Chronic Intestinal Pseudo-Obstruction

Clinical Presentation

The majority of children with CIPO will develop symptoms at or shortly after birth, with 50% presenting in the first month of life and 65% to 76% developing symptoms during the first year of life. ^, In the Japanese nationwide study, 56% had onset of symptoms in the neonatal period. Symptoms vary based on age of onset.

Congenital CIPO, defined as symptoms of pseudo-obstruction at birth that persist for over 2 months, is associated with increased morbidity and mortality when compared with CIPO that presents later in life. ^, A significant proportion of infants with congenital CIPO will have signs of hollow viscera disease during prenatal evaluation (17%), most often with the findings of megacystis, polyhydramnios, or dilation of the upper urinary tract. CIPO occurs more frequently in preterm births, although preterm delivery may be a consequence of fetal distress related to CIPO.

In the neonatal form, CIPO presents with abdominal distention and bilious emesis. This diagnosis should be suspected once Hirschsprung disease and intestinal malrotation have been ruled out, as well as in those patients with a prenatal diagnosis of megacystis or bladder dysmotility. Patients with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) present with abdominal distention due to an obstructed urinary system; symptoms of intestinal obstruction follow days to months later.

In infants or children, CIPO typically presents with episodes of exacerbation separated by periods of relative improvement. During these episodes of worsening, children often develop clinical symptoms similar to those of bowel obstruction ( Table 44.1 ). The most common symptoms in children are abdominal distension (85% to 98%), vomiting (55% to 91%), and constipation (50% to 77%). Children with CIPO will often have abdominal pain (58% to 70%) and poor weight gain (27% to 72%). Diarrhea can develop in a significant proportion of patients (25% to 31%) and may be secondary to intestinal dysmotility or subsequent small bowel bacterial overgrowth. Small bowel bacterial overgrowth is a relatively common complication of CIPO and can lead to mucosal inflammation and further impairment of GI motility. ^{, ,}

Episodes of exacerbation can occur without apparent provocation or may be associated with stress, anesthesia, infection, or poor nutritional status. The intermittent nature of CIPO and the apparent self-resolution of acute episodes contribute to the challenge of making an accurate and timely diagnosis. It is difficult to predict the long-term course in a child with CIPO in part because of the heterogeneity of underlying disease processes that can lead to CIPO.

Pathophysiology

Physiologic GI motility relies on the coordinated interaction of a number of factors, including the enteric nervous system, intestinal smooth muscle, and the interstitial cells of Cajal (ICCs). The dysfunction of any of these factors can result in GI dysmotility and, if sufficiently severe, CIPO. CIPO is therefore categorized into neuropathic, myopathic, and mesenchymopathic types based on the nature of the responsible defect.

Neuropathic type CIPO is the result of neurologic dysfunction, primarily due to an abnormality of the enteric nervous system. This encompasses a multitude of mechanisms, and histologic examination of affected bowel in patients with neuropathic-type CIPO can show partial or total aganglionosis, ganglion damage or degeneration, myenteric plexus hyperplasia, or myenteric infiltration by inflammatory cells, typically lymphocytes or eosinophils. ^, Neuropathic-type CIPO in children differs from CIPO in adults, in that the defect is more often secondary to maturational arrest rather than plexus degeneration.

Myopathic type CIPO is the result of a defect in the intestinal smooth muscle. Patients with myopathic type CIPO have been found to have absent smooth muscle, an extra muscle layer, an abnormal smooth muscle pattern, or contractile protein anomalies. Histologic evaluation of affected bowel can also show fibrosis and vacuolization of the muscular layers. ^,

Mesenchymopathic-type CIPO is the result of dysfunction of the ICCs and is the least common of the three types described. The ICCs both facilitate communication between the enteric nervous system and intestinal smooth muscle and act as pacemaker cells for the intestinal smooth muscle in stimulating and propagating peristalsis. The complete absence of ICCs in association with CIPO has been previously described in adults and more recently in children. Both the abnormal distribution and delayed maturation of the ICCs have also been found in children with CIPO.

CIPO can be a primary or secondary process. Primary CIPO is typically sporadic, but genetic influences have been described, with inheritance patterns corresponding with autosomal dominant, autosomal recessive, and X-linked modes of inheritance. Primary CIPO is more common in children than in adults, which helps to explain the predominance of pediatric CIPO presenting very early in life. CIPO can also be secondary to a wide variety of conditions ( Box 44.1 ). It is important to recognize that a congenital presentation does not preclude secondary CIPO, as in the case of CIPO secondary to a prenatal insult. CIPO has been associated with prenatal exposure to alcohol, suggesting that alcohol may affect not only the developing central nervous system but also the enteric nervous system. Some cases of secondary CIPO may improve with treatment of the primary disorder, as is the case with eosinophilic disease or hypothyroidism, or with removal of the inciting factor, such as cases secondary to narcotic use. ^,

From an infectious diseases standpoint, there has been increasing interest in the role of herpesviruses, specifically cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes zoster, and polyomaviruses such as John Cunningham virus (JC virus). JC virus has been found to be active in the myenteric plexus of adults with CIPO significantly more often when compared with controls. The relationship between CIPO and mitochondrial disease has also been well documented. In a series of patients with CIPO that included both children and adults, 20% were found to have evidence of a mitochondrial disorder. Although patients with CIPO secondary to a mitochondrial disorder will typically have multiorgan involvement, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an exception in that it often presents primarily with GI symptoms. ^, MNGIE is also associated with external ophthalmoplegia, deafness, peripheral neuropathy, and diffuse muscle weakness. Almost all patients have evidence of leukoencephalopathy on brain magnetic resonance imaging (MRI).