Ulcers of the small intestine

There are many causes of ulcers of the small intestine (Table 28.1). Primary (idiopathic) small bowel ulcers are diagnosed when other identifiable causes of small bowel ulcers are eliminated. Seventy‐five percent are located in the middle to distal ileum. Symptomatic complications include bleeding, perforation, and obstruction. The ulcers vary in size from 0.3 to 5 cm and usually have sharp, demarcated borders. The diagnosis is sometimes made with radiological studies, such as small bowel follow‐through (Figure 28.1), enteroclysis, or more commonly computed tomography (CT) or magnetic resonance (MR) enterography (i.e., distension of small bowel loops achieved perorally without intubation).

Advances in endoscopic techniques allow improved visualization of the small bowel mucosa, leading to more frequent identification of small bowel pathology. Push enteroscopy is a useful adjunct for the diagnosis of small intestine lesions in the proximal third of the small intestine. With the advent of wireless capsule endoscopy, visual images can be captured from the entire small bowel, though localization of abnormal findings is not always accurate. Wireless capsule endoscopy is superior to push enteroscopy and enteroclysis for the detection of small intestinal ulcers because it allows evaluation of almost the entire small bowel mucosa. When findings on wireless capsule endoscopy need further evaluation, deep small bowel enteroscopy for diagnosis, biopsies, and therapeutic interventions is now possible using single‐balloon, double‐balloon, or spiral techniques. When combined with a retrograde approach, complete small bowel visualization can sometimes be achieved. Intraoperative enteroscopy with laparotomy or laparoscopy remains a valuable adjunct in difficult cases, or when findings on other tests suggest the need for resection of a diseased small bowel segment.

Therapy is dictated by the severity of complications. Perforation and bleeding usually necessitate surgical resection.

Many medications have been known to cause ulcers and strictures of the small intestine (Table 28.2) and among them nonsteroidal antiinflammatory drugs (NSAIDs) are recognized as common causes. NSAID‐associated intestinal injury primarily affects the distal small intestine, which leads to diagnostic confusion with Crohn’s disease.

Other medications implicated as ulcerogens include enteric‐coated potassium chloride, ferrous salts (Figure 28.2), digoxin, corticosteroids, sodium polystyrene sulfonate (Kayexalate®), cytarabine and other chemotherapeutic agents, and clofazimine. Parenteral gold therapy has been associated with enterocolitis characterized by edema and ulceration of the ileum. Ischemic damage can result from drugs that interfere with autonomic regulation of vascular supply to the bowel (Figure 28.3; see Table 28.2), or with the coagulation process, resulting in intravascular thrombus formation (Figure 28.4). On the other hand, anticoagulants can cause ulceration from intramucosal and transmural hematoma formation with mucosal pressure necrosis (Figure 28.5). Drug smugglers sometimes ingest packets of illicit drugs for transport to avoid detection (body packer; Figure 28.6), the rupture of which can result in overwhelming toxicity from the drug and often death of the smuggler.

Behçet syndrome is associated with intestinal ulceration in less than 1% of patients. These patients have multiple deep ulcers, often bleeding or penetrating, in the ileocecal region. Microthrombosis and vasculitis with intestinal ischemia can result in intestinal ulceration in systemic lupus erythematosus. Mesenteric vasculitis with small bowel ischemia and stricture formation has been reported in rheumatoid arthritis, scleroderma, polyarteritis nodosa (Figure 28.7), Henoch–Schönlein purpura, granulomatosis with polyangiitis (Figure 28.8), giant cell arteritis, Churg–Strauss syndrome, and Sézary syndrome. Spasm of the mesenteric arteries (see Figure 28.3), sometimes induced by drugs such as ergot or cocaine, can cause mesenteric ischemia and result in ulceration if prolonged. Thrombosis of the mesenteric veins resulting from many conditions, including hypercoagulable states and collagen vascular diseases, can cause transmural hemorrhage, mucosal ulceration, or even perforation of the bowel (see Figure 28.4). Angiodysplasia consists of ectatic submucosal blood vessels with a thin, overlying mucosal layer (Figure 28.9), the erosion or rupture of which can result in ulceration and gastrointestinal bleeding. Radiation damage to the intestine can result in fibrosis of the submucosal layers and vascular insufficiency with the formation of intraepithelial telangiectasia (Figure 28.10). Stricture formation can result in bowel obstruction, sometimes necessitating surgical intervention.

Cryptogenic multifocal ulcerous stenosing enteritis is an idiopathic syndrome consisting of intermittent bouts of intestinal obstruction and ulcerative stenosis, which can be steroid responsive. Radiological findings include multiple short strictures, predominantly in the ileum, with CT and MRI contrast enhancement in a layered pattern. Patients have a chronic and relapsing course but share no other characteristics of Crohn’s disease.

Chronic ulcerative jejunoileitis (CUJ) is a rare clinical syndrome which occurs most frequently among patients with long‐standing celiac disease in the sixth or seventh decade of life. It is characterized by malabsorption, abdominal pain, and multiple nonmalignant ulcers of the small intestine. Villous atrophy, which is believed to be related to infiltration by activated T cells, usually is present. Mucosal ulceration, crypt hyperplasia, and an inflammatory cell infiltrate also occur and result in malabsorption and protein‐losing enteropathy. Biopsies of the small intestine are essential to establish the diagnosis. Although oral steroids and surgical resection of severely affected bowel have been tried, no specific therapy has been shown to modulate the course of CUJ. Data suggest that CUJ may be an important risk factor for the development of enteropathy‐associated T‐cell lymphoma (Figure 28.11).

Necrotizing enterocolitis

Acute jejunitis is largely a disease of nonindustrialized nations. Outbreaks are most frequent in communities in which protein deprivation and poor food hygiene are prevalent. Clostridium perfringens type C has been established as the causative organism. The illness is characterized by bloody diarrhea, fever, and abdominal pain. Nonocclusive small intestinal ischemia results in necrosis of varying severity. Successful treatment involves early recognition, antibiotics, and surgical resection of severely affected bowel segments.

Neonatal necrotizing enterocolitis (NEC) is a disorder of unknown causation. It affects premature infants and low‐birthweight neonates and is characterized by focal or diffuse small intestine ulceration and necrosis (Figure 28.12). Implicated pathogenic etiological factors include prematurity, intestinal ischemia, infectious agents, and initiation of enteral nutrition. There is a high prevalence among infants whose mothers used cocaine during pregnancy, suggesting a pathogenic role of hypoxic and ischemic injury. Although no organism has been consistently identified with NEC, a pathogenic role for bacteria is suggested by the occurrence of epidemics within intensive care units.

Protein‐losing gastroenteropathy

The defining characteristic of protein‐losing gastroenteropathy (PLGE) is hypoproteinemia resulting from gastric or intestinal loss of plasma proteins in abnormal amounts. A number of intestinal disorders have been implicated in the pathogenesis (Box 28.1, Figures 28.13 and 28.14; see also Figure 28.11). The diagnosis is established with documentation of excessive intestinal protein losses by means of measuring fecal α1‐antitrypsin clearance. There is no specific therapy for PLGE, and management of the primary condition is the only effective remedy.