Hirschsprung’s disease is a fairly common pediatric surgical issue, affecting 1 of 5,000 births in the United States. The disease impacts gastrointestinal motility because of a lack of ganglion cells in the colon. It is characterized by delay of passage of meconium, poor feeding, abdominal distension, and difficulty with bowel movements. Ganglion cells (nerve cells) are necessary for the process of intestinal motility. Any changes in the microenvironment can lead to the neural crest cells from developing into myenteric ganglion cells (Phillips, Samuel, Woosley, & Mclean, 2013). In the case of eosinophilic myenteric ganglionitis (EMG), the ganglion cells are infiltrated by eosinophils, leading to bowel dysmotility and, if left untreated, intestinal pseudo-obstruction (Behjati et al., 2009).
This case will show the nutrition complications an infant or child can experience as a result of Hirschsprung’s disease complicated by a concurrent diagnosis of EMG. The pediatric registered dietitian (RD) is an integral member of the team that can assist in managing these issues. Areas such as growth, a review of the decision process for formula and food selection, and nutritional management of constipation will be reviewed. The case will highlight that variable yet significant nutrition issues can be present both postoperatively and long term as the child grows and develops.
“PJ” is a former term male infant who failed to pass meconium and developed bilious emesis on the first day of life. He underwent a suction rectal biopsy that revealed the absence of ganglion cells consistent with Hirschsprung’s disease (HD). He was taken to the operating room at the seventh day of life for a laparoscopy with planned endorectal pull-through procedure. The transanal open rectal biopsy showed agangliosis on a frozen section analysis. A sigmoid colostomy and mucous fistula were created. A mucous fistula is formed when two ends of the bowel are brought to the surface of the abdomen. One is formed to allow feces, and the other allows mucous to be released. His final postoperative pathology report indicated absence of ganglion cells in the anorectal mucosa but some eosinophils (greater than 10 cells/hpf) in the myenteric plexus (a network of nerve fibers that supply the gastrointestinal tract and control gastrointestinal (GI) motility) and surrounding smooth muscle of the transition zone, aganglionic sigmoid colon, and rectum. These findings are consistent with diagnosis of EMG. At 3 months old, he had an open transanal biopsy before surgery to confirm the diagnosis of HD, which did show a lack of ganglion cells.
At 6 months old, he had a Soave endorectal pull-through with resection of the affected colon. Postoperatively, he had a significant complication of persistent explosive diarrhea, which led to severe excoriation of his buttocks and bleeding despite regular application of skin barrier cream. It was significant enough to where his hospital discharge was delayed by 2 weeks. He continued to have up to 8–10 loose watery stools daily when the pediatric RD was first asked to evaluate him in pediatric surgery clinic when he was 8 months old. His symptoms improved with change to a specialized diaper cream, addition of loperamide, and adjustments in his infant formula made by the dietitian (outlined below). He had a rectal examination with rectal dilatation under anesthesia at 13 months old and again at 15 months old, which showed a rectal stricture, indicating need for more home rectal dilations. Biopsies taken during this procedure showed no further eosinophilic infiltrates in the bowel biopsy.
PJ is now 3 years old and continues to be peripherally followed by pediatric surgery but has transitioned over to the pediatric gastroenteroloy service for issues of chronic constipation with need for fairly frequent GI cleanouts. His overall growth has been quite good, he is eating a relatively varied diet with exception of milk, and he has had no issues with behavioral or physical development.
The outpatient pediatric dietitian was first consulted to see PJ when he was 8 months old, because of lagging weight gain and significant watery diarrhea stools after his Soave pull-through with colon resection. When he first presented to the RD, he was consuming a semielemental, reduced lactose infant formula, and they had trialed multiple other formulas before and after this without seeing much improvement. He was consuming two-to-three jars of Stage 1 baby food daily as well. He was having 8–10 watery loose stools daily and only occasional vomiting.
