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ileitis

Ileitis

Ileitis also called terminal ileitis, is an inflammation of the ileum, the last part of the small intestine that joins the large intestine. Ileitis symptoms include weight loss, diarrhea, cramping or pain in the abdomen, or fistulas (abnormal channels that develop between parts of the intestine). Ileitis can be caused by a wide variety of other diseases, Crohn’s disease being the most common 1. Other causes  of ileitis include infectious diseases, effects of non-steroidal anti-inflammatory drugs (NSAIDs), spondyloarthropathies, vasculitides, ischemia, neoplasms, medication-induced, eosinophilic enteritis, abnormal growths, sarcoidosis, amyloidosis, and others 1.

Crohn’s disease was first described in 1932 by three doctors—Burrill Crohn, Leon Ginzberg, and Gordon D. Oppenheimer 2. At the time, any disease in the small intestine was thought to be intestinal tuberculosis. These doctors collected data from 14 patients with symptoms of abdominal cramps, diarrhea, fever, and weight loss, which showed that the symptoms were not the result of tuberculosis or any other known disease. They described a new disease entity, which was first called regional ileitis, and later, Crohn’s disease 3.

The clinical presentation of ileitis may vary from an acute and self-limited form of right lower quadrant pain and/or diarrhea, as in the majority of cases of bacterial ileitis, but some conditions (i.e., vasculitis or Mycobacterium tuberculosis) follow a chronic and debilitating course complicated by obstructive symptoms, hemorrhage, and/or extraintestinal manifestations. Ileitis associated with spondylarthropathy or nonsteroidal anti-inflammatory drugs (NSAIDs) is typically subclinical and often escapes detection unless further testing is warranted by symptoms 1. In a minority of patients with long-standing Crohn’s ileitis, the recrudescence of symptoms may represent a neoplasm involving the ileum. Distinguishing between the various forms of ileitis remains a test of clinical acumen. The diagnosis of the specific etiology is suggested by a detailed history and physical examination, laboratory testing, and ileocolonoscopy and/or radiologic data.

Diagnosis of the exact cause of ileitis is critical to timely treatment and the treatment plan decided by your doctor. Your doctor will review your medical history and perform a thorough physical examination. A series of tests may also be ordered to confirm the diagnosis which may include stool analysis, X-rays, barium X-rays of the small intestine, CT scan, colonoscopy (narrow lighted tube is inserted into the anus for a close examination) and biopsy.

Based on the results of the diagnostic tests, ileitis may be treated with medications including antibiotics, corticosteroids, anti-inflammatories, antidiarrheal and immune-suppressing medications, as well as dietary supplements to reduce inflammation and manage associated symptoms. Surgery is indicated if symptoms are not controlled with medications or complications develop. Surgery is performed to remove the diseased part, correct blockages, intestinal bleeding and perforations in the intestine. You need to maintain a healthy lifestyle, exercise regularly, eat well and avoid smoking.

Ileitis causes

Ileitis, defined as inflammation of the ileum, is classically caused by Crohn’s disease. However, a wide variety of diseases may be associated with ileitis. These include infectious diseases, spondyloarthropathies, vasculitides, ischemia, neoplasms, drug-related, eosinophilic enteritis, sarcoidosis, amyloidosis, and a variety of other conditions. The diagnosis of the specific cause of ileitis is of paramount importance because misdiagnosis may result in delays or errors in patient management. This review describes each of these entities and provides a concise description of the differentiating characteristics from those of Crohn’s disease.

Selected causes of ileitis 1:

Infectious

  • Yersinia spp.
  • Salmonella spp.
  • Clostridium difficile
  • Typhlitis
  • Mycobacterium tuberculosis
  • Mycobacterium avium
  • Actinomycosis
  • Anisakiasis
  • Cytomegalovirus
  • Histoplasma capsulatum

Spondyloarthropathies

  • Ankylosing spondylitis
  • Reactive arthritis
  • Arthritis associated with inflammatory bowel disease
  • Psoriasis with arthritis
  • Undifferentiated spondylarthropathy

Vascular

  • Vasculitides
    • Systemic lupus erythematosus
    • Polyarteritis nodosa
    • Henoch-Schönlein purpura
    • Behçet’s disease
    • Other vasculitides: Churg-Strauss syndrome, rheumatoid arthritis vasculitis,
    • Wegener granulomatosis, lymphomatoid granulomatosis, giant-cell arteritis, Takayasu arteritis, thromboangiitis obliterans
  • Ischemia

Small-bowel neoplasms

  • Cecal or small-bowel (ileal) adenocarcinoma
  • Lymphoma
  • Carcinoid tumor
  • Lymphosarcoma
  • Metastatic cancer

Drug-related

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) enteropathy
  • Other drugs: potassium chloride tablets, parenteral gold therapy, oral contraceptives, ergotamine, digoxin, diuretics, antihypertensives

Infiltrative

  • Eosinophilic enteritis
  • Sarcoidosis
  • Amyloidosis

Other causes

  • Backwash ileitis due to ulcerative colitis
  • Endometriosis
  • Radiation enteritis

