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Lakshmana Das Narla, M.D.
    Department of Radiology
    Medical College of Virginia
    of Virginia Commonwealth University
    Richmond, Virginia


Elizabeth A. Hingsbergen, M.D.
    Department of Radiology
    Medical College of Virginia
    of Virginia Commonwealth University
    Richmond, Virginia

Charles E. Bagwell, M.D.
    Department of Pediatric Surgery
    Medical College of Virginia
    of Virginia Commonwealth University
    Richmond, Virginia

    Pneumatosis intestinalis was described in 1946 by Lerner and Gazin and defined as "the presence of gas in an abnormal location in the body".   Pneumatosis is an imaging sign and not a diagnosis.  More than fifty causative factors have been implicated, varying from life threatening necrotizing enterocolitis, ischemia, and infarction of bowel to non-emergent medical and iatrogenic causes (Table 1)

    Pneumatosis has been divided into two groups: primary (idiopathic) and secondary.  In the past, pyloric obstruction or ulcer disease was one of the most frequent causes of pneumatosis.  Now, pneumatosis is more likely to be encountered in patients undergoing transplantation or chemotherapy.  Pneumatosis can be delineated on abdominal radiographs, barium enema, computed tomography (CT) with wide windows, magnetic resonance imaging (MRI), and ultrasound (US) including endosonograms [Figures 1,2,3,4];    Intramural intestinal gas can be generalized or organ related.  In the stomach it is often referred to as emphysematous gastritis.  The intramural gas may be cystic/bubbly (submucosal), or curvilinear/linear (subserosal) [Figures 5,6,7].   Pneumoperitoneum and pneumoretroperitoneum can be present regardless of the cause.   Free intraperitoneal air develops in pneumatosis whenever one of the subserosal collections of gas ruptures [Figures 8,9].

    Typically the gas collections are found in the subserosa, less commonly in the submucosa, and rarely in the muscularis layer, and vary in size from a few millimeters to greater than a centimeter.  They are found more often along the mesenteric side of the bowel, but can be seen along the antimesenteric side and even within the mesentery itself. 

Table I
PATHOLOGICAL CLASSIFICATION OF
PNEUMATOSIS INTESTINALIS

A.   Bowel Necrosis
    Necrotizing enterocolitis - NEC
    Ischemia and Infarction
    Neutropenic colitis
    Sepsis
    Emphysematous gastritis
    Caustic ingestion

B.   Mucosal disruption
   
Pyloric obstruction
    Bowel obstruction
    Blunt abdominal trauma
    Trauma of child abuse
    Hirschsprung disease
    Crohn's disease
    Ulcerative colitis

C.   Increased mucosal permeability
   
Immunotherapy
        - graft versus host disease
        - organ transplantation
        - bone marrow transplantation
    AIDS enterocolitides
    Steroid therapy
    Chemotherapy
    Collagen vascular disease

D.   Pulmonary disease
   
Asthma
    Chronic pulmonary disease
    Cystic fibrosis
    Chest trauma

Source: Modified from Bert Lincoln Pear


Etiology and Theories of Pneumatosis

Bacterial Theory:

    Clinical and experimental evidence confirms that gas produced in pneumatosis is of bacterial origin.  Analysis of the gas within the cysts indicates that it consists of approximately 50% hydrogen, compared with 14% hydrogen is normal intestinal gas, favoring a bacterial origin of the gas.  A bacterial origin of pneumatosis would also account for the inflammatory reaction evident around the cysts.  Hyperbaric oxygen has been used to treat both pneumatosis and clostridium infections.  In some cases, pneumatosis does respond to antibiotic treatment. 

Mechanical Theory:

    Gas enters the bowel wall because of direct trauma or increased pressure.  Mechanical disruption of the bowel wall is the main cause of pneumatosis in cases of trauma, surgery or endoscopy, and is a predisposing cause in pneumatosis associated with obstruction.

Mucosal Damage Theory:

    Mucosal disruption is the primary causative factor in virtually all cases of pneumatosis so that bacteria or gas become forced into the bowel wall.  Mucosal disruption is the primary causative factor of pneumatosis associated with inflammation or ischemia.  In Crohn's disease, use of steroids depletes Peyer patches resulting in pneumatosis.

Pulmonary Disease Theory:

    Pulmonary causes of pneumatosis intestinalis include chronic obstructive pulmonary disease, asthma and cystic fibrosis.  It can also occur with barotrauma and after chest tube placement.

