Chronic intestinal pseudo-obstruction (CIPO) is defined as repetitive or continuous symptoms and signs of bowel obstruction in the absence of a fixed, lumen-occluding lesion. CIPO is a result of the inability of the gastrointestinal tract to move contents through an unobstructed lumen, and therefore is the most severe form of gastrointestinal motility disorder and can lead to significant morbidity and mortality. Radiographic documentation of dilated bowel with air-fluid levels may be seen, depending on the severity and type of CIPO and patient age. Although much progress has been made since the initial description of pseudo-obstruction in 1958, CIPO remains a diagnosis that is difficult to diagnose and can be frustrating to manage. The diagnosis of CIPO is applied to a number of heterogeneous disorders that are unified by similarities in their clinical presentation, evaluation, and management. These disorders are broadly categorized by their mechanism into neuropathic, myopathic, and mesenchymopathic types. The prevalence of CIPO in children is uncertain, with a past estimate that approximately 100 infants are born each year in the United States with congenital pseudo-obstruction. Some studies have shown a male predominance among both children and adults with CIPO, although this has not been a consistent finding.
Clinical Presentation
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 gastrointestinal motility.
| Abdominal distension | 85% to 98% |
| Vomiting | 55% to 91% |
| Constipation | 50% to 77% |
| Abdominal pain | 58% to 70% |
| Poor weight gain | 27% to 72% |
| Diarrhea | 25% to 31% |
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.
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. 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.
Urinary tract involvement is seen in a significant proportion of children with CIPO, most often manifesting as urinary retention or recurrent urinary tract infections. Urodynamic studies may show a large atonic bladder without a distal structural obstruction. Urinary tract involvement appears to occur more commonly in myopathic type CIPO but can also occur with neuropathic type CIPO. The presence of microcolon in addition to intestinal dysmotility and urinary tract involvement suggests megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS).
Intestinal malrotation is also associated with pediatric CIPO and is found in 25% to 28% of cases compared to 10% of the general population. These patients generally do not experience resolution of their symptoms after surgical intervention. The relationship between intestinal malrotation and CIPO is unclear, but it has been postulated that impaired motility of the fetal gastrointestinal tract may lead to impaired intestinal rotation and return to the abdominal cavity during gastrointestinal tract development.
Pathophysiology
Physiologic gastrointestinal 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 gastrointestinal 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 not only affect 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.
Autoimmune
Autoimmune myositis
Autoimmune ganglionitis
Scleroderma
Endocrine
Diabetes mellitus
Hypoparathyroidism
Hypothyroidism
Gastrointestinal
Celiac disease
Eosinophilic gastroenteritis
Inflammatory bowel disease
Hematology/Oncology
Multiple myeloma
Paraneoplastic syndromes
Pheochromocytoma
Sickle cell disease
Infection
Chagas disease
Cytomegalovirus
Epstein-Barr virus
Herpes zoster
JC virus
Kawasaki disease
Postviral neuropathy
Medications and Toxins
Chemotherapy
Cyclopentolate and phenylephrine eye drops
Diltiazem and nifedipine
Fetal alcohol syndrome
Jellyfish envenomation
Opioid medications
Postanesthesia
Radiation injury
Mitochondrial Disorders
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
Musculoskeletal Disorders
Ehlers-Danlos syndrome
Myotonic dystrophy
Duchenne muscular dystrophy
Rheumatology
Amyloidosis
Dermatomyositis
Polymyositis
Systemic lupus erythematous
From an infectious diseases standpoint, there has been increasing interest in the role of herpesviruses, specifically cytomegalovirus, Epstein-Barr virus, and herpes zoster, and polyomaviruses such as JC virus (John Cunningham virus). JC virus has been found to be active in the myenteric plexus of adults with CIPO significantly more often when compared to controls. The relationship between CIPO and mitochondrial disease has also been well documented. In a series of CIPO patients 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 gastrointestinal symptoms.
Diagnosis and Evaluation
Making a timely and accurate diagnosis of CIPO can be a challenge, and a structured approach is necessary. The diagnosis of CIPO is made based on clinical presentation with the support of radiographic and manometric studies. Transit time measurement and histologic evaluation of affected bowel may be useful as well. Of particular importance is to rule out mechanical bowel obstruction. It is critical to recognize that volvulus has been described in patients with CIPO and can be difficult to distinguish from an episode of exacerbation of CIPO. Certain clinical features should raise the practitioner’s clinical suspicion for CIPO. A history of chronic symptoms and weight loss, particularly if prior exploratory laparotomies have not demonstrated mechanical obstruction, would suggest CIPO rather than a true mechanical obstruction. Myopathic type CIPO can often present with concurrent urinary symptoms, such as urinary retention or a history of recurrent urinary tract infections. A family history of visceral myopathies or neuropathies should also alert the practitioner to the possibility of CIPO.
The utility of laboratory testing in the diagnosis of CIPO is limited, but can be important in directing acute management and evaluation for a primary process responsible for secondary CIPO. Recommended laboratory tests include a complete blood count, electrolytes, erythrocyte sedimentation rate (ESR), urinalysis, thyroid studies, screening for celiac disease, and nutritional assessment. Sweat test and screening for metabolic disorders, mitochondrial disorders, paraneoplastic syndromes, and infection (Epstein-Barr virus [EBV], cytomegalovirus [CMV], herpes simplex virus [HSV], and rotavirus) may be indicated as well.
Radiographic evaluation is of particular importance in CIPO. Abdominal radiographs will often show gaseous distension and air-fluid levels suggestive of an obstructive process and can remain abnormal even during asymptomatic periods between episodes of exacerbation ( Figure 44-1 ). However, some cases of CIPO may only have intermittently dilated bowel and therefore normal radiographs do not rule out the diagnosis of CIPO. The role of computed tomography (CT) in the evaluation of CIPO has not been well defined, and expected findings would be similar to those seen on radiography, namely distended bowel loops and air-fluid levels. A recent study suggests that cine–magnetic resonance imaging (MRI) of the gastrointestinal tract, which allows for dynamic evaluation of peristalsis, shows an increased luminal diameter and decreased contraction ratio in adult patients with CIPO when compared to patients with irritable bowel syndrome (IBS) and healthy controls and may be a promising modality in the evaluation of CIPO.
Contrast studies of the gastrointestinal tract are important for excluding mechanical bowel obstruction. Findings of an upper gastrointestinal series with small bowel follow-through in a child with CIPO will vary depending on the location and extent that is affected, but generally will show dilated bowel proximally with very slow transit through a featureless intestine. Water-soluble contrast enema has been shown to be effective for differentiating between an acute episode of CIPO and colonic volvulus. Water-soluble contrast is recommended for all contrast studies in CIPO as the severely impaired motility of CIPO can predispose to formation of barium concretions. Contrast may also be diluted by luminal fluid in patients with significant dilation and stasis.
After the diagnosis of CIPO has been established, manometry can be useful for identifying affected segments of the gastrointestinal tract, assessing the severity of dysfunction, establishing prognosis, and guiding management ( Figure 44-2 ). Manometry studies are ideally performed during periods of symptomatic improvement when the bowel is less dilated. Myopathic type CIPO generally shows low amplitudes with preservation of normal spatial and temporal patterns. In neuropathic type CIPO, the amplitude of contractions may be low, normal, or elevated, but the pattern is typically disorganized and nonperistaltic. Prolonged contractions that are nonpropagating in the postprandial phase suggest mechanical bowel obstruction and should lead to further evaluation for true obstruction.
