para>The infantile form of pneumatosis intestinalis (PI) is often found as a manifestation of fulminant, acute necrotizing enterocolitis (NEC) associated with prematurity and frequently leads to bowel infarction, perforation, and high mortality. ‚
EPIDEMIOLOGY
- Bimodal distribution with peaks in premature infants and adults 41 to 50 years old
- Studies suggest a male-to-female predominance with ranges reported from 1.9:1 to 5:1.
Incidence
3/10,000 individuals (adult autopsy studies) ‚
Prevalence
No population-based studies provide prevalence data. ‚
ETIOLOGY AND PATHOPHYSIOLOGY
- Etiology is unknown but likely multifactorial. Several hypotheses have been proposed.
- Mechanical theory: Gas is transmitted through a mucosal defect in the GI tract so that air dissects between tissue layers of the bowel wall. Peristalsis propagates gas to distant sites.
- Bacterial theories
- Bacteria (such as Escherichia coli and Clostridia) enter the bowel wall through mucosal defects and produce gas.
- Intraluminal bacterial overgrowth of fermenting bacteria leads to hydrogen gas accumulation, diffusion through the bowel wall, and intraluminal air trapping.
- Pulmonary theory: In patients with chronic bronchitis, asthma, or emphysema, alveoli rupture and microscopic air enters the mediastinal space-traveling along the great vessels into the retroperitoneum. Air then tracks along the bowel mesentery until it reaches the bowel and accumulates.
- An inflammatory reaction can occur as air is surrounded by histiocytes and macrophages. Over time, a histiocytic border with fibrosis creates air cysts within the bowel wall.
Genetics
No clear genetic linkage has been reported. Two case studies have reported pneumatosis intestinalis in families. ‚
RISK FACTORS
- Prematurity
- Male
- Medications such as lactulose, high-dose steroids, alpha glucosidase inhibitors for diabetes mellitus type 2 (acarbose and miglitol), and chemotherapy agents (specifically daunorubicin, cytosine arabinoside, 5-fluorouracil, bevacizumab, sunitinib, and methotrexate)
- Organ transplantation
- Recent endoscopy, sigmoidoscopy, ERCP, or colonoscopy
- Immunosuppression
- Exposure to trichloroethylene
- Administration of infant formula; lack of administration of breast milk
COMMONLY ASSOCIATED CONDITIONS
- NEC
- Peptic ulcer disease
- Asthma; pulmonary fibrosis; chronic obstructive pulmonary disease; cystic fibrosis
- Chronic hemodialysis
- AIDS
- Graft-versus-host disease
- Inflammatory bowel disease
- Intestinal tuberculosis
- Gastric cancer
- Scleroderma
- Blunt abdominal trauma
- Pseudomembranous colitis (Clostridium difficile infection)
- Diverticulitis
- Vascular disease
DIAGNOSIS
Most adult patients are asymptomatic. Often found incidentally on clinical imaging ‚
HISTORY
- Symptoms " ”dependent on location (1)
- Small intestine
- Vomiting 60%
- Abdominal distention 59%
- Weight loss 55%
- Abdominal pain 53%
- Diarrhea 27%
- Large intestine
- Diarrhea 56%
- Hematochezia 50%
- Abdominal pain 32%
- Abdominal distention 28%
- Constipation 26%
- Symptomatic patients most often present with crampy, diffuse abdominal pain.
- If the gaseous cysts result in bowel obstruction, patients present with nausea, vomiting, and abdominal distention.
- Pediatric patients with necrotizing enterocolitis may present with apnea, bradycardia, lethargy, fever, bilious vomiting, diarrhea, and rectal bleeding.
PHYSICAL EXAM
- Findings in severe cases
- Tense, distended abdomen
- Muscular guarding with palpation
- Resistance to palpation of the abdomen
- Decreased bowel sounds
- Physical exam findings seen with commonly associated conditions
- Pulmonary disease: clubbing, end-expiratory wheezing, inspiratory rales
- Immunodeficiency: oral thrush, skin lesions
- Vascular disease: decreased pedal pulses, carotid bruits
- Necrotizing enterocolitis: abdominal distention, tenderness, and abdominal wall erythema
DIFFERENTIAL DIAGNOSIS
- Life-threatening (acute abdomen)
- Necrotizing enterocolitis (infants)
- Intestinal ischemia/infarction
- Intestinal perforation
- Typhlitis
- Caustic ingestion
- Benign causes/associations
- Pulmonary disease
- Chemotherapy
- Bone and solid organ transplant
- Infectious
- Pneumatosis intestinalis must be distinguished from other types of intramural lesions (polyposis, colitis profunda cystic, lymphoma, lipoma, and pseudopolyps associated with ulcerative colitis).