Pneumatosis Intestinalis Secondary to Necrotizing Enterocolitis:

    Necrotizing enterocolitis (NEC) is the most common, and at times fatal, acquired GI emergency in the neonatal intensive care unit.  Ten percent of infants weighing less than 1500 grams have definite NEC and another 17% have possible NEC. 
    A staging system developed by Bell recognizes three stages:
        Stage I,       early or suspected NEC;
        Stage II,      definite NEC; and
        Stage III,     advanced disease. 
    The exact etiology of NEC is unknown; ischemia, infection, and hyperosmolar feeds contribute to the development of NEC.   Unfed babies seldom develop NEC.  Occasionally there are epidemic outbreaks of NEC in newborn nurseries, which suggests an infectious etiology.  Symptoms in the form of abdominal distention, feeding intolerance, vomiting, blood in the stool, diarrhea, lethargy, instability of temperature and blood pressure, and apnea are usually seen in the first week of life.  In advanced disease, the signs may include erythema of the body wall, and palpable distended bowel loops [Figure 10].  The mortality of NEC is about 30%, but is higher in very low birth weight infants.  Though NEC is more common in premature infants, it may occur in full term infants with risk factors including hypoxia, hypoglycemia, polycythemia, respiratory distress syndrome, congenital heart disease [Figure 11], cardiac surgery [Figure 12], repair of gastroschisis, [Figure 13] and intestinal atresia.  Babies born to mothers who abuse cocaine also have a higher incidence of NEC [Figure 14]
    In NEC, inflammation begins in the mucosa and submucosa and may extend through the full thickness of the bowel wall.  Involvement may be diffuse but is usually patchy [Figures 15 A & B].  The distal ileum and right colon are involved far more frequently than any other site though any part of the intestine may be affected.
    Plain films are routinely and commonly used for the diagnosis and follow-up of patients with NEC.  The most commonly detected abnormality is diffuse gaseous distention of the intestine, a non-specific finding.   A persistent area of dilated bowel may indicate focal involvement of bowel with NEC.  Pneumatosis in the form of submucosal or subserosal air is classic for NEC.  The bubbly submucosal morphology of pneumatosis is easily confused with stool or meconium in a normal colon.  In difficult cases follow-up films are helpful, as stool will usually move whereas pneumatosis may not.  At times prone views may also be helpful in distinguishing pneumatosis from stool. The medical treatment of NEC consists of bowel decompression with an NG tube, NPO, IV fluids and antibiotics. The reported incidence of portal venous gas (PVG) in NEC varies widely, and probably occurs in between 10% and 30% of patients. PVG is not an indication for surgery.  Free intraperitoneal air is an indication for surgery, and can be detected on supine film, left lateral decubitus film or supine cross table lateral film [Figure 16].  Only one half to three quarters of patients with perforation have free air detectable even on horizontal beam films.  A patient weighing less than 1500 grams may be too unstable to go to the operating room and can be treated by percutaneous peritoneal drainage at the bedside [Figure 17].  This technique can be very successful in temporizing in the very ill neonate.  In 40% of these infants, no further therapy is needed; the other 60% of infants generally require surgery at a later date.

Complications of NEC:

    The complications of NEC are strictures, enterocyst formation, malabsorption, inflammatory polyps, and enteric fistulae.  Intestinal strictures may follow either medical or surgical management of NEC and occur in 10% to 20% of survivors.  Although NEC mostly affects the distal ileum and right colon, most strictures occur in the left colon, and most often occur in or adjacent to the splenic flexure [Figure 18].  Colonic strictures are multiple in 30% of cases.  Strictures can be treated more conservatively by balloon catheter dilatation.  In children who have had diversion ileostomy or colostomy, it is important to evaluate the distal defunctionalized bowel with contrast enema to rule out strictures before reanastomosis.

Pneumatosis Intestinalis Secondary to Viral Cardiomyopathy:

    Any patient with poor cardiac function and failure can be at risk for pneumatosis intestinalis and associated perforation.  In the first 2 days of life, development of pneumatosis should raise a red flag for hypoplastic left or right heart syndrome.
Case: A nine year old patient with history of band heterotopia, presented with acute onset of respiratory failure.  Chest x-rays [Figure 19] showed marked cardiomegaly with failure.  Echocardiogram showed poor contractility with ejection fracture of 10%.   During the PICU management of cardiac failure, she developed abdominal distension.   Abdominal films revealed extensive pneumatosis of the right colon.  Over the next week, her cardiac function improved as did the pneumatosis intestinalis.

Pneumatosis Intestinalis Secondary to Blunt Abdominal Trauma:

    Pneumatosis secondary to mucosal disruption can be caused by ulceration, erosions or trauma (blunt abdominal trauma including non-accidental trauma - child abuse). 

