Chronic intestinal pseudo-obstruction is a rare disorder that affects the motility of the gastrointestinal tract. It results in acute or subacute intestinal obstruction symptoms in the absence of mechanical lesion. It can lead to intestinal failure in children with significant strain on nutrition, growth, and development. There is no universally agreed protocol for management of chronic intestinal pseudo-obstruction in children, and there is wide variation in clinical practice.
An acetylcholinesterase inhibitor (ACI) can stimulate gastrointestinal (GI) motility by prolonging the action of acetylcholine (an excitatory neurotransmitter) in the gut. A small number of researchers have shown some effect with pyridostigmine in adult patients with chronic intestinal pseudo-obstruction (CIPO). In this case, a child with CIPO was treated successfully with pyridostigmine with sustained clinical response. To the best of our knowledge, this is the first report of using pyridostigmine in a child with CIPO.
A 9-year-old girl with a history of congenital myotonic dystrophy (MD) and learning difficulties presented with an acute onset of progressive abdominal distention, colicky abdominal pain, constipation, and vomiting for the fifth time in 6 months. All presentations were identical each and every time. She had a long-term history of constipation and intermittent abdominal distension since the age of 3 years, and she was also significantly delayed in development of continence. She used different types of laxatives, including polyethylene glycol, lactulose, senna, sodium picosulfate, and docusate sodium, with no definitive effect. All medication doses were monitored and adjusted appropriate to her age and weight. She was tried initially on a single agent laxative (polyethylene glycol) but was mostly on a combination of osmotic and stimulant laxatives through most of her life. Radiologic images during the episodes showed distended bowel loops throughout the abdomen (Fig 1). All episodes were treated as intestinal obstruction by withholding enteral feed, intravenous fluids, and gastric decompression. Because of the progressive course of the distension and pain, she underwent 2 exploratory laparotomies. Possible adhesion obstruction was noted in the first operation; the surgeon described a collapsed loop of small bowel but no dilatation surrounding the area and no rings of adhesion around the bowel. No mechanical cause was found in the second operation. The remaining episodes were treated conservatively and were resolved in ∼7 days. A water-soluble contrast study revealed dilated bowel but no evidence of contrast holdup or obstruction. She was referred to our institution with the diagnosis of intestinal pseudo-obstruction.
She was admitted to our ward with another episode of abdominal distension, nausea, and constipation. The mean average of nasogastric free drainage was 1100 mL per day during the initial phase, and the mean average of abdominal girth was 77 cm. She was started on enteral pyridostigmine at a dose of 0.5 mg/kg twice per day and gradually increased to 1 mg/kg twice per day while monitoring her heart rate. She had good clinical response to passing spontaneous bowel motions (average of 2 spontaneous bowel motions per day), reduction in abdominal distension as measured by serial abdominal girth (mean average was 70 cm), reduction of the volume of gastric drainage, and she was able to tolerate normal enteral intake (Fig 2). An abdominal radiograph revealed improvement in bowel distension (Fig 3). Because of her learning difficulties and long-term need for a nasogastric tube to supplement fluid intake, she underwent a gastrostomy insertion. She was discharged from the hospital and remained well, maintaining normal eating and gaining weight for a period of 7 months. She was readmitted with a milder episode of abdominal distension and vomiting, which was resolved in 48 hours (significantly shorter than previous episodes). The dose of pyridostigmine was increased to 1.5 mg/kg twice per day while closely monitoring her heart rate. She remains under close follow-up for 12 months with good clinical response.
CIPO is a rare condition affecting mainly the small intestine and the colon, resulting in obstructive symptoms in the absence of mechanical lesion.1 It is characterized by an impairment of the normal GI propulsion system and is an important cause of intestinal failure for both children (15%) and adults (20%).2 Pediatric cases are particularly concerning because CIPO restricts the ability to maintain growth and nutrition.3 The incidence and prevalence of CIPO remains largely unknown. It is estimated that 100 infants are born with CIPO annually in the United States.1 The authors of a more recent study in Japan, however, estimated a prevalence rate of 1 in 270 000 in children less than the age of 15, with equal sex incidences.4
The vast majority of CIPO cases are sporadic and are classified as primary or secondary. Primary cases are subcategorized as 1 of 3 subcategories, neuropathic being the most common, followed by myopathies and mesenchymopathies.1,2 The majority of pediatric CIPO cases are idiopathic, with 65% to 80% of children becoming symptomatic by 12 months of age, whereas 50% of adult cases are secondary to the underlying disease.1 The common feature between the different pathologic causes of CIPO is that there is impaired GI peristalsis that typically manifests and presents with obstructive signs and symptoms.