Table 1. Summary of the conditions related to the development of terminal ileitis

ClassificationCondition
Inflammatory bowel diseaseCrohn’s disease
Ulcerative colitis (backwash ileitis)
Anatomic alterationMeckel’s diverticulum
Drug intakeNon-steroidal anti-inflammatory
Antihypertensives
Digoxin
Diuretics
Ergotamine
Oral contraceptives
Vascular conditionsIschemia
Behcet’s disease
Giant-cell arteritis
Henoch-Schonlein purpura
Lymphomatoid granulomatosis
Polyarteritis nodosa
Systemic lupus erythematosus
Wegener granulomatosis
Intestinal infectionActinomycosis
Anisakiasis
Clostridium difficile
Cryptococcus neoformans
Cytomegalovirus
Mycobacterium tuberculosis
Neutropenic enterocolitis
Salmonella spp.
Yersinia enterocolitica and Y. pseudotuberculosis
SpondyloarthropathiesAnkylosing spondylitis
Arthritis associated with inflammatory bowel disease
Psoriasis with arthritis
Reactive arthritis
Undifferentiated spondylarthropathy
Malignant diseasesCarcinoid tumor
Cecal adenocarcinoma
Ileal adenocarcinoma
Lymphoma
Lymphosarcoma
Metastatic cancer
InfiltrativeAmyloidosis
Eosinophilic enteritis
Sarcoidosis
[Source 4 ]

Types of ileitis

Inflammatory bowel disease (IBD)

Crohn’s disease and ulcerative colitis are polygenic autoimmune diseases with multifactorial etiology sharing similar peculiarities as risk factors, clinical, endoscopic and histological patterns, and genetic predisposition. The manifestations are systemic and may lead to a serious damage to the gastrointestinal tract, and extra-intestinal manifestations. On the other hand, in ulcerative colitis inflammation pattern is normally restricted to the mucosal surface, starting in the rectum and extending in a uniform pattern throughout the colon and rarely affecting the terminal ileum 5.

Crohn’s disease

The inflammation of the ileum is often caused by Crohn’s disease that manifests due to an idiopathic transmural inflammation affecting all the wall layers and may occur from mouth to anus but the most common affected site is the distal ileum. Skipped areas of inflammation can be found and this process leads to formation of ulcers that may produce penetrating (fistulizing), fibrostenotic (stricturing), or inflammatory pattern in the perianal region and abdominal wall 6.

This disorder was described by Crohn in 1932 after studying 14 cases of terminal ileitis. Crohn’s disease patterns involve transmural inflammation, thickened submucosa, fissuring ulceration and non-caseating granulomas. It is frequently followed by a number of symptoms such as abdominal pain, diarrhea, gastrointestinal bleeding, malabsorption, and weight loss, and may lead to life-threatening complications 7.

The primary location of Crohn’s disease, in approximately two-thirds of cases, is the small intestine, specifically the terminal ileum, probably due to disruption in the immune response to environmental factors in genetically predisposed individuals and the commonly presence of erosions and ulcers is referred normally to Crohn’s disease 4. Results of Crohn’s disease biopsies show an inflammatory cellular infiltrate with crypt abscesses, architectural distortion, and occasional granulomas. Nevertheless, the exclusion of other possibilities of terminal ileitis requires the performance of a clinic, laboratory, endoscopic, and histopathological evaluation of the individuals 8.

Backwash ileitis

Backwash ileitis refers to inflammation in the distal few centimeters of terminal ileum in patients with ulcerative colitis 9. Backwash ileitis is caused by reflux of colonic contents, and when present, may raise the differential diagnosis of Crohn’s disease. In general, the severity of ileal inflammation parallels the severity of colonic activity, being more common with pancolitis and cecal involvement. Associations with an aggressive disease course, primary sclerosing cholangitis, and following subtotal colectomy for ulcerative colitis have been reported. Definite diagnostic criteria for backwash ileitis have not been determined, but it should be restricted to an active enteritis that involves the ileum in a contiguous pattern from the cecum and has a similar or greater degree of inflammation. Distinguishing Crohn’s ileocolitis and “panulcerative” colitis with backwash ileitis is otherwise straightforward when granulomas are present on “histology or aphthous ulcers, cobblestoning, and skip lesions are seen endoscopically, but can be a clinical challenge when these features are absent” 10.

Meckel’s diverticulum

Meckel’s diverticulum represents the most common congenital anomalies of the digestive tract that occurs in the gastrointestinal tract, reaching an incidence of 2-4% in the general population, although most patients are asymptomatic. This anomaly refers to the persistence of the embryological connection between the umbilical and bowel. Symptomatic cases usually course with hemorrhage, intestinal obstruction, ulceration, perforation, inflammation, intussusceptions, and malignant transformation 11.

Many studies have shown the association among Meckel’s diverticulum and Crohn disease, and some authors postulate that ileitis is attributable to acid-secreting gastric heterotopia. Complications of Meckel’s diverticulum are more frequent in male and younger individuals. Bleeding occurs more frequently in adult males and in children, mainly younger than 4 years of age, and it occurs mainly as obstruction 12.