Case:  A 5 year old cerebral palsy patient was involved in a motor vehicle accident.   Initially he was admitted for a right humerus fracture; during the hospital stay he developed extensive pneumatosis and portal venous gas [Figure 20].

Gastric Hematoma and Pneumatosis in Child Abuse:

    John Caffey in 1946 noted an association in children of subdural hematoma and long bone fractures.  In 1962, Kempe and Silverman wrote the classic article entitled "The Battered Child Syndrome".  Of child abuse and neglect fatalities, 90% are younger than five years and 40% are infants <1 year of age.  The classic metaphyseal corner fracture bucket -handle fracture of long bones has the highest specificity for child abuse.  Mortality and morbidity are from central nervous system (Shaken baby syndrome) and visceral injuries.  The spectrum of visceral injuries in child abuse include: gastric perforation, gastric intramural hematoma and pneumatosis, perforation of small bowel (with 60% occurring in jejunum distal to the ligament of Treitz, 30% in duodenum and 10% in ileum), duodenal, jejunal and colonic hematoma, pancreatitis and pancreatic pseudocyst, and liver, spleen and kidney laceration.   Adrenal hemorrhage, chylous ascites and bladder rupture are also associated with child abuse.

Case:  A 21 month old girl was brought to the emergency department unconscious and hypotensive.  Physical examination revealed multiple bruises, lacerations and human bite marks on the abdomen and back.  Radiological work up included normal chest, cranial CT and skeletal survey.  Abdominal CT showed gastric antral thickening due to intramural hematoma [Figure 21A].  Upper gastrointestinal examination showed antral hematoma and no duodenal hematoma [Figure 21B].  On the second day she had increasing abdominal tenderness and elevated white count with left shift.  Repeat abdominal CT showed gastric pneumatosis [Figure 21C], which resolved with conservative management.   The intramural hematoma may result in gastric mucosal tear, and subsequent dissection of air into the wall of the stomach is enhanced by partial or complete obstruction.  Antral hematoma and gastric pneumatosis are additional intraabdominal manifestations of child abuse.

Pneumatosis Intestinalis Secondary to Obstruction:

    Pneumatosis secondary to mucosal disruption presumably due to overdistention is seen in peptic ulcer, pyloric stenosis, annular pancreas, and more distal obstructions.  The causes for acquired small bowel obstruction in children include appendicitis, adhesions from previous surgery, intussusception, incarcerated inguinal hernia, malrotation with midgut volvulus, and Meckel's diverticulum.

Case:  A six week old infant presented with vomiting and abdominal distension.   Abdominal films [Figure 22 A&B] showed an obstructive bowel gas pattern with pneumatosis; the obstruction was secondary to incarcerated inguinal hernia.
Pneumatosis Intestinalis Secondary to Hypertrophic Pyloric Stenosis (HPS):

    In 1952, Koch described a 59 year old man with complete pyloric stenosis associated with peptic ulcer, resulting in pneumatosis of ileum.  Fifty-five percent of all cases of pneumatosis reviewed at the time were secondary to gastric or duodenal ulcer accompanied by pyloric stenosis.
    Hirschsprung in 1888 coined the term "pyloric stenosis" and believed that pyloric narrowing was congenital.  However, HPS is not found in utero or at birth. Most cases present between the second and sixth week of life.  The cause of circular muscle hypertrophy remains unknown, probably secondary to abnormal innervation of circular muscles and possibly related to lack of nitric oxide synthase activity.  Genetic factors are also important in HPS, since it is more common in babies with affected parents or siblings.  HPS is more common in boys than in girls (4:1) and in white than in black or oriental children.  The often-quoted increased incidence of HPS in first-born babies is probably not correct. 
    Projectile non-bilious emesis which may be blood tinged secondary to gastritis is the common presentation.  Patients may present with jaundice, metabolic alkalosis and dehydration.   The diagnosis of HPS can be made on clinical grounds by palpation of the hypertrophied circular muscle (olive) in 80% of cases in babies with appropriate history.  If HPS is the presumptive diagnosis, US is the examination of choice, with sensitivity and specificity approaching 100%.  For other causes of vomiting, including GE reflux or malrotation, UGI is the study of choice.  On US, the thickness of the muscle measured from the outer edge of the echogenic mucosal complex to the outer edge of the muscle is the most sensitive and specific sign of HPS.       Recent work has shown that a muscle thickness of 3-mm or greater is virtually 100% specific for HPS [Figure 23A].  Measurements should be made on a midline longitudinal view, through the midportion of the pylorus.  Overdistention of the stomach may push the pylorus posteriorly and make it difficult to visualize; in this case the stomach needs to be decompressed with a nasogastric tube.  Most babies with HPS will have pyloric lengths of >16-mm, but some patients without HPS will have lengths >16-mm.  Thus, the diagnosis should not be made on channel length alone [Figure 23B].  The plain film may show a "caterpillar appearance" of the stomach secondary to deep peristaltic wave [Figure 23C].  UGI shows elongation and narrowing of the pyloric channel with indentation on the antrum and duodenal bulb [Figure 23D].  Various signs have been described: Double track sign, teat sign, mushroom sign and beak sign. The treatment of HPS is Ramstedt pyloromyotomy [Figure 23E].
Antral hyperplasia secondary to Prostaglandin E therapy in patients with ductal dependent congenital heart disease is an iatrogenic cause of gastric outlet obstruction in the neonatal period and may mimic HPS.  Symptoms usually resolve after the discontinuation of Prostaglandins.