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Lab tests may reveal underlying cause.
- CBC, CMP, amylase, lipase, lactic acid, ABG (if critically ill), cultures (if septic)
- Concerning findings include:
- Leukocytosis
- Arterial blood gas PO2 <7.3
- Amylase >200 IU/L
- Serum bicarbonate <20 mmol/L
- Elevated serum lactic acid >2 mmol/L
- Infants with NEC may have respiratory and metabolic acidosis, DIC, thrombocytopenia, and neutropenia.
- Imaging is how the diagnosis is most typically made.
- Plain abdominal radiographs
- Definitive in infants with suspected necrotizing enterocolitis
- Dilated loops of bowel in early stages
- Left lateral decubitus films may show pneumoperitoneum with bowel perforation.
- A sentinel loop (bowel in fixed position) suggests necrosis.
- Water-soluble contrast radiography (not usually required) may show filling defects in the lumen, with protrusion of air in the bowel wall.
- Ultrasound (not usually required) may show bright, echogenic foci.
Follow-Up Tests & Special Considerations
- Computed tomography (CT) is the test of choice to establish a definitive diagnosis of PI in adults and often helps to identify the underlying cause. CT is not needed for infant PI (plain films are sufficient).
- CT findings used to stratify disease (2)[B].
- Worrisome findings: bowel wall thickening, free peritoneal fluid, extent of air diffusion, portal venous gas, and peri-intestinal soft-tissue stranding
Diagnostic Procedures/Other
Exploratory laparotomy or diagnostic laparoscopy ‚
Test Interpretation
- Gross pathology: bluish gas-filled blebs
- Microscopic pathology: cysts with surrounding histiocytes, neutrophils, lymphocytes, eosinophils, granulomas, and fibrosis
TREATMENT
GENERAL MEASURES
- A management algorithm for adult PI has been suggested (3)[B] with a positive predictive value of 100% for surgical pathology.
- Critically ill, unstable patients should be resuscitated, and surgery considered.
- Patients with mechanical disease (intussusception, trauma, volvulus, bowel obstruction, diverticulitis, or iatrogenic bowel injury) should be managed medically or surgically according to the specific cause
- Other patients are risk stratified according to a vascular disease score.
- 0.5 points each for smoking, diabetes, hypertension, hyperlipidemia
- 1 point each for abnormal abdominal exam and small bowel pneumatosis
- 2 points each for coronary disease, peripheral vascular disease, low flow state to gut (CHF, sepsis, pressors, etc.), venous occlusion, and vasculitis
- Vascular score >6
- Suggests mesenteric ischemia
- Exploratory laparotomy with resection of necrotic bowel and revascularization should be considered if surgical candidate.
- Angiography with thromboembolectomy, angioplasty and/or stenting may be an initial option if there is no necrotic bowel
- Vascular score 4 to 6
- Mesenteric ischemia possible
- Consider minimally invasive strategies to further evaluate and treat (angiography, endoscopy, laparoscopy).
- Vascular score <4
- Likely benign finding
- Observation with medical management. Consider angiography for further evaluation if clinical status indicates.
Pediatric Considerations
NEC is initially managed medically with NPO, TPN, antibiotics, and supportive care.
Surgery is indicated with intestinal perforation or if patients deteriorate despite adequate medical management.
‚
MEDICATION
First Line
- Discontinue offending medications.
- Metronidazole 500 TID for up to 3 months if symptomatic or until documentation of PI resolution. Tetracycline (adults only), ampicillin, gentamicin, clindamycin, and vancomycin have also been used.
- Duration of therapy is not well established.
DIET
- A trial of an elemental diet for 2 weeks can help resolve (5)[C].
- PI may recur when regular diet is resumed.
Pediatric Considerations
Start breast milk (preferred) or elemental formula 7 days after pneumatosis resolves.
‚
ADDITIONAL THERAPIES
- Endoscopic puncture and sclerotherapy (5)[C]
- Oxygen therapy (5)[C]
- Oxygen is toxic to gas-forming anaerobic bacteria.