In a recent study with 48 adult individuals, Hamilton and Arnason 13 found that some of them presented inflammatory modifications in the small intestine neighboring the diverticulum and concluded that the ileitis reaching short segment of mucosa and submucosa near Meckel’s diverticulum is common, and is not necessarily associated to Crohn disease.

Infectious ileitis

Yersinia

Yersinia enterocolitica and Yersinia pseudotuberculosis are acquired by ingestion of contaminated food (e.g., raw vegetables, milk products, and raw pork intestines [chitterlings]) or water. Less often, acquisition occurs from contact with infected wild or domestic animals. Enterocolitis is the most common clinical manifestation and is characterized by diarrhea, low-grade fever, and abdominal pain lasting 1 to 3 weeks. Vomiting occurs in 15% to 40% of cases. Severe Yersinia infections may cause ileal perforation and rectal bleeding. Other manifestations include reactive polyarthritis (especially among HLA-B27–positive patients) and septicemia with metastatic complications (especially among immunosuppressed patients or those with iron overload). Clinical illness results from the organism penetrating the mucosa and invading the underlying intestinal lymphoid tissue, particularly Peyer’s patches.

Diagnosis is by stool culture. Radiographically, a thickened and nodular mucosal pattern in the terminal ileum is seen. In contrast to Crohn’s disease, fistula formation and fibrotic stenosis are not observed. Endoscopic features of Yersinia include aphthoid lesions of the cecum and terminal ileum with round or oval elevations with ulcerations. The ulcers are mostly uniform in size and shape, in contrast to Crohn’s disease 14.

Yersinia can also lead to mesenteric adenitis with terminal ileitis mimicking acute appendicitis, which most commonly occurs in older children and adults. Presentation is right lower quadrant pain with fever, whereas diarrhea is absent or mild. Symptoms may lead to an unnecessary appendectomy; surgery discloses a normal appendix, edematous thickening of the ileum and cecum, and enlarged mesenteric lymph nodes. Sonographic or CT examination may provide clues to the diagnosis: (sub)mucosal bowel wall thickening with enlarged mesenteric lymph nodes 15. By contrast, ileocecal Crohn’s disease usually has transmural inflammation giving rise to inflamed, noncompressible fat surrounding the ileum.

Salmonella

Nontyphoidal Salmonella, the most commonly identified cause of foodborne illness in the United States, occurs after ingestion of contaminated food products of animal origin (eg, eggs, dairy products, poultry, or ground meat). Other food items (ie, unpasteurized orange juice and peanut butter) and exposure to exotic pets have also been implicated 16. Unlike nontyphoidal Salmonella, enteric fever (Salmonella typhi and Salmonella paratyphi) is transmitted person-to-person.

Salmonella infections most often cause self-limited acute gastroenteritis, but may cause bacteremia, vascular infections, and/or a chronic carrier state. Because Salmonella can affect the regional mesenteric lymph nodes, adenitis and terminal ileitis may occur, mimicking acute appendicitis. The CT findings of Salmonella ileitis include circumferential and homogenous thickening of the terminal ileum wall spanning a 10- to 15-cm segment 17. Differentiating other causes of ileitis, including Crohn’s disease, may be problematic on CT scan or endoscopy; biopsy is useful, showing acute ileitis. The definite diagnosis of Salmonella is based on culture.

Clostridium difficile

Clostridium difficile typically causes antibiotic-associated colitis. Small-bowel infections are rare, but well-described 18. Ileal Clostridium difficile infection caused by hypervirulent BI/NAP1/027 strains has been reported 19. Cases may occur after colectomy and present with low-grade fevers, abdominal or pelvic pain, and increased ileostomy output 18. Diagnosis is by visualizing pseudomembranes and/or stool studies showing toxin-producing organisms.

Typhlitis

Typhlitis is an acute, life-threatening inflammatory condition of the cecum and ascending colon that may also affect the terminal ileum. It most often occurs in patients with immunocompromising conditions. The exact pathogenesis is unknown, but probably involves damaged mucosa (from chemotherapy, radiation therapy, and/or leukemic infiltration), profound neutropenia, impaired host defenses, and possibly ischemia.

Clinically, it manifests as right lower quadrant pain, fever, nausea, vomiting, bloody diarrhea, and/or evidence of peritoneal inflammation. Early diagnosis is important, because without treatment the inflammatory process can progress rapidly to transmural necrosis with subsequent perforation.

The diagnosis is suggested by finding a thickened bowel wall involving the ileocecal region in an immunosuppressed or neutropenic patient. CT or ultrasound findings include cecal and terminal ileal wall thickening, often with decreased attenuation suggesting edema, pericolic fluid collection or fat stranding, pneumatosis coli, and intramural low-attenuation regions indicative of edema or necrosis 20. The degree of bowel wall thickening typically correlates with the severity of disease 21. Endoscopy during pancytopenia is usually contraindicated. Histologic examination of surgically removed bowel shows mononuclear infiltrates and a variety of bacteria and fungi invading the affected bowel wall.

