs disease, congenital heart disease and hypospadias. This is similar to the observations of other authors [20,21].
Misunderstanding of symptoms, findings on physical examination and diagnostic difficulties make hirschsprung's disease one of the most challenging diagnostic dilemmas in paediatric surgical practice. This is mainly due to different ways of interpreting the history, findings of physical examinations, results of investigative modalities and difficulties which arise as a result of its resemblance to other childhood acute and chronic abdominal conditions, complicated cases and associated congenital conditions especially those affecting the gastrointestinal tract which result to functional intestinal obstruction or mechanical intestinal obstruction. [22,23] The predominant symptoms in our study was delayed passage of meconium and infrequent bowel movement. Symptoms range from neonatal intestinal obstruction to chronic progressive constipation in older children. Eighty percent of patients present in the first few months of life with difficult bowl movements, poor feeding and progressive abdominal distension. Rectal examination may demonstrate a tight anal sphincter and explosive discharge of stool and gas (fountain sign). Although most patients present in infancy and early childhood, some may not have symptoms until later in life and common symptoms in older children include chronic progressive constipation, recurrent fecal impaction, failure to thrive and malnutrition. One third of patients with Hirschsprung's disease present with enterocolitis associated with diarrhea rather than constipation.
However, a study carried out in Kenya discovered chronic constipation (90%) and abdominal distension (90%) as their most common symptoms. Other symptoms reported in this study included repeated vomiting (48% of children) and failure to thrive (29%). [24] The disease usually present in infancy, although some patients present with persistent severe constipation later in life. Symptoms in infants include difficult bowel movements, poor feeding, poor weight gain, and progressive abdominal distension. Early diagnosis is important to prevent complications such as enterocolitis and colonic rupture. A rectal suction or full thickness biopsy can detect hypertrophic nerve trunks and the absence of ganglion cells in the colonic submucosa thus confirming the diagnosis [25].
The diagnostic challenges or dilemma are worse in our environment where there are limited resources, funds and facilities needed for initial and early confirmation of diagnosis of hirschsprung's disease. Added to these are the challenges of late presentation with the attendant complications and the nonavailability of facilities for frozen section which could improve the chances of achieving early and definitive diagnosis. [26] To resolve the diagnostic challenges and differential diagnosis, several diagnostic modalities were employed in our study to confirm the diagnosis of hirschsprung's disease and identify other conditions that simulate this disease. The diagnostic modalities employed were plain abdominal x-ray, barium enema using water soluble contrast medium, abdominal ultrasound, full thickness rectal biopsy and frozen section where available. Early presentation and diagnosis reduces the challenges caused by numerous differential diagnosis and improves outcome of management [27,28].

Conclusion
The peculiar ways of presentation of hirschsprung's disease and its resemblance to other acute and chronic abdominal conditions can pose a diagnostic dilemma to the surgeon. However, a high index of suspicion and use of the common imaging techniques and rectal biopsy would enhance early recognition, prompt diagnosis and quick intervention.