Case:  A premature infant at 4 weeks of age developed vomiting.  Supine film of the abdomen showed pneumatosis intestinalis [Figure 24A].  Work up with ultrasound confirmed a diagnosis of HPS [Figure 24B].

Hirschsprung Disease:

    Hirschsprung disease is a common cause of all neonatal bowel obstruction, accounting for one third of all cases [Figure 25]. The incidence of Hirschsprung disease is 1 in 5000 live births and increases to 3.6% in families with one affected male and to 8% when a female has been affected.  Hirschsprung disease is three or four times as common in boys as in girls and, for unknown reasons, is very rare in premature infants.  In the uncommon total colonic variant, the incidence in boys and girls is nearly equal with a strong hereditary tendency.  Patients present in the neonatal period 80% of the time, with presenting symptoms including delay in passage of meconium, abdominal distension, constipation and bilious vomiting.  Twenty percent of the patients have associated abnormalities including: Down syndrome (8%), cardiac defects (8%), GU abnormalities (6%), GI anomalies (4%).  GI anomalies can include: colonic atresia, imperforate anus, and neurocristopathies. Neurocristopathies can occur singularly or in combination with neurocristopathic syndromes such as neuroblastoma, pheochromocytoma, neurofibromatosis, Waardenburg's syndrome, and multiple endocrine neoplasia II and Ondine curse or congenital central hypoventilation syndrome (CCHS).
    The histopathological criterion for diagnosis of Hirschsprung disease is absence of the ganglion cells of the myenteric plexus; this results in a narrowed aganglionic segment and markedly dilated segment proximal to the distal obstruction. The myenteric ganglion cells arise from the neural crest and migrate cephalocaudally along the vagal trunks through the intestines.  An early arrest in the migration between the seventh and twelfth weeks of gestation leads to Hirschsprung disease, and can affect a variable length of the colon and the small bowel.  Aganglionosis affecting the small bowel is rare, occurring in approximately 3% of the patients.  The transition zone from abnormal to normal ganglionic bowel is found in rectosigmoid or sigmoid colon in 65%, the descending colon in 14%, the rectum in 8% and the more proximal large bowel in 10% [Figure 26].
Eighteen percent of patients with disease develop enterocolitis during the first 3 months of life, and enterocolitis can develop after surgery [Figure 27]. Mortality is as high as 30%; some of these patients will have pseudomembranous colitis that can be rapidly fatal without prompt treatment.
    Another well-documented complication of Hirschsprung disease, occurring in 4% of patients, is perforation of the bowel.  This most commonly involves the proximal colon (68%), the appendix (17%), or distal small bowel (6%).  This complication is most commonly associated (62%) with total aganglionosis, and generally occurs by 4 months of age.   At the time of perforation, the neonate may have no other findings of aganglionosis, and thus the true diagnosis may not be considered.  Therefore, unexplained perforation of the colon, appendix or small bowel is another indication for biopsy to exclude Hirschsprung disease.

Pneumatosis Intestinalis in Children with Acquired Immune Deficiency Syndrome (AIDS):

    In children with AIDS, GI symptoms are due primarily to acute and chronic enteric infections, and much less often to GI neoplasms.  Imaging findings in children with AIDS are, for the most part, similar to those found in adults.  Esophagitis due to Candida, cytomegalovirus (CMV) and herpes simplex (HSV) can occur.  CMV can also involve the stomach and colon.  CMV colitis is often quite severe and may result in pneumatosis, stricture, toxic megacolon, and perforation.  Chronic diarrhea is one of the most disabling manifestations of AIDS and other etiologies include Cryptosporidium, Isopora belli, Salmonella, Shigella, Campylobacter, and Giardia.  The pneumatosis in children with AIDS characteristically involves the cecum and right colon and most of the patients recover with conservative management.  Immunodeficiency is assumed to play the same role as immunosuppression in causing lymphoid depletion and loss of bowel wall integrity. 