Mycobacterium tuberculosis

Extrapulmonary tuberculosis accounts for about 20% of cases in immunocompetent patients and 50% of cases in HIV-positive individuals; intestinal tuberculosis is the sixth most prevalent form of extrapulmonary tuberculosis. Bovine TB (Mycobacterium bovis), caused by contaminated dairy products, is a rare cause of intestinal tuberculosis that exists where pasteurization practices are lacking.

Intestinal tuberculosis develops most commonly after ingesting infected sputum in cases of active pulmonary TB. Prior to effective therapy, up to 70% of tuberculosis cases developed intestinal tuberculosis via this route. Other routes include hematogenous spread or contiguous spread from adjacent organs. The ileocecal area and jejunoileum are the most common sites involved because of high densities of lymphoid aggregates and physiologic stasis. In studies, the ileocecal region has been involved in about 90% of intestinal tuberculosis cases 22.

Intestinal tuberculosis is thought to arise by the same pathophysiologic sequence as pulmonary TB; initial infection of macrophages followed by multiplication, subsequent caseation necrosis, and host inflammatory response. The intestinal lesions can be ulcerative (most common), hypertrophic or ulcerohypertrophic, or fibrous. With chronic inflammation, the ileal wall may become stenotic or fibrotic with stricture formation or may form masses (tuberculomas) leading to intestinal obstruction or perforation. Rarely, intestinal tuberculosis presents with malabsorption and a protein-losing enteropathy.

Symptoms include fever, night sweats, abdominal pain, a palpable mass, altered bowel habits, and/or bleeding 23. Because symptoms are nonspecific and about 70% of intestinal tuberculosis cases have a normal chest radiograph, clinicians must have a high suspicion for diagnosis. Several disease processes, as described in this review, resemble TB ileitis. A notoriously difficult dilemma is to differentiate intestinal tuberculosis from Crohn’s disease, especially in geographic regions where both diseases are prevalent. Features that favor intestinal tuberculosis are high fevers in the absence of an intra-abdominal abscess, lack of perianal disease, and shorter duration of symptoms 24. Serologic tests such as anti–Saccharomyces cerevisiae antibodies (ASCA) do not reliably discriminate between intestinal tuberculosis and Crohn’s disease 25.

Contrast-enhanced CT, MRI, and ultrasound may aid in differentiating intestinal tuberculosis from Crohn’s disease. Findings supportive of intestinal tuberculosis in the ileocecal region include asymmetric wall thickening and enlarged necrotic lymph nodes 26. In Crohn’s disease, wall thickening is usually symmetric and concentric, with fibrofatty proliferation of the mesentery known as “creeping fat.”

Endoscopic features of intestinal tuberculosis are similar to Crohn’s disease; both may have ulcerations, pseudopolyps, luminal narrowing, strictures, and nodularity of the ileocecal valve 27. As in Crohn’s disease, intestinal tuberculosis may involve any part of the gastrointestinal (gastrointestinal) tract but the esophagus, stomach, rectosigmoid, and anal canal are much less commonly affected. In a recent study, clinical parameters more common in Crohn’s disease were anorectal lesions, longitudinal ulcers, aphthous ulcers, and a cobblestone appearance that involved fewer than four segments; a patulous ileocecal valve, transverse ulcers, and pseudopolyps were observed more frequently in patients with intestinal tuberculosis 28.

It can be challenging to diagnose intestinal tuberculosis on endoscopic biopsy. The typical caseating granulomas and acid-fast bacilli (AFB) stained by Ziehl-Neelsen are present in less than 30% of cases. PCR may provide a rapid diagnosis, but endoscopic biopsy material has sensitivities of only 40% to 75% 29. A positive TB culture remains the gold standard, but diagnosis may be delayed (3–8 weeks). Apart from finding AFB, differentiating intestinal tuberculosis and Crohn’s disease can be difficult. Histologic features encountered more frequently in intestinal tuberculosis are granulomas that are confluent, larger (> 200 µm), and multiple in number (> 5 per section) 30.

Mycobacterium avium-intracellulare complex

Disseminated Mycobacterium avium-intracellulare complex (MAC) occurs predominantly in persons with AIDS or immunosuppressing conditions. The bacteria are acquired by ingestion or inhalation with intestinal localization as a consequence of direct inoculation, shedding from the lungs, or hematogenous spread. The main symptoms (diarrhea, malabsorption, and fever) resemble Whipple’s clinically 31. MAC infections are also called pseudo-Whipple disease because of diffuse mucosal fold thickening in the jejunum and histiocytic aggregates that stain positive with periodic acid–Schiff (PAS).

