Rudolph's Pediatrics, 22nd Ed.

CHAPTER 412. Vascular, Systemic, and Other Disorders Affecting the Gastrointestinal Tract

Grzegorz Telega, Vincent F. Biank, and B U.K. Li

GASTROINTESTINAL VASCULAR DISORDERS

ISCHEMIC BOWEL DISORDERS

Ischemic bowel disease is the term used to describe disorders that cause insufficient blood flow to the gastrointestinal tract. (Table 412-1).1 Arteriosclerotic vascular disease is the major cause of ischemic bowel disease in adults but is extremely rare in children. Most pediatric cases of acute childhood ischemic bowel disease result from extrinsic obstruction, hyper-coagulable states, or following hypovolemic shock.2

Clinical findings with mesenteric vascular insufficiency consist of postprandial colicky periumbilical pain, with symptoms that are far worse than would be expected from physical examination of the abdomen. Similar symptoms can also be experienced with ischemia of the spleen or omentum. Acute vascular insufficiency results in nonspecific findings including ileus, bilious vomiting, and mucosal necrosis with hematemesis or hematochezia. Symptoms may worsen following reperfusion. Ischemic injury should be considered if symptoms persist or worsen following an acute insult such as shock or surgical obstruction. Chronic vascular insufficiency may result in protein-losing enteropathy, steatorrhea, or carbohydrate malabsorption.

Diagnosis of ischemic bowel disease or other vascular disorders of the bowel requires a high degree of suspicion and is mainly dependent upon the history and physical examination.3 Confirmatory studies may include gastric tonometry, Doppler ultrasound, and abdominal computerized tomography (CT). In some cases, mesenteric angiography may be necessary to establish the diagnosis. Due to the rarity of ischemic disease in childhood, endoscopic findings (see eFig. 412.1 ) of exudate are often misinterpreted as being due to inflammatory bowel disease. Biopsy generally shows acute inflammatory changes. Chronic ischemia may be associated with fibrosis. Treatment depends upon the underlying cause and may include resection of involved bowel, anticoagulation therapies, and interventional radiographic therapies.

Rarely, symptoms similar to ischemic bowel disease result from mesenteric venous inflammation. Mesenteric inflammatory venoocclusive disease is characterized by extended thrombophlebitis and fibrous organized thrombosis of multiple veins, not the arteries.4 Diagnosis is usually made on pathology of bowel resected for ischemia.

SYSTEMIC VASCULITIC DISEASES

Systemic vasculitic diseases (especially polyarteritis nodosa), anatomical malformations of the mesenteric artery, degas disease, and dermatomyositis are the most common chronic or recurrent causes of bowel ischemia in children.2Dermatomyositis can be associated with mesenteric vasculitis, intestinal ulcerations, and perforations. Other collagen vascular disorders, including polymyositis, polyarteritis nodosa, and systemic lupus erythematosus, are occasionally associated with mesenteric arteritis. Degos disease is an obliterative endarteritis that affects small to medium-sized vessels and can be associated with spontaneous perforation of the bowel.

Henoch-Schönlein purpura is a systemic vasculitis with deposition of IgA immune complexes in postcapillary venules throughout the body, as discussed in detail in Chapter 472. Gastrointestinal symptoms of diffuse abdominal pain, vomiting, and hematochezia may be observed several weeks before onset of the palpable purpuric skin lesions. Endoscopy displays purpuric lesions of the small bowel and colon.5Intussusception occurs in approximately 10% of children with Henoch-Schönlein purpura and abdominal pain; bowel perforation and development of bowel stricture are less common. Pancreatitis and cholecystitis have been reported. Corticosteroid treatment may decrease the severity of GI symptoms, but treatment may mask symptoms of perforation and does not prevent renal complications. The benefits of corticosteroid treatment remain controversial.

VASCULAR MALFORMATIONS

Vascular malformations are a rare cause of painless bleeding of varying severity in children. Angiodysplasias are small vascular malformations of the gut. The lesions are often multiple and frequently involve the cecum or ascending colon, although they can occur at other places. In childhood, these are most commonly associated with Turner syndrome6 or von Willebrand’s syndrome.7 Diagnosis of angiodysplasia is often accomplished with endoscopy. Treatment options include endoscopic interventions (including double-balloon enteroscopy and ablation therapy), estrogen/progesterone therapy, or occasionally surgery.

Table 412-1. Disorders Associated with Gastrointestinal Ischemia

Surgical obstruction

Volvulus/malrotation

Incarcerated hernias

Intussusception

Mass lesions involving mesenteric artery

Hypercoagulable states

Hypovolemic shock

Burns

Protein-losing enteropathy

Genetic thrombolytic disorders

Diabetic ketoacidosis

Drugs

Dihydroergotamine

Vasopressin

Cocaine

Vasculitis

Polyarteritis nodosa

Degos disease

Dermatomyositis

Mesenteric inflammatory venoocclusive disease

Henoch-Schönlein purpura

Hemolytic uremic syndrome

Arteriovenous malformations are in the majority of cases a congenital disorder consisting of a connection between veins and arteries. They may be located throughout the gastrointestinal tract, and bleeding into the intestinal tract may be severe (Fig. 412-1). Lesions may be diagnosed by endoscopy, angiography, or at surgery. Dieulafoy’s lesion is an uncommon cause of major gastrointestinal bleeding and may be difficult to recognize. It consists of an arteriole that protrudes through a tiny mucosal defect, usually within 6 cm of the gastroesophageal junction on the lesser curve of the stomach.

