Pneumatosis intestinalis (PI) is defined as the presence of gas in the bowel wall [1–4]. This imaging finding is associated with numerous conditions, ranging from benign to life threatening [1–5]. The overall incidence of PI in the general population has been reported to be 0.03% based on an autopsy series [4]. Although PI can be seen on abdominal radiographs, CT is the most sensitive imaging test for identification of PI [6]. The CT detection of PI appears to be increasing, likely as a consequence of increased use of CT technology [7]. Increased imaging detection of PI could also be due to an increased incidence of PI. Relatively new surgical procedures and medications associated with PI may be contributing to an increase in incidence of PI. The aim of this article is to describe the imaging appearance and clinical findings of PI in the adult population.

In 1754, Duvernoy wrote the first report of PI, which appeared in the French literature [8]. Since then, numerous case reports and reviews have appeared in the world literature. In 1998, Pear [5] undertook the most recent comprehensive review in the U.S. radiology literature. His classification scheme was based on the current evidence and theories regarding the cause and clinical significance of PI. In his review, PI was classified pathogenically into four categories: bowel necrosis, mucosal disruption, increased mucosal permeability, and pulmonary disease.

In this article, we divided PI into two categories: benign causes and life-threatening causes (Appendix 1). It is important to understand that PI is a sign not a disease, and it must be interpreted relative to the patient's overall clinical condition. Therefore, clinical symptoms and laboratory data provide the most important clues in determining whether PI is due to benign or life-threatening causes.

Although the cause of PI appears to be multifactorial, the exact cause is not known. Two main theories have been proposed in the medical literature. A mechanical theory hypothesizes that gas dissects into the bowel wall from either the intestinal lumen or the lungs via the mediastinum [1] due to some mechanism causing increased pressure (i.e., bowel obstruction or emphysema). A bacterial theory proposes that gas-forming bacilli enter the submucosa through mucosal rents or increased mucosal permeability and produce gas within the bowel wall [1].

Studies have shown that gas collections in the bowel wall can have a hydrogen content of up to 50%. Hydrogen is a product of bacterial metabolism and is not produced by human cells [1]. The major argument against the bacterial theory is that long-standing pneumoperitoneum can occur with PI and rarely is it associated with peritonitis [8]. A combination of both theories is also plausible. Bacterial overgrowth in the gastrointestinal tract from a variety of causes can lead to excessive hydrogen gas production, bowel distention, and subsequently, dissection of intraluminal hydrogen gas into the bowel wall.

In cases of PI due to benign causes, especially PI associated with pulmonary disease, the patients are usually asymptomatic [1–4]. Some patients may have mild abdominal discomfort, which is usually related to the underlying associated medical condition. Physical examination is rarely abnormal unless there are peritoneal signs from intestinal perforation in cases of PI due to life-threatening causes. Laboratory values in the presence of intestinal ischemia may reveal acidosis with a blood pH of < 7.3, a hyperamylasemia of > 200 IU/L, a serum bicarbonate level of < 20 mmol/L, and an elevated serum lactic acid of > 2 mmol/L [3]. A recent study found that the combination of PI and a serum lactic acid level of > 2 mmol/L was associated with a greater than 80% mortality rate [9].

Abdominal radiography and CT are the most frequently used techniques for diagnosis of PI. CT has been shown to be more sensitive than radiography at detecting PI [10–14]. CT has also been shown to be more sensitive than radiography at detection of hepatic portal and portomesenteric venous gas [12, 15, 16], the presence of which increases the possibility of PI due to life-threatening causes. Advances in CT may further improve the detection of PI and hepatic portal and portomesenteric venous gas; 16- and 64-MDCT scanners are capable of generating isotropic data sets that allow multiplanar reformations with a spatial resolution similar to or even greater than the axial plane. The ability to study the bowel wall in the coronal, sagittal, and axial planes may allow a more confident diagnosis of PI and portal venous gas.