As his stool output was significant and his buttocks were severely excoriated, the decision was made to change over to an amino-acid-based infant formula. He returned 2 months later and had experienced a rapid improvement with this change. His stool output was now two-to-three soft, fairly formed stools on this new formula, his buttocks breakdown had healed, and an improved weight gain trend was noted. His growth had been somewhat flat when we first met PJ, and at follow-up, he had an improvement in his growth velocity with an average daily weight gain of 18 grams per day, which is ideal for his age. Mother was slowly increasing his variety of soft solids in diet, and thus far, the only foods that appeared to change stools to a loose consistency were those with milk.
As he was approaching a year, the RD transitioned PJ over from an infant amino acid formula to a toddler amino acid formula. He liked this very much and actually had an issue of ingesting too large of a quantity that led to greater than desired weight gain and limitation of other foods in diet (this is an uncommon occurrence with an amino-acid-based formula). There was also a mild complication involving formula mixing errors during the transition that led the formula to be too hypercaloric, which led to a temporary increase in his stool output. This was easily resolved with education, and he consumed an average of 24 ounces per day of his formula (vs. 30–40 ounces per day initially). He continued to expand his oral diet of solids, and the RD spent time with parents at each visit reviewing dietary intake, as the mother tried to avoid foods containing milk. She noticed an increase in gas and stools despite limiting milk products in foods especially when he consumed commercially packaged foods. When we examined his diet recall in more detail, the decision was made to try an empiric trial of eliminating soy in diet as well. This proved to be helpful and resulted in a decrease in gas and loose stools.
As PJ has grown, he developed increasingly frequent issues of constipation with crying and stomach pain before and during passing a stool. Upon examination, it was found that the mother had periodically challenged him during this time with some foods containing dairy and soy and found that these foods resulted in abdominal pain and loose stools with some urgency. On the basis of this, she continued to avoid foods containing dairy and soy and found substitutions for these foods with the dietitian’s guidance. She also tried to incorporate higher fiber foods and optimal fluids in his diet. Because she noticed him developing increased symptoms of gastroesophageal reflux (some early satiety, frequent burping, reswallowing), the pediatric GI team began to follow PJ regularly for management of gastroesophageal reflux (GER) and constipation as an outpatient. As his growth and overall variety in his diet was quite good (tracking at the 50th percentile; see Table 1), he was trialed off of the amino-acid-based toddler formula and on coconut and almond milk as substitutes. He would not accept the coconut milk but did like the almond milk. However, he developed an increase in loose stools after about a week of consuming this, so the decision was made to place him back on his toddler amino acid formula. He remains on his toddler amino-acid-based formula.
In total, the pediatric outpatient dietitian saw PJ 12 times in a time frame of 20 months (ages 9 months–3 years). He continues to drink his amino-acid-based toddler formula and has transitioned off of a bottle and on to a sippy cup and, most recently, an open cup in this time frame. Parents are regularly counseled on use of fiber in diet to help manage his constipation as well as label reading to look for products containing milk. He has been able to tolerate small amounts of soy in the diet. He saw the pediatric allergy service at the age of two years who assessed serum-specific immunoglobulin E (IgE) levels of milk and soy. The soy was unremarkable with a value of 1.11 kUA/L (range < 0.35), and the milk was 5.67 kUA/L (range < 0.35). It was recommended at that time (age of 22 months) that he could slowly introduce soy into his diet but should continue to avoid milk protein ingestion. It was also recommended that he return to allergy clinic 6–9 months to perform skin prick testing with repeat immunoglobulin E levels. This has not yet been completed.
His most recent nutrition counseling at 3 years old included a discussion of balanced nutrients in the diet because of consumption of a disproportionate amount of sweets and low-nutrient-dense foods. As always, the RD spent time reinforcing ongoing adequate fluid intake with increase of fiber in the diet and continued troubleshooting issues related to expanding his oral diet (managing his milk sensitivity in daycare, family functions, label reading). He unfortunately has had ongoing issues with constipation and needs frequent enemas and GI cleanouts to manage this despite regularly using a stool softener and reports of following a high-fiber diet. Despite these issues, PJ’s overall growth is excellent, and he continues to grow along the 50th percentile for all growth parameters.