MAC also mimics Crohn’s disease with terminal ileitis. Distinguishing features of mycobacterium avium-intracellulare complex (MAC) are diffuse granulomatous involvement of the terminal ileum, positive stain and culture for MAC, and response to antimycobacterial therapy. Barium examination often demonstrates a separation of small bowel segments caused by mesenteric lymphadenopathy. In terms of deciphering Mycobacterium tuberculosis and mycobacterium avium-intracellulare complex (MAC) infections radiographically, diffuse jejunal wall thickening and enlarged soft-tissue attenuating lymph nodes with hepatosplenomegaly suggest disseminated mycobacterium avium-intracellulare complex infection, whereas focal abdominal lesions with low-attenuating lymph nodes suggest M. tuberculosis 32.

Diagnosis is suggested by the clinical and radiographic features discussed previously. Isolation of mycobacterium avium-intracellulare complex from the blood or another sterile site (eg, lymph node, bone marrow, liver, spleen) establishes the diagnosis. Mycobacterium avium-intracellulare complex in the stool alone does not make the diagnosis because it may be a colonizer.

Actinomycosis

Actinomycosis is a chronic bacterial infection caused by a heterogenous group of anaerobic gram-positive bacteria. It is characterized by contiguous spread, suppurative and granulomatous inflammation, and formation of multiple abscesses and fistulous sinus tracts that may discharge sulfur granules. The three main clinical forms of this disease are cervicofacial, thoracic, and abdominopelvic, with the abdominopelvic form accounting for 10% to 20% of cases.

Because the bacteria are normal microflora of the gastrointestinal tract and are not virulent, injury (from trauma, surgery, or foreign body ingestion) to the mucosa is required to cause disease. The ileocecal region is most commonly involved, perhaps because of physiologic stasis. Symptoms follow an indolent course with right lower abdominal pain, mass, and/or fever. Contrast-enhanced CT imaging reveals an infiltrative mass invading surrounding tissues with focal areas of decreased attenuation 33. Lymphadenopathy is uncommon. Because symptoms and signs are nonspecific, the diagnosis is usually delayed with only 10% of cases diagnosed preoperatively 34.

Anisakiasis

Gastrointestinal anisakiasis is acquired after ingestion of raw marine fish or squid infested with larvae of the roundworm Anisakis simplex (herring worm) or Pseudoterranova decipiens (cod worm). Anisakiasis is most common in Japan, but also occurs in the United States. Symptoms include violent and relatively acute epigastric or abdominal pain caused by penetration of larvae through the stomach or lower small intestine mucosa, especially the ileum. Nausea, vomiting, and fever may occur. Symptoms begin within 48 hours of ingestion, and quickly self-resolve or become chronic. Chronic infection may provoke an eosinophilic granulomatous response in the ileocecal region, causing masses with obstruction, or may produce nonspecific abdominal symptoms. Cases may mimic appendicitis or regional enteritis. Barium studies show narrowing of the intestinal lumen in areas with mucosal inflammation or occasionally a filling defect, suggesting a worm. Upper endoscopy may reveal edematous mucosa with ulcerations and a thin, stringlike worm penetrating the gastric wall 35. Gastroscopic removal of worms often hastens symptom resolution.

Cytomegalovirus

Cytomegalovirus (CMV) infection of the gastrointestinal tract most frequently causes esophageal ulcers and colitis, whereas small bowel involvement occurs in only 4% of gastrointestinal cases 36. Disease usually occurs in immunosuppressed patients, including those with AIDS or transplant recipients. Of note, AIDS patients with CMV often have concurrent infections (eg, mycobacterium avium-intracellulare complex [MAC]). Symptoms include fever, abdominal pain, watery diarrhea, or bleeding. Endoscopic findings include erosions, ulceration, and mucosal hemorrhage; a mass lesion may also occur. The prototypical ulceration has a well-defined, punched-out appearance. The pathogenesis involves ischemic mucosal injury secondary to infection of the vascular endothelial cells. The diagnosis is by demonstration of typical CMV inclusion bodies by routine histologic examination, culture, staining for CMV antigen, or DNA 37.

Histoplasmosis

Histoplasma capsulatum is a dimorphic fungus that exists in mold form in soil contaminated with bird or bat droppings, and transforms to yeast form when inhaled. Infection is usually asymptomatic or results in a self-limited respiratory illness. gastrointestinal involvement occurs in 70% to 90% of those with disseminated histoplasmosis as determined by autopsy studies, and may be misdiagnosed as inflammatory bowel disease (IBD) or malignancy. Dissemination to the gastrointestinal tract occurs via the reticuloendothelial system by tissue macrophages that accumulate in lymphoid aggregates and Peyer’s patches. This likely explains why the terminal ileum is commonly affected 38. Symptoms include diarrhea, weight loss, fever, and/or abdominal pain. Patients may also have gastrointestinal bleeding, bowel perforation, or obstruction from ileocecal masses or enlarged retroperitoneal lymph nodes. Hepatomegaly and/or splenomegaly occur in 30% to 100% of cases.

Lesions on endoscopy or laparotomy range from segmental or continuous superficial mucosal ulcerations with erythema or edema, to deep ulcers with or without frank perforation 39. Intraabdominal lymphadenopathy is seen on CT in two thirds of patients. Diagnosis is by positive fungal culture or tissue biopsy showing diffuse lymphohistiocytic infiltrates in the mucosa and submucosa. Gomori methenamine or Grocott silver stains demonstrate H. capsulatum organisms, which appear as 2-µ to 4-µ round, budding yeast.