HEMOLYTIC UREMIC SYNDROME

Hemolytic-uremic syndrome is a systemic vasculitis resulting from intravascular platelet activation, causing thrombocytopenia and renal insufficiency, as described in Chapter 472. In approximately 95% of cases, a prodromal gastroenteritis precedes the onset of systemic symptoms.8 In 75%, bloody diarrhea is the presenting symptom. Hemolytic-uremic syndrome may be precipitated by gastrointestinal (GI) infection with Escherichia coli 0157:H7, Shigella, Campylobacter, Yersinia, or Salmonella. Patients usually present with severe abdominal pain and bloody diarrhea. Symptoms may be significant enough to warrant surgical consultation. Findings on radiographic contrast studies include thumbprinting and ulcerations, which may be consistent with an ischemic process. Colonic perforation occurs in 1% of patients with hemolytic uremic syndrome. Colonic perforation is more likely to occur in patients who are younger than 2 years and require dialysis. Late GI complications of stricture and fistula have been reported. Patients with severe GI symptoms should receive parenteral nutrition and not be fed until symptoms resolve. Pancreatitis rarely occurs.

FIGURE 412-1. Arteriovenous malformation of the small intestine (black arrows) in a patient with Turner syndrome, shown by images from a capsule endoscopy

AMYLOIDOSIS

Amyloidosis is a disorder with accumulation of amyloid in the bowel. This may occur as either a primary or secondary process. In children, it usually is associated with hemodialysis, familial Mediterranean fever, juvenile rheumatoid arthritis, cystic fibrosis, Crohn disease, or autoimmune enteropathy. Most patients with amyloidosis have proteinuria. Approximately two thirds of patients with secondary amyloidosis have gastrointestinal involvement, with symptoms of obstruction, impaired motility, or ischemia resulting from infiltration around blood vessels.9 The presence of gastrointestinal symptoms in combination with proteinuria in a patient undergoing hemodialysis or with a chronic inflammatory condition should raise the suspicion of amyloidosis. Diagnosis is based on histological evaluation of bowel biopsy that reveals submucosal and mucosal amyloid deposition when stained with special amyloid stains.10 Treatment with colchicine reduces the amyloid deposition in familial Mediterranean fever, but useful therapy for amyloidosis resulting from other etiologies is lacking.

RADIATION ENTERITIS

Radiation enteritis most often follows radiation therapy for malignancy, although it may occur following other radiation exposures. Acute injury to the rapidly replicating bowel epithelium is common, with consequences of malabsorption causing diarrhea and vomiting in many patients. A low-residue, low-lactose diet often is helpful in reducing symptoms during the acute phase, but if symptoms are severe, the radiation dose may need to be reduced. Acute symptoms usually resolve within 6 weeks of the completion of therapy. Chronic damage with submucosal fibrosis and obliteration of small blood vessels and lymphatics is rare in children because of the lower doses of radiation that are used in therapy for childhood tumors. Chronic symptoms of dysmotility may improve after treatment of bacterial overgrowth. Diffuse and segmental strictures have been described. Local lymphatic or vascular obstruction may require limited surgical resection. As long-term survival of childhood cancer improves, secondary malignancies due to radiation exposure, including gastrointestinal malignancies, are increasingly common.11

PNEUMATOSIS INTESTINALIS

Pneumatosis intestinalis is characterized by the finding of numerous intramural hydrogen gas-filled cysts involving any part of the gastrointestinal tract (see Fig. 412-2 and eFig. 412.2 ). In premature and newborn infants, this finding is often associated with necrotizing enterocolitis and has serious implications. In older children and adults, this rare disorder is occasionally associated with fulminant illnesses such as ischemic colitis, bowel infarction caused by midgut volvulus, or severe enteric infections. In these scenarios, pneumatosis intestinalis is commonly associated with advanced intestinal necrosis and is an ominous finding requiring intervention.

A less ominous presentation is associated with chronic pulmonary diseases such as cystic fibrosis, connective tissue diseases, gastrointestinal obstruction, chronic idiopathic intestinal pseudoobstruction, and also occurs relatively frequently in patients following cancer chemotherapy or bone marrow transplantation.13 In most of these cases, pneumatosis intestinalis is a relatively benign disorder that usually involves the left colon and is discovered incidentally during radiographic evaluation.