NUTRITION TEACHING POINTS
Formula Selection Process
One example of how the pediatric dietitian can serve as an invaluable member of the pediatric surgery team is when it is time to decide a course of action for infant or toddler formula selection. Although breastfeeding is always considered the “gold standard,” there are various reasons why some babies may receive infant formula in its place. There are numerous choices within each formula company that all promote various benefits, and the vast amount of options can become overwhelming to both the parent and the practitioner.
In this particular instance, PJ was already 8 months old and on formula when the outpatient pediatric dietitian was first consulted. He was on a reduced lactose, partially hydrolyzed protein formula, which often works well in cases of mild GI discomfort and stooling difficulties. However, PJ had had a significant surgery and a prolonged course (almost 2 months) of suboptimal formula tolerance, and his buttocks were raw and excoriated from his frequent explosive diarrhea. In this particular instance, rather than experimenting with other more semielemental formulas, a change directly to a free amino acid formula seemed to be the wisest choice, as the protein, fat, and carbohydrate are all broken down into its simplest components, thus making it much easier for an infant or child to digest and absorb.
Elevated cost and taste are often prohibitive factors in successfully using amino-acid-based formulas. In this particular case, PJ actually loved the taste of his formula (the toddler formulas are available in a variety of flavors), and he luckily qualified for the Women Infant and Children Program, so his formula cost was covered. One challenge when using these formulas is preparation technique (i.e., recipe they are using to make formula) as they are only available in powder form and commonly have a different mixing procedure than a more standard formula. This RD highly recommends that formula preparation recipe should be inquired about at every clinic visit, as even tiny adjustments (made on their own or by their local caregiver) or mistakes in preparation can lead to undernutrition/overnutrition, affect GI tolerance, and in some extreme cases, even impact fluid and electrolyte status.
Complications of Eosinophilic Enteritis
Although stool-related complications are not uncommon after surgical intervention for Hirschsprung’s disease, a confounding factor in this particular case was that PJ had evidence of eosinophils in the colon and rectum as early as the seventh day of life. This is rather unusual, and per literature review, he is the youngest and only patient reported with EMG concurrently with HD (Phillips et al., 2013). Myenteric ganglionitis is an inflammatory neuronal enteropathy that leads to intestinal pseudo-obstruction. PJ’s biopsies of the rectum showed aganglionosis indicating HD. The colonic biopsies showed eosinophilic infiltration of the myenteric plexus and eosinophil degranulation within the myenteric plexus. Both conditions can cause anorexia, bowel management issues, poor weight gain, vomiting, and intestinal obstruction (Behjati et al., 2009). Whereas HD is managed only by surgery, EMG is typically managed by dietary modification and use of immunosuppression/anti-inflammatory treatments (Schappi, Smith, Milla, & Lindley, 2003). In this particular case, diet alone appeared to improve the eosinophilia. This is contradictory to other reported cases in older patients in a retrospective study that reviewed similar cases (aged 1 month–15 years) in that they needed a combination of diet intervention and medication for optimal control (Schappi et al., 2003).
Eosinophils are white blood cells—they are found in the bone marrow (where they are formed) and in the lamina propria (moist layers of thin, loose connective tissue that line the mucous membranes of the GI tract) where they play a protective role against parasites (Registry for Eosinophilic Gastrointestinal Disorders, 2011). Eosinophilic disorders occur when these cells are found in greater-than-normal concentrations in various areas of the body. When the body wants to attack a substance (such as infection, a food allergen, something in the environment toxic to the body), the cells move into the affected area and release toxins. In doing so, they cause damage to surrounding tissues because of the inflammatory response. Over time, the inflammation to the surrounding tissue can be severe, and the symptoms of poor eating/anorexia, vomiting, and constipation occur. It is not uncommon to have young patients describe “food getting stuck” or “needles in my stomach when I eat” when they begin to grow and are able to express themselves during clinic interviews.