On both radiographs and CT, PI usually appears as a low-density linear or bubbly pattern of gas in the bowel wall (Fig. 1A, 1B). It can be a combination of both linear and bubbly bowel-wall gas. There also may be circular collections of gas in the bowel wall (Fig. 2A, 2B). Occasionally, bowel contents mixed with air or air trapped between mucosal folds can mimic PI. Viewing CT images with lung windows may accentuate the detection of PI, especially in the colon [11] (Fig. 3A, 3B). Because CT is more sensitive than radiography in detecting PI, CT can be used to clarify ambiguous radiographic findings and also to search for potential causes [11].

The circular form of PI is usually benign and most often seen with pneumatosis cystoides intestinalis (PCI). Linear or bubble-like PI can be due to both benign and life-threatening causes, and its radiographic or CT appearance alone does not allow differentiation between them. In PI due to benign causes, the bowel wall is usually normal. The presence of additional findings such as bowel wall thickening, absent or intense mucosal enhancement, dilated bowel, arterial or venous occlusion, ascites, and hepatic portal or portomesenteric venous gas increases the possibility of PI due to a life-threatening cause [15, 17] (Fig. 4A, 4B, 4C). PI that is confined to a portion of the small or large bowel within a specific vascular distribution also increases the likelihood that ischemia is the cause of PI. Intraperitoneal or retroperitoneal free air can be seen with PI due to life-threatening or benign causes [6, 18–20]. The association of spontaneous pneumoperitoneum with PI has been attributed to the rupture of serosal and subserosal cysts in the bowel wall [8].

Portal venous gas is differentiated from biliary gas by its characteristic tubular branching lucencies that extend to the periphery of the liver, whereas biliary air is more central (Fig. 5A, 5B). The use of coronal reformatted images with MDCT may improve detection of portomesenteric gas owing to the oblique vertical orientation of the mesenteric vessels [15, 21].

Several reports in the literature have addressed the capability of CT of distinguishing early and nontransmural mesenteric ischemia from full-thickness and irreversible transmural infarction [17, 22, 23]. Both Kernagis et al. [23] and Weisner et al. [22] found that linear PI was seen more frequently than bubbly PI in patients with transmural bowel infarction. Furthermore, both research studies found that the detection of PI in association with portomesenteric venous gas correlated strongly with transmural bowel infarction, whereas PI without evidence of portomesenteric venous gas was frequently seen in cases of nontransmural intestinal ischemia. The overall survival rate was higher in patients with nontransmural intestinal ischemia compared with those patients with transmural intestinal infarction.

Although the discovery of hepatic portal or portomesenteric venous gas helps to distinguish between benign and life-threatening causes of PI, it may also occur with or without PI as a result of nonischemic conditions. Mesenteric abscess formation, portomesenteric thrombophlebitis, sepsis, abdominal trauma, severe enteritis, cholangitis, chronic cholecystitis, pancreatitis, inflammatory bowel disease, and diverticulitis and after gastrointestinal surgery or liver transplantation are some of the various nonischemic clinical conditions that have been associated with hepatic portal and portomesenteric venous gas [15, 21, 22, 24–27].

Sonography can also be used to detect PI [28, 29]. This technique is more commonly applied to the pediatric patient in whom avoidance of ionizing radiation is preferred [30]. PI seen on sonography has been described as linear or focal echogenic areas within the bowel wall [31]. It can also appear as a continuous echogenic ring in the bowel wall [32].

Rarely, PI can also be seen on MRI. Rabushka and Kuhlman [33] described two cases of PI seen with MR. They found circumferential collections of air adherent to or within the bowel wall that became more apparent on gradient-echo images due to blooming artifact associated with magnetic field inhomogeneities at air–tissue interfaces.