In otherwise asymptomatic patients, treatment is indicated only for associated illnesses because the lesions resolve spontaneously. Complications occur in a small minority of these cases and include pneumoperitoneum, intussusception, and perforation. Antibiotic treatment with metronidazole and ampicillin or oral vancomycin have been suggested, enteral or parenteral nutrition, and bowel rest have also been successful in some cases, but it is unclear whether the lesions would resolve without therapy. Surgery is indicated in fulminant cases of pneumatosis, especially in patients with metabolic acidosis or other findings suggestive of bowel necrosis on physical examination or abdominal computed tomography (CT) scan. A finding of mesenteric venous gas on plain abdominal radiographs or CT scan (which is more sensitive) is highly suggestive of bowel infarction.

MELANOSIS COLI

Melanosis coli describes an abnormality of pigmentation of the wall of the colon that is usually found at colonoscopy (eFig. 412.3 ). Brown pigment, lipofuscin, is deposited in the wall of the colon, and biopsy reveals characteristic pigment-laden macrophages within the submucosa with PAS staining. The most common cause is chronic use of anthraquinone laxatives including Senna and other plant glycosides. It is benign, and has no significant correlation with disease. No clinical symptoms appear to result from this benign disorder.14

FIGURE 412-2. Computed tomographic findings of pneumatosis intestinales; arrow shows typical intramural gas.

BEHÇET SYNDROME

Behçet syndrome is a multisystem vasculitis that manifests as a chronic relapsing, inflammatory disease classically characterized by recurrent mucocutaneous, ocular, and vascular manifestations discussed in Chapter 203. Perianal aphthosis is seen in 7% of pediatric patients with Behçet syndrome.15 The involvement of the gastrointestinal tract by Behçet syndrome may be difficult to distinguish from Crohn disease because the ileum and right colon are relatively frequent sites of involvement.16,17 Fistulas and deeply penetrating ulcers that can perforate are common. Therapy with corticosteroids, thalidomide, and inflixamb has achieved some success.18

DIVERSION COLITIS

Following various surgical procedures, bowel contents are diverted through an ostomy to prevent the passage of feces into the distal colon and rectum. This may be necessary to allow healing of perianal lesions or following acute surgical interventions for bowel perforation. Occasionally, the remaining colon epithelium becomes inflamed, causing the passage of rectal blood and mucus. A deficiency of luminal short-chain fatty acids appears to be involved in the pathogenesis of diversion colitis. Effective therapy with the instillation of short-chain fatty acids by enema leads to the resolution of symptoms.19 It is important to differentiate diversion colitis from other causes of colitis such as inflammatory bowel disease because treatment of diversion colitis is by reanastomosis, and treatment of inflammatory bowel disease is focused on either medical therapies or surgical resection.

GRAFT VERSUS HOST DISEASE

Graft versus host disease (GVHD) is discussed in Chapter 133. GVHD most frequently occurs following bone marrow transplantation. Acute GVHD usually manifests at 3 to 4 weeks following transplant. Gastrointestinal symptoms may be minimal to severe with abdominal pain; profuse watery, mucoid diarrhea; protein-losing enteropathy; intestinal bleeding; and sepsis. Generally, the severity of intestinal GVHD parallels skin and liver involvement; however, some patients have gastrointestinal symptoms with minimal, if any, other findings. Because gastrointestinal infection can present in a similar fashion, this must be ruled out (see Chapter 391). Endoscopic findings range from normal to extensive mucosal sloughing with ulceration. The most prominent changes are most frequently observed in the ileum, cecum, and ascending colon. Biopsies of normal-appearing tissue often are diagnostic, whereas biopsy of severely involved tissue may be less specific. Biopsies of the rectum are more sensitive than biopsies of the upper GI tract for diagnosis of chronic GVHD.20 Treatment of acute intestinal GVHD includes treatment of the GVHD and supportive measures, including provision of appropriate enteral or parenteral nutritional support and careful attention to fluid and electrolyte balance. Octreo-tide may decrease the amount of diarrhea. Oral beclomethasone dipropionate may be preferable to prednisone because it may reduce systemic steroid effects.21

Chronic GVHD develops at 80 to 400 days after BMT and differs from acute GVHD in the time of onset, sites involved, and histologic findings in target organs. Most patients with chronic GVHD had preceding acute GVHD that either resolved or evolved into the chronic form. Gastrointestinal involvement typically includes the oral mucosa (mucositis), salivary glands (oral sicca), or esophagus. Some children present only with poor oral intake and weight loss. Esophageal findings include esophagitis (often involving the proximal and midesophagus), upper esophageal strictures and webs, and typical peptic esophagitis in the distal esophagus. Esophageal biopsies typically are infiltrated with lymphocytes, neutrophils, and eosinophils, with necrosis of individual squamous cells in the basal layer. Malabsorption may result from exocrine pancreatic insufficiency. As in acute GVHD, infectious causes of the symptoms need to be considered, including viral and fungal etiologies. Treatment consists of immunosuppressive and acid-suppressive therapy. Webs or strictures are treated with dilation.