Although reported cases and documentation of treatment for eosinophilic esophagitis (EoE) are rapidly increasing, one limiting factor in this particular case is that the pediatric “norms” for infants and children with eosinophilic colitis or enteritis are not well defined (Bates, 2012). Of interest, studies suggest that clinical symptoms seen are related to the location of eosinophil tissue involvement. Mucosal eosinophils display diarrhea, vomiting, or malabsorption; muscular involvement is often associated with an obstructive picture, and eosinophils with serosal involvement often present with ascites (Ngo, Furla, & Burks, 2004). In this particular case, PJ’s biopsies showed eosinophils in the myenteric plexus and surrounding smooth muscle of transition zone (area where normal bowel becomes aganglionic), colon, and rectum.
There is a significant link between eosinophilic disorders and food allergy. It is well documented in cases of EoE that use of an elemental diet (amino acid based/nonallergenic diet) can be used in conjunction and, at times, even in place of inhaled steroids with excellent clinical outcomes. The most commonly allergenic foods that are often eliminated in these disorders are milk, soy, wheat, egg, peanut, and tree nuts. Nutritional treatments for EoE typically involve either consuming an entirely elemental diet (consisting of amino-acid-based formula either by mouth, via gastrostomy tube, or a combination of both), a six-food elimination diet, or a more modified or tailored diet excluding foods based on symptoms and endoscopy findings. Retrospective chart reviews indicate that elemental diets have the best outcome, with 95% resolution of symptoms, followed by the elimination diet (75%; Bhatia & Greer, 2008).
The role of food allergy in other types of eosinophilic disorders does not have clear-cut guidelines. However, in our case, PJ had a dramatic and rapid response to the formula change from a partially hydrolyzed formula (milk proteins are present but have been broken down) to a completely dairy-free, amino acid formula. He also showed repeated clinical symptoms of pain, anorexia, and loose stools when milk and, later, soy were introduced into his diet. It is also worth noting that, upon changing to an amino-acid-based formula, his follow-up biopsies indicated no further evidence of eosinophils. Although soy is sometimes used as a replacement for milk in diets, there is a high reported frequency of sensitivity to both cow’s milk and soy antigens in infants with documented cow milk protein enteropathy. Although the literature is mixed on the position of soy products, the general consensus is that soy-based formulas are not recommended (especially before 6 months old) and use of a hydrolyzed protein formula should be used instead (Wu, Francoisi, Rothenberg, & Hommel, 2012).
PJ’s mother attempted on two occasions to challenge him with milk-based products, and he consistently tolerated both trials poorly and returned to a milk-free diet. Whenever an infant or child is eliminating certain food groups to manage GI symptoms, the pediatric dietitian must work diligently with the family to prevent deficiencies developing over time, and appropriate substitutes are made to replace these nutrients (see Table 2). In some cases, keeping a diet journal including food intake and any concurrent GI symptoms can really help the RD and family pinpoint which types of foods may be causing the issue. It can also identify any areas in the diet that may be deficient, so focus can be placed on how to replace these nutrients. In PJ’s case, he really enjoyed the amino acid formula, and as this is considered a complete source of nutrition, there was less concern for nutrient deficiencies. One study found a significantly higher level of behavioral feeding problems in children with eosinophilic gastrointestinal disorders (Hyman, 2009). PJ has not shown any overt behavioral feeding-related issues, which, again, is unusual considering he has contended with both milk and soy sensitivities coupled with a chronic constipation picture as complication of his HD.
It is estimated that approximately 5%–10% of children with previous surgery for HD will have long-term issues with constipation, incontinence, and abdominal pain (Kessmann, 2006). It is also common for children who have had corrective surgery for this condition to need unpleasant, sometimes painful, procedures, such as rectal dilations, enemas, and GI cleanouts. Any and all of these can contribute to a toddler or child to “hold” or resist using the bathroom, prolong toilet training, and have accidents. This can contribute to family stress, delayed toilet training, and embarrassment for the child.