Appendix 1 lists benign causes of PI in the adult. The number of benign conditions associated with PI appears to be increasing. This observation may be the effect of increased use of cross-sectional imaging. In most cases, the natural history of PI due to benign causes is not known because there is often no imaging follow-up. Spontaneous resolution and recurrent episodes have been described in the literature [4, 8, 34]. PCI is one subset of PI that is invariably benign. PCI is characterized by circular collections of gas in the bowel wall and its mesentery [11, 34] (Fig. 2A, 2B). It almost always occurs in the colon. On barium enema studies, it can mimic polyps when viewed en face (Fig. 2B), but in profile the gas cysts can be clearly identified within the colon wall (Fig. 2B).

Pulmonary causes of PI are usually benign and range from congenital to acquired. Cystic fibrosis, asthma, and chronic obstructive pulmonary disease have a well-known association with PI [35, 36]. PI has been reported in patients who have undergone organ transplantation [37, 38]. We have encountered a number of cases (Fig. 6A, 6B, 6C) after lung transplantation [18, 39–41]. Although steroid therapy is one possible cause of PI in the post–lung transplantation period, cytomegalovirus (CMV) colitis has also been implicated as a cause of PI in the lung transplant patient. CMV colitis is a common opportunistic infection in lung transplant recipients, which can manifest as gastrointestinal disease [18]. In our experience, these patients respond well to conservative therapy that includes bowel rest and empiric antiviral medication.

Systemic diseases and intestinal disorders make up a large number of causes of PI. These include collagen vascular disease such as scleroderma [42, 43] (Fig. 7A, 7B) and inflammatory bowel disease [19, 44, 45]. John et al. [45] reported that CT evidence of PI in patients with Crohn's disease usually correlated with a higher severity of disease. However, the presence of PI in these patients did not dictate a specific course of treatment, and therapy was based on the overall clinical picture.

The association of PI with AIDS was frequently reported in the early days of the HIV epidemic [20, 46, 47]. However, this finding appears to have become less common, presumably due to the effectiveness of new medications and treatments for patients with HIV.

Iatrogenic causes can also be encountered. PI has been seen as a sequela of double-contrast barium enema [48]. There have been numerous reports of patients with PI associated with jejunostomy tubes [3, 49, 50].

Medication side effects can be an overlooked cause of unexplained PI. Corticosteroid administration is the most common cause of medication-induced PI [4]. Steroids have been shown to cause atrophy of lymphoid aggregates (Peyer patches) in the gastrointestinal tract, which can in turn lead to loss of submucosal structural integrity and allow dissection of intraluminal air into the intestinal wall. PI has been associated with medications that cause bowel distention or diarrhea. The development of PI in cancer patients has also been attributed to several chemotherapeutic agents [4, 51]. Sorbitol, lactulose, and voglibose have also been reported to cause PI. In most of these cases, PI resolved with discontinuation of the medication [4, 52–55].

Mesenteric ischemia (Fig. 4A, 4B, 4C) is the most common life-threatening cause of PI (Appendix 1). Occasionally, thromboembolization is proven as a cause of the ischemia [6] (Fig. 8A, 8B, 8C), but often the exact cause is never established. Other life-threatening causes of PI include bowel obstruction, cecal ileus, toxic megacolon (Fig. 9A, 9B), and collagen vascular diseases (which may also produce PI due to benign causes). As described, PI in the setting of organ transplantation is often benign, but it can also be life threatening, especially after bone marrow transplantation [56–58]. Acute graft-versus-host disease as a life-threatening complication of bone marrow transplantation can also lead to PI [59].

There are many benign and life-threatening causes of PI. The imaging appearance of both may look very similar. Therefore, correlation with clinical history, physical examination, and laboratory test results is the best indicator of whether PI is due to a benign or life-threatening cause. PCI is one subset of PI that is almost always benign. In cases of PI associated with suspected bowel ischemia, the additional detection of hepatic portal or portomesenteric venous gas increases the likelihood of transmural bowel infarction.

Address correspondence to L. M. Ho ([email protected]).