Case:  A 16 month old boy with systemic manifestations of AIDS for 10 months presented with fever, bilious vomiting and abdominal distention.  Plain films of the abdomen revealed pneumatosis intestinalis diffusely involving the large bowel [Figure 28].   The patient was treated conservatively and the pneumatosis resolved within 3 days.   No organisms were isolated from the blood or stool during the hospitalization, despite chronic CMV infection.

Pneumatosis Intestinalis Secondary to Rotavirus:

    Acute enteric infection may be the most prevalent infectious disease of humans and is probably the leading cause of death in the world.  Microorganisms responsible for acute diarrheal illnesses include viruses (rotavirus, parvovirus, coxsackievirus, and echovirus), bacteria (Campylobacter jejuni, salmonella, shigella, Escherichia coli, yersinia, staphylococcus aureus, and clostridium perfringens), and parasites (Giardia lamblia, entamoeba histolytica). 
    Viruses are a major cause of childhood morbidity and mortality worldwide.  Mortality rates are low in developed countries but approach 1,000,000 annually in young children in developing countries.  Rotavirus infections occur repeatedly in humans from birth through old age. Rotavirus can be classified into groups A-E according to antigenic groups on VP6, the major capsid antigen.  Only groups A, B, and C rotaviruses have been shown to infect humans, and most human rotavirus disease is caused by group A viruses.   The virus is highly infectious and appears to retain infectivity over many months.   Most episodes are asymptomatic or associated with mild enteric symptoms.   Infections in young children can be accompanied by severe life-threatening diarrhea, most commonly with the primary infection.  Children with viral gastroenteritis generally present with watery, non-bloody diarrhea, often with vomiting and low grade fever.  Disease is self-limited and treatment is to correct dehydration from excessive diarrhea.  Infection with rotavirus can be verified by electron microscopy, immunoabsorbent assay of stool specimens, or with complement fixing antibody titers.

Case:  A 6 month old child presented with diarrhea and bloody stools.  Supine abdominal film demonstrate pneumatosis [Figure 29]. The patient was kept NPO and given fluid resuscitation, and recovered without any complications.

Pneumatosis Intestinalis Secondary to Salmonella Gastroenteritis:

    The vast majority of salmonella infections in the United States are caused by serotypes not specifically adapted to human or animal host, whereas the most frequent isolate in developing countries is S. typhi, which is highly adapted to human hosts.  The number of isolates reported in the United States has been increasing steadily since 1975, largely a result of outbreaks associated with the mass production of food products (particularly poultry), which are frequently contaminated.  Salmonella infection occurs when ingested organisms bypass gastric defenses, multiply within the intestinal lumen, and penetrate the intestinal mucosa stimulating intracellular accumulation of cyclic adenosine monophosphate (cAMP) that causes massive Na+ and Cl- secretion into the gastrointestinal lumen.  Organisms multiply within the macrophages of the reticuloendothelial system.   They may then disseminate via the systemic circulation. 
    The clinical and pathological manifestations are subdivided into four syndromes:
        1)   gastroenteritis,
        2)   enteric fever,
        3)   bacteremia with or without disseminated disease,
        4)   asymptomatic carriage. 
    Serious complications of bacteremic infection include infections of the aorta, endocardium, bone and meninges.  Salmonella infection is particularly severe in patients who have AIDS, leukemia, lymphoma, immunodeficiency of other causes, inflammatory bowel disease, and macrophage dysfunction.  Diagnosis is based on the culture of the organism from appropriate sites.

Case: A 7 month old male presented with vomiting, diarrhea, and bright red stool per rectum.  Abdominal films showed pneumatosis and no free air [Figure 30].  Stool cultures were positive for salmonella.  The patient was treated conservatively with IV fluids; no antibiotics were given as this may increase the incidence of carrier states.   Pneumatosis resolved by the third day.

Conclusion:

    As more and more benign etiologies for pneumatosis intestinalis are described in the literature, it is very important for the radiologist to understand the pathophysiology of pneumatosis and recognize the findings on different imaging modalities.  With appropriate clinical history, the radiologist plays a crucial role in differentiating between medical and surgical causes of pneumatosis intestinalis and suggesting appropriate imaging studies or follow up.