Nutritional interventions such as counseling on adequate amounts of fluid and fiber in the diet can be beneficial for parents to review regularly, as this will help encourage softer, formed stools. These diet interventions are often used in conjunction with a stool softener. In PJ’s case, the pediatric GI team was watching this closely at each consecutive follow-up clinic visit and continued to troubleshoot regularly with PJ and his parents. He continues to have some incontinence and constipation at the age of 3 years, requiring occasional trips to the emergency department and inpatient GI cleanouts. This RD has counseled his mother on higher fiber foods, along with the need for adequate fluid intake to prevent further hard stools, and handouts have been provided for home use.
Because different fibers have different effects in the body, emphasis is placed on using a combination of dietary fiber in the diet. These are composed of soluble fibers and insoluble fibers. Soluble fiber (fibers that can dissolve in water) can help slow digestion, reduce low-density lipoprotein cholesterol, and have prebiotic benefits for the body. Examples of soluble fiber include legumes, fruits, and vegetables (although many are a combination of both in that the skin is a source of insoluble fiber whereas the fruit itself is a soluble fiber source). In addition, flaxseeds are a nice source of soluble fiber and can be added to foods relatively easily. Insoluble fiber helps move water through the intestines, increases fecal bulk, and prevents constipation. Examples of insoluble fiber in the diet are whole grains and popcorn. In addition, there has been an explosion of “functional fibers” in the food industry (made up of starches, pectins, and gums), which are added to foods that are not normally thought to be a good fiber source in the diet. Examples of this might be certain sports drinks and refined pastas and cereals (Kranz, Brauchla, Slavin, & Miller, 2012).
PJ’s mother made a very common mistake after one nutrition visit in that she quickly and substantially increased foods containing higher fiber in his diet without subsequent increase in fluid intake—this unfortunately led to an exacerbation of his constipation but was quickly fixed at the next follow-up appointment a month later after obtaining a detailed diet history. One challenge of providing adequate daily fiber in the diet for toddlers is that many foods containing higher amounts of fiber tend to be less palatable or harder to chew and swallow (see Table 3 showing examples of toddler-friendly higher fiber foods). Certain goals routinely reviewed are to use label reading as a guideline when making food choices. For example, shopping for cereals with 3–5 grams of fiber per serving and breads with at least 3 grams per serving are two easy ways to obtain a regular source of fiber in a young child’s diet.
An additional nutrition challenge is that there is not a good consensus on exactly how much fiber a young toddler and child need per day. Although studies are mixed with no true consistency in recommendations, the Dietary Reference Intake recommends 19 grams of fiber per day for children aged 1–3 years and 25 grams per day for children aged 4–8 years (Kranz et al., 2012). This recommendation also falls into place with the American Heart Association consensus statements. As a quick reference point, they also cite 14 grams per 1000 calories consumed in toddlers and young children, which in generally lines up with the Dietary Reference Intake guidelines. Many parents will often ask the author about the “age plus five” rule for fiber—this was established by the Institute for Cancer Prevention in 1994 and, in general, is thought to be outdated and too low. In the case of a child with a predisposition to constipation (as in PJ’s case), this recommendation would not be high enough to best treat his constipation. Most children (and adults) do not meet daily fiber intake recommendations and need ongoing counseling. This becomes paramount in the instance where there is a higher risk of constipation, which is evident in this particular case.
This case shows how collaboration between the pediatric dietitian and the pediatric surgical team can lead to better nutritional outcomes including optimal growth, improved formula tolerance, and decreased GI-related complications after surgery. It also reinforces how long-term follow-up is critical from both a nutrition and surgical standpoint, to address the long-term nutrition issues that can ensue from surgical intervention of HD in infancy. This particular case is especially interesting as the patient is the youngest documented case found in the literature with a case of EMG occurring with HD.