- Breathing oxygen-concentrated air creates gradient for non-oxygen gases in cysts to diffuse into bloodstream.
- Deliver 55 " “75% humidified oxygen to achieve a PO2 of 200 to 300 over 4 to 10 days.
- Hyperbaric oxygen at 2.5 atmospheres for a duration of 2.5 hours repeated over the course of 3 days
SURGERY/OTHER PROCEDURES
- Angiography can be used for endovascular intervention with thromboembolectomy, angioplasty, and/or stenting.
- The most common surgical treatment is an exploratory laparotomy with bowel resection. Second-look operations may be necessary to assess remaining bowel for viability.
- Doppler can be used intraoperatively to assess mesenteric blood flow.
ISSUES FOR REFERRAL
- PI with hemodynamic instability or an acute abdomen warrant immediate surgical referral.
- Portal venous gas with PI requires immediate surgical referral (75% of patients with portal gas have bowel infarction).
- Patients with lactic acidosis, elevated amylase levels, and/or intractable obstructive symptoms should have a surgical evaluation.
- Necrotizing enterocolitis in a neonate necessitates early, aggressive therapy (including NICU transfer, nasogastric decompression, intravenous fluids, and antibiotics). Pediatric surgery should be consulted immediately for all neonates with pneumatosis intestinalis.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Patients with incidental PI should be admitted if they have other concerning symptoms such as pain, nausea, vomiting, obstipation, signs of an acute abdomen or hemodynamic instability. ‚
IV Fluids
Aggressive IV fluid hydration in patients who are hemodynamically unstable. ‚
Nursing
Telemetry for hemodynamically unstable patients. ‚
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Serial abdominal exams
- For asymptomatic patients, follow-up imaging is not required.
- Repeat imaging for recurrent symptoms.
PATIENT EDUCATION
- Advise adult patients that PI is most commonly benign.
- Advise patients of warning signs of bowel ischemia.
PROGNOSIS
- The prognosis for asymptomatic patients is good.
- High mortality with bowel necrosis or perforation.
COMPLICATIONS
- Volvulus
- Pneumoperitoneum
- Sepsis
- Intestinal obstruction
- Severe rectal bleeding
REFERENCES
11 Jamart ‚ J. Pneumatosis cystoides intestinalis. A statistical study of 919 cases. Acta Hepatogastroenterol (Stuttg). 1979;26(5):419 " “422.22 Olson ‚ DE, Kim ‚ YW, Ying ‚ J, et al. CT predictors for differentiating benign and clinically worrisome pneumatosis intestinalis in children beyond the neonatal period. Radiology. 2009;253(2):513 " “519.33 Wayne ‚ E, Ough ‚ M, Wu ‚ A, et al. Management algorithm for pneumatosis intestinalis and portal venous gas: treatment and outcome of 88 consecutive cases. J Gastrointest Surg. 2010;14(3):437 " “448.44 Downard ‚ CD, Renaud ‚ E, St Peter ‚ SD, et al. Treatment of necrotizing enterocolitis: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg. 2012;47(11):2111 " “2122.55 Heng ‚ Y, Schuffler ‚ M, Haggitt ‚ R, et al. Pneumatosis intestinalis: a review. Am J Gastroenterol. 1995;90(10):1747 " “1758.
ADDITIONAL READING
- Ho ‚ LM, Paulson ‚ EK, Thompson ‚ WM. Pneumatosis intestinalis in the adult: benign to life-threatening causes. AJR Am J Roentgenol. 2007;188(6):1604 " “1613.
- Khalil ‚ PN, Huber-Wagner ‚ S, Ladurner ‚ R, et al. Natural history, clinical pattern, and surgical considerations of pneumatosis intestinalis. Eur J Med Res. 2009;14(6):231 " “239.
CODES
ICD10
K63.89 Other specified diseases of intestine ‚
ICD9
569.89 Other specified disorders of intestine ‚
SNOMED
pneumatosis cystoides intestinalis (disorder) ‚
CLINICAL PEARLS
- Pneumatosis intestinalis is mostly an incidental, benign finding in adults " ”examine for signs of bowel perforation.
- Abdominal CT scan is diagnostic test of choice in adults.
- Single best test to identify PI (and potential NEC) in neonates is an abdominal plain film.
- Noninvasive therapies include diet changes, oxygen therapy, and nasogastric decompression. Surgery is indicated based on clinical findings.