Presentation may be acute or progressive, with symptoms suggesting partial or complete mechanical obstruction without the presence of obstructing lesions. Children have been reported to more commonly present with urological involvement such as urinary retention and recurring urinary tract infections in addition to abdominal pain and distention.5,6 Our patient did, in fact, have a history of intermittent constipation from the age of 3 and had a significantly delayed development of continence.
The diagnosis of CIPO is usually clinical.1,2 Investigations are usually performed to rule out mechanical obstruction via radiologic images. Our patient had serial plain abdominal radiographs and a water-soluble contrast study that confirmed the patency of the intestine, although computed tomography or MRI enterography is more accurate in detecting mechanical obstruction and intestinal adhesions. Investigations are also usually performed to identify an underlying pathology leading to CIPO. Antroduodenal manometry can be helpful in defining the pathophysiological process involved (neuropathy, myopathy, or mixed features). However, antroduodenal manometry has low diagnostic yield and does not influence management.1 Because of her underlying learning difficulties, our patient was not able to tolerate manometry. Full thickness biopsies may provide diagnostic and prognostic answers. Histology can describe the interstitial cells of Cajal network and the neuromuscular structures.1,2 In this case, unfortunately, no biopsies were taken during the previous surgeries, and because she responded to treatment with pyridostigmine, it was not necessary to subject her to another invasive procedure, considering that the available therapeutic options for management of CIPO are not that effective and are mostly directed toward symptom relief, provision of adequate nutrition, promoting intestinal motility, and avoidance of unnecessary surgery.
In our case, the patient was also diagnosed with congenital MD, an autosomal dominant, multisystemic disease affecting both striated and smooth muscles. It is characterized by myotonic muscular dystrophy, cardiac conduction defects, cataracts, and endocrine disorders.7 Clinically, the predominant feature of MD is progressive muscle degeneration that results in weakness, wasting, and myotonia. Similar to CIPO, the diagnosis of MD is often delayed with as much as 5 years elapsing between presentation and diagnosis.8
GI involvement in MD is common. Researchers highlight that up to 40% of children and young adults can experience GI symptoms, which include pain, bloating, altered bowel habit, and constipation.9 Furthermore, Rönnblom et al10 conducted a study in 2002 to monitor gastric emptying in 10 patients with MD; in this study, they suggested that MD is associated with reduced gastric motility. However, because of a lack of high-quality studies, it is still up for debate whether MD causes CIPO via damage to the enteric nervous system, smooth muscle, or secondary endocrine changes.11,12
Medical intervention should be based on high-quality evidence; however, the scientific literature on MD and CIPO is limited. Case reports appear to be the main source of information, such as those by Brunner et al,12 Bruinenberg et al,13 and Glaser et al.11 The interventions reported to have been used include prokinetics and are surgical in nature. Most recently, in 2015, Glaser et al11 reported a similar pediatric case of a 10-year-old girl with MD who also presented repetitively with fecal impaction and CIPO. After the patient was diagnosed with CIPO, persistent symptoms resulted in a total colectomy procedure being conducted to allow the patient to be symptom-free for 17 months. Surgery for a child is an invasive and traumatic experience and should be reserved as the last option. There is also some doubt as to whether surgery is needed. Yoshida et al14 conducted hemicolectomies in MD patients and histologically found normal smooth muscle but marked neurologic insults. The lack of conclusive evidence for surgical procedures that are irreversible demotes the intervention to be the last therapeutic option in our view.
Pyridostigmine is an ACI that promotes the action of acetylcholine, a chief excitatory neurotransmitter in the GI tract. Evidence for supporting the use of ACIs in GI dysmotility includes multiple small trials with neostigmine15 and a recent meta-analysis by Valle and Godoy,16 all revealing positive results.17,–21 Furthermore, in a study by O’Dea et al,22 7 adult patients with pseudo-obstruction were treated successfully with pyridostigmine, with marked improvement in symptoms and a decrease in the use of laxatives for constipation, further supporting the notion that ACI therapy for CIPO is an effective medical approach, as was the case in our patient. An important limitation of all the evidence mentioned is that a majority of the reports were written by researchers studying adults, not children.
We report a case of a child with MD and CIPO who had sustained clinical response with the use of pyridostigmine, an ACI. To the best of our knowledge, this is the first report of the use of pyridostigmine in children with CIPO. There remains an urgent need for a properly designed study so that more evidence regarding the use of pyridostigmine in children with CIPO can be provided.
Mr Choudhury and Mr Rahyead collected the clinical information and drafted the initial manuscript; Dr Kammermeier reviewed and revised the manuscript; Dr Mutalib identified the case, supervised data collection, and reviewed the manuscript; and all authors approved the final manuscript as submitted.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.