Ileitis associated with spondyloarthropathies

Spondyloarthropathies are characterized by inflammation of axial joints, asymmetric oligoarthritis, and enthesitis. Spondyloarthropathies include ankylosing spondylitis, reactive arthritis, arthritis associated with inflammatory bowel disease and psoriasis, and undifferentiated spondyloarthropathies. Spondyloarthropathies are associated with extra-articular manifestations, including uveitis and genital, skin, and inflammatory gut lesions. Inflammatory gut lesions occur in up to two thirds of patients and usually affect the terminal ileum. In most cases, however, inflammation is subclinical and escapes detection unless colonoscopic biopsy is warranted by symptoms. The histologic appearance of lesions is either acute or chronic, and is not related to disease duration. The acute form is mainly seen in patients with reactive arthritis and mimics bacterial ileitis (preserved architecture and neutrophil dominance). The chronic form is more prevalent in ankylosing spondylitis and undifferentiated Spondyloarthropathies, and may be indistinguishable from Crohn’s disease (disturbed mucosal architecture, irregular and blunted villi, distorted crypts, and lymphocyte dominant). In some cases, aphthoid ulcers and sarcoidlike granulomas are present 40.

Distinguishing ileitis of spondyloarthropathies and Crohn’s disease can be difficult. The main distinctions are that Spondyloarthropathies does not usually cause radiologically detectable abnormalities of the terminal ileum and most patients have asymptomatic gut inflammation. HLA-B27 testing may be helpful and is positive in more than 80% of cases of ankylosing spondylitis versus 10% to 35% of Crohn’s disease patients. In most cases of Crohn’s disease, intestinal symptoms precede or coincide with the joint manifestations. However, patients with Spondyloarthropathies typically develop gastrointestinal symptoms after the appearance of joint symptoms. Finally, the pattern of joint involvement may be a distinguishing feature.

In spondyloarthropathies, a relationship exists between gut and joint findings: chronic gastrointestinal lesions are associated with more advanced sacroiliitis, spondylitis, and peripheral arthritis 40. Remission of articular inflammation correlates with disappearance of gut inflammation, whereas the persistence of joint inflammation is mostly associated with the persistence of gut inflammation.

Vasculitides

Vasculitides that are primary to the intestine or occur secondary to systemic vasculitis represent a rare cause of ileitis. The most common vasculitides with gastrointestinal involvement include the medium-sized vessel vasculitides of systemic lupus erythematosus and polyarteritis nodosa, and the small vessel vasculitides of Henoch-Schönlein purpura and Behçet’s disease. Visceral vasculitis presents with abdominal pain, nausea, vomiting, diarrhea, and gastrointestinal bleeding. Small-vessel or leukocytoclastic vasculitis is characterized by mucosal ischemia, whereas vasculitis involving medium-size or larger vessels may more likely result in transmural involvement, leading to peritoneal findings or perforation. Other serious complications include obstruction, protein-losing enteropathy, and intussusception. Moreover, patients with acquired antiphospholipid antibodies and systemic lupus erythematosus or related disorders are at increased risk for mesenteric artery thrombosis and subsequent bowel infarction 41.

Among the vasculitides, Henoch-Schönlein purpura deserves mention. Henoch-Schönlein purpura is an IgA-mediated vasculitis associated with palpable purpura predominantly on the lower extremities and buttocks accompanied by arthralgias, abdominal pain, and occasionally nephritis. Henoch-Schönlein purpura is rare in adults as compared to children (90% of patients are < 10 years old). Common gastrointestinal presentations are colicky right lower quadrant pain and gastrointestinal bleeding. In 10% to 15% of patients, gastrointestinal symptoms precede cutaneous lesions by ≥ 4 weeks. Induction of IgA in the abundant Peyer patches may be involved in the pathogenesis of ileitis and subsequent spread to other involved sites (skin and kidney) because of antigen mimicry. The endoscopic findings in the ileum may be dramatic, with marked mucosal congestion, hemorrhagic necrosis, and ulceration consistent with ischemia 42. Classic IgA deposition and leukocytoclastic vasculitis in cutaneous, renal, or bowel tissue confirms the diagnosis. As for Crohn’s disease, in a small number of cases, cutaneous leukocytoclastic vasculitis has been reported; however, the skin manifestations are most commonly erythema nodosum and pyoderma gangrenosum.

Diagnosing vasculitis is typically based on evidence of generalized disease activity elsewhere. For example, although mucocutaneous manifestations are common in Crohn’s disease, the recurrent and severe aphthous stomatitis and genital ulcers observed in Behçet’s are a notable feature of this form of vasculitis. Plain radiographic studies may reveal nondiagnostic findings such as segmental bowel dilation, air-fluid levels, “thumbprinting” or narrowing of the lumen, and pseudoobstruction. Contrast-enhanced CT may show engorgement of mesenteric vessels (comb sign), multisegmental areas of symmetric bowel thickening (> 3 mm), abnormal bowel-wall enhancement (a double halo or target sign), and ascites 43. These findings are also seen in Crohn’s disease; however, the presence of creeping fat of the mesentery, small mesenteric lymph nodes, and complications of Crohn’s disease, including abscess, fistula, and/or perianal disease, are differentiating features.

