Pneumatosis Intestinalis

Etiology

Pneumatosis intestinalis itself is not a primary disease but a clinical sign of underlying pathology. In 1998, BL Pear proposed the mechanisms behind extraluminal gas formation included bowel necrosis, pulmonary disease, and abnormal mucosal permeability. The cause of PI may also be multifactorial from pulmonary, mechanical, and bacterial causes, although mucosal integrity disruption is present in all scenarios. The condition can also further be divided into primary and secondary types. In primary pneumatosis intestinalis, the gas collection is benign in nature and creates a cystic pattern in the intraluminal wall. Secondary pneumatosis intestinalis is correlated with a pathological condition, and gas distribution appears in a more linear fashion.[2][4][5][7]

Epidemiology

Pneumatosis intestinalis occurs in approximately 0.03% of the population. Given the asymptomatic course of the majority of cases, the exact prevalence of the condition is unknown, and that 0.03% is possibly an underestimation. It can affect any age group, although it is more prevalent in older populations than in young adults and infants. Infantile PI has higher mortality than adult forms, and it is usually associated with acute necrotizing enterocolitis. In adults, PI is usually benign and found incidentally on imaging. In adults, approximately 15% of cases are primary, and 85% are secondary.[5][7][8]

Pathophysiology

Gas distribution in the extraluminal space is a multifactorial process. There are three hypotheses of pathogenesis labeled mechanical, pulmonary, and bacterial theories. The mechanical theory hypothesizes that an increase in intraluminal pressure may lead to mucosal damage. Surgical complications and endoscopies can cause blunt trauma, forcing gas from the gastrointestinal cavity into extraluminal space. Gas transmits through the tissue layers and propagates via peristalsis. Lung diseases such as asthma, interstitial pneumonia, and chronic obstructive pulmonary disease can cause alveolar rupture that may release gas into the mesenteric vasculature. The pulmonary theory states that gas can propagate caudally into the retroperitoneum and mesentery from the mediastinum.

It is hypothesized that gas migrates through the mediastinal vessels into the mesentery. Finally, the bacterial theory states gas-producing bacteria such as Escherichia coli and Clostridia species can invade the intraluminal compartments, which is supported by the decrease in gas after antimicrobial drug therapy and proximity of the gas cysts near blood vessels. In neonates, pneumatosis intestinalis is usually a radiographic sign of necrotizing enterocolitis. Risk factors include prematurity, low birth weight, and formula diet.[3][4][6][8][9]

History and Physical

The clinical presentation may vary depending on whether a patient presents with primary or secondary pneumatosis intestinalis. Primary or benign causes usually result in mild abdominal symptoms. There are reported cases where patients with primary PI presented without symptoms. However, patients with secondary pneumatosis intestinalis may present with life-threatening peritoneal symptoms, similar to that of intestinal ischemia and peritonitis. Other symptoms of secondary PI include hematochezia, tenesmus, constipation, and abdominal pain. Approximately 3% of patients presenting with PI also reported complications such as pneumoperitoneum, intestinal ischemia, and obstruction. History of abdominal laparotomy and endoscopy can be common in patients as procedures leading to mucosal disruption, causing an increase in intraluminal pressure can lead to pneumatosis intestinalis. There are also many diseases and conditions in a patient’s history that are known to be associated with PI (via the three mechanisms), including but not limited to:[3][4][6][10]

• Pulmonary disease - Asthma, chronic obstructive pulmonary disease (COPD), emphysema 
• Autoimmune - Lupus variants, polymyositis, dermatomyositis, polyarteritis nodosa, celiac sprue
• Drug-induced - Glucosidase inhibitors, corticosteroids
• Gastrointestinal - Inflammatory bowel disease (IBD), diverticulitis, colitis, Clostridium difficile infection, appendicitis, carcinoma, peptic ulcer, perforation, necrotizing enterocolitis (pediatric)
• Infectious - Human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), mycobacterium tuberculosis, 2019 novel coronavirus (COVID-19)
• Iatrogenic - Blunt abdominal trauma, endoscopy, post-surgical intestinal anastomosis, barium enema, positive end-expiratory pressure (PEEP) ventilation

Evaluation

Abdominal radiographs, computed tomography, magnetic resonance imaging, and ultrasonography are used to diagnose pneumatosis intestinalis. However, one-third of patients’ radiographs may not reveal any signs, such as thickened bowel walls containing gas. Computed tomography is the most sensitive imaging modality as it better distinguishes intraluminal air from submucosal fat and detects additional underlying causes of pneumatosis intestinalis such as portal air, colonic tissue stranding, and dilated bowel. Subsequent imaging should be performed to assess the presence and expansion of portal venous and intra-abdominal air.