Ischemia

Other conditions aside from vasculitis cause ischemic ileitis. An important cause is nonocclusive mesenteric ischemia (nonocclusive mesenteric ischemia) as a result of splanchnic hypoperfusion and vasospasm observed predominantly in elderly patients with atherosclerotic vascular disease in the setting of low-flow states (eg, shock, heart failure, drugs such as cocaine). The microvasculature is patent in nonocclusive mesenteric ischemia, but blood flow is inadequate to meet intestinal tissue demands. Because the ileocolic branches are the longest branches of the superior mesenteric artery, the ileocecal region is most susceptible to ischemia from poor perfusion 44.

Early diagnosis is difficult because of the nonspecific symptoms (abdominal pain, nausea, vomiting, and ileus). Contrast-enhanced CT reveals patent mesenteric vessels and bowel wall thickening. Ileocolonoscopy reveals segmental distribution with a clear boundary between the injured and uninvolved region. Lesions range from marked edematous mucosa with loss of clear vascular vessel pattern or having a dusky pattern to scattered discrete ulcerations and friability 44.

Small-bowel neoplasms

The mucosa of the small intestine encompasses about 90% of the luminal surface area of the digestive system, but accounts for only 2% of gastrointestinal malignant neoplasms. Neoplastic processes with a propensity for the ileum are adenocarcinoma, lymphoma, and carcinoid tumor. Small-bowel neoplasms may occur sporadically, in association with genetic diseases (familial adenomatous polyposis coli, hereditary nonpolyposis colorectal cancer, or Peutz–Jeghers syndrome), or in association with chronic intestinal inflammatory disorders (Crohn’s disease or celiac sprue).

The diagnosis is often made late because of their uncommon occurrence and nonspecific symptoms. The CT appearance of ileal adenocarcinoma is an annular and constricting lesion involving a short segment of bowel. For patients with carcinoid, CT reveals an ill-defined spiculated mass with a stellate pattern containing calcification. Lymphoma most commonly manifests as single or multiple segmental areas of markedly thickened (1.5–7 cm) circumferential thickening, or may ulcerate with formation of a fistulous tract to adjacent bowel loops, mimicking Crohn’s disease 45.

The risk of gastrointestinal cancer is elevated in patients with inflammatory bowel disease (eg, 60-fold higher compared to the general population). Small-bowel adenocarcinoma complicating Crohn’s disease is predominantly seen in men, in patients with excluded bowel loops, and at the distal ileum in an area of active disease 46. Carcinoid tumors have also been described in association with Crohn’s disease, and these cases tend to be malignant and have a worse prognosis 47. Ileal carcinoid tumor should be suspected in elderly Crohn’s disease patients presenting with obstructive symptoms. In general, the presence of suspected ileal Crohn’s disease refractory to medical therapy should alert clinicians to the possibility of a small-bowel neoplasm. When technically feasible, ileoscopy with biopsy may help distinguish between the two and guide early diagnosis and treatment.

Drug-related ileitis

Nonsteroidal anti-inflammatory drugs

Although the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in the stomach and duodenum are well established, only recently were NSAIDs shown to cause small-bowel injury (NSAID enteropathy). An autopsy study detected small-intestine ulcers in 8.4% and mucosal breaks in 55% of patients who recently used NSAIDs compared to 0.6% and 7%, respectively, in nonusers 48. In a video capsule endoscopy (VCE) study, 71% of long-term NSAID users had jejunal or ileal mucosal injury 49. Virtually all classes of NSAIDs that block both cyclooxygenase (COX)-1 and COX-2 have been implicated. Whether COX-2–selective inhibitors cause similar effects is unclear. In an attempt to decrease gastroduodenal side effects of NSAIDs, the use of extended-release or enteric-coated formulations may have shifted the damage to the distal small intestine and colon. Hold-up of pills at the ileocecal valve, partially because of the inhibition of prostaglandin that suppresses normal propagation, may lead to ileitis.

The pathogenesis involves a combination of biochemical events that compromise enterocyte integrity and increase intestinal permeability. These include COX-1 inhibition (restricts mucosal blood flow), COX-2 inhibition (through an unknown immunomodulatory mechanism), and the topical effects of NSAIDs (disrupt membrane phospholipids and uncouple mitochondrial oxidative phosphorylation). This increased permeability allows exposure to luminal substances (eg, bacteria, intraluminal toxins, bile acids), thereby leading to inflammation.

Although NSAID-related inflammation by itself rarely has clinical consequences, in some patients, it may induce erosions or ulceration, protein-losing enteropathy, or occasionally bleeding, perforation, strictures, or obstruction. A type of stricture known as “diaphragm disease” is characteristic, if not pathognomonic, for NSAID-induced damage. These diaphragms are numerous, thin-walled, concentric, septate-like mucosal projections that narrow the intestinal lumen to pinhole size. They are characterized histologically by prominent submucosal fibrosis without evidence of vascular involvement 50. The adjacent mucosa between diaphragms is usually normal. As a potential cause of subacute obstruction, these strictures are difficult to diagnose because they may appear as exaggerated plica circularis.

Several indirect diagnostic tests indicating NSAID-induced inflammation and increased permeability are available, but are nonspecific and abnormal in a variety of other conditions. However, these methods show that long-term NSAID use is associated with enhanced migration of 111-indium-labeled leucocytes, increased fecal 111-indium secretion, and increased fecal calprotectin shedding in more than 50% of patients 51. Diagnosis may also be made using direct methods such as video capsule endoscopy, ileocolonoscopy, and balloon enteroscopy. Regarding these modalities, NSAID enteropathy involving the ileum is suspected in patients with a history of NSAID use, findings of erosion, ulcer, and/or typical diaphragm-like strictures, clinical improvement in symptoms and/or endoscopic findings by cessation of NSAID use (except for diaphragm disease), and after exclusion of other causes 52. Differentiating NSAID-induced versus Crohn’s disease ileitis may be complicated by the fact that the two entities may coexist, or that NSAIDs can flare Crohn’s disease. Helpful distinguishing features are that Crohn’s disease classically causes long, thick inflammatory strictures rather than thin fibrotic diaphragms and that ulcers are often deeper, longitudinal, and more irregular than the sharply demarcated lesions of NSAID enteropathy.

Other causes of drug-related ileitis

Potassium chloride tablets are a rare cause of ileitis. In the 1960s, cases of small-intestinal ulceration were attributed to the use of enteric-coated potassium chloride 53. In 1965, this form of the drug was withdrawn from the market; the incidence was greatly diminished, but not eliminated, with the development of slow-release formulations. The clinical presentation, diagnosis, and management are identical to NSAID-induced ileitis.

Parenteral gold therapy has also been associated with enterocolitis, with edema and ulceration limited to the ileum 54. This rare complication is most commonly seen in women and can occur shortly after starting therapy for rheumatoid arthritis. Other drugs that may cause ileitis include oral contraceptives, ergotamine, digoxin, and enteric-coated hydrochlorothiazide with potassium.

Infiltrative causes of ileitis

Eosinophilic gastroenteritis

Eosinophilic gastroenteritis is a rare disorder characterized by prominent eosinophilic infiltration of the gastrointestinal tract in the absence of known causes of eosinophilia (eg, parasitic infection, malignancy, and drug reaction). eosinophilic gastroenteritis commonly involves the stomach and small intestine, but occasionally causes diffuse colonic involvement.

Although the etiology is unknown, a personal or family history of food allergies and atopic disorders is present in 50% to 70% of cases. The proposed pathogenesis is alteration in the mucosal integrity, resulting in localization of various antigens in the gut wall, thereby inducing tissue and blood eosinophilia 55.

Clinical features vary depending on the layer(s) and extent of bowel involved with eosinophilic infiltration (mucosa, muscle, and/or subserosa). Small-bowel eosinophilic gastroenteritis may present with abdominal pain, diarrhea, or malabsorption. Ileal strictures and bowel obstruction may occur with muscle layer involvement, and eosinophilic ascites manifests if the serosa is affected. Patients may have peripheral eosinophilia or elevated serum IgE levels.

Radiographic changes are variable, but may show bowel wall thickening, obstruction, or ascites. Definitive diagnosis requires histologic confirmation of eosinophilic infiltration in tissue obtained on endoscopy or surgery. The endoscopic findings vary from normal mucosa to mild erythema, nodularity, and frank ulceration. Diffuse enteritis with complete loss of villi, submucosal edema, and fibrosis may be present. Multiple biopsies are required because of the patchy nature of the disease, and full-thickness surgical biopsies may be necessary if disease is confined to the muscle layer 55. Crohn’s disease can usually be differentiated by the typical architectural distortion that is not found in eosinophilic gastroenteritis. Rarely, Crohn’s disease is associated with peripheral eosinophilia and/or an eosinophil-rich tissue infiltrate 56.

Sarcoidosis

Sarcoidosis is a chronic, multisystemic, granulomatous disease most commonly involving the lung, lymph nodes, spleen, and skin. Clinically recognizable gastrointestinal involvement occurs in 0.1% to 0.9% of patients, although the incidence of subclinical disease may be higher. The stomach is the most common portion of the gastrointestinal tract involved, whereas the small bowel is the least common. About 50% of the cases of small-bowel disease occur in the context of generalized disease, with symptoms of nonbloody diarrhea and colicky abdominal pain. Weight loss, anorexia, low-grade fever, and weakness may be present 57. In patients with sarcoidosis and suspected ileitis, ileocolonoscopy with biopsy revealing noncaseating granulomas containing multinucleated giant