Gas can be distributed in a cystic pattern as seen with pneumatosis cystoides intestinalis or linear, which is associated more with bowel ischemia and portal venous gas. A linear pattern is more in line with the secondary PI. Ling et al. reported that gas cysts can be located in the colon (46%), small intestines (27%), large intestines (7%), and stomach (5%). An endoscopy can be performed to characterize the distribution of gas formation (linear versus cystic) and to exclude any other colonic lesions. Laboratory tests play an important role in determining the treatment and management of benign versus life-threatening cases. Such laboratory exams include but are not limited to white blood cell count, lactic acid, aspartate aminotransferase, alanine aminotransferase, amylase, bicarbonate level, and alkaline phosphatase.[3][6][10][11]

Treatment / Management

There are differences in treatment options between primary and secondary pneumatosis intestinalis. Other factors influencing treatment include laboratory values and clinical presentation of the patient. Since PI is not a disease in itself but a clinical sign, treatment begins with the underlying cause. A conservative, non-surgical approach is warranted in patients without signs of any life-threatening conditions such as peritonitis and sepsis. In addition, subsequent imaging is needed for patients who are at high risk of their PI worsening into a life-threatening condition.

Ling et al. state that conservative methods include observation, hyperbaric oxygen therapy, antibiotics to inhibit intestinal bacterial infection, and endoscopy. Hyperbaric oxygen therapy alleviates symptoms by decreasing the partial pressure of gases in the venous system and facilitating gas diffusion out of the bowel wall. It also acts as a toxin against anaerobic bacteria in the intestinal tract. Hyperbaric oxygen therapy can also be supplemented with humidified oxygen via a Venturi mask or nasal cannula (4 to 6 L/min). Oxygen therapy should be used for two days after cyst disappearance in order to reduce the risk of recurrence. An antibiotic regimen used to treat PI is metronidazole 500 mg PO three times a day for up to three months. Further long-term management of PI is an elemental diet or a digestible formula diet composed of a liquid/powder form of daily nutrients. An elemental diet is completely absorbed in the intestines and reduces the production of gas by bacterial flora.

The indications for surgical intervention for PI are elevated white blood cell count, definitive imaging revealing portal venous gas, and clinical signs of sepsis or acidosis. Another more specific intervention is endoscopy with sclerotherapy for patients suffering from intestinal obstruction due to PI. Endoscopic treatment involves fine-needle aspiration of the many cysts in an attempt to exhaust the gas and relieve the intestinal obstruction. It can also be used to diagnose PI as it confirms the presence of gas-filled cysts via direct observation. Some patients may experience recurrence of intestinal obstruction due to PI. In this case, sclerotherapy of the wall after puncture may be performed to prevent the recollection or reexpansion of the cysts.[3][4][5][6][11](B3)

Differential Diagnosis

Other pathologies that are part of the differential diagnosis must be ruled out. One of the more serious conditions is bowel ischemia. Infarction must be considered as a differential diagnosis, especially in patients with vascular disease, cardiac failure, and atrial fibrillation. The clinical presentation of diffuse abdominal pain with abnormal laboratory values warrants intestinal infarction rule out. Furthermore, with bowel ischemia, underlying causes such as strangulated internal hernia, abdominal abscess, and/or ileus must be considered.[1][12]

Prognosis

Predictors for poor prognosis in pneumatosis intestinalis include:

• pH < 7.3 
• Presence of portal venous gas
• Lactate level > 2 mmol/L
• Amylase level > 200 U/L
• Bicarbonate level < 20 ml/L

Surgical intervention is considered if patients, especially over 60 years of age, present with any obstructive symptoms, signs of sepsis and shock, or radiographic evidence of portal venous gas due to the high mortality associated. As per Greenstein et al. in 2007, the presence of emesis, leukocytosis (> 12 c/mm3), and age 60 and older are poor prognostic factors leading to surgical management. Furthermore, lactic acidosis, shock, and sepsis are also associated with unfavorable outcomes, including death.[4][6][13]

Complications

Pneumatosis intestinalis is associated with several complications, which are divided into intestinal and extraintestinal manifestations. Intestinal complications are mainly obstructions caused by gas cysts. This can lead to fecal impactions, which, if left untreated, can cause perforations due to colonic ulcers from long-standing increased intracolonic pressure. Perforation can lead to acute abdomen, septic shock, peritonitis, and other life-threatening conditions.

The presence of pneumatosis intestinalis with portal venous gas usually correlates with bowel ischemia in approximately 70% of cases. Extraintestinal complications are adhesions and compression of nearby structures. Cysts can cause outpouchings that directly compress adjacent organs. Rupture of these cysts can cause pneumoperitoneum, which requires urgent surgical intervention. Complications usually occur in approximately 3% of secondary pneumatosis intestinalis. Mortality from these complications can range from 50% to 75%, especially those with bowel ischemia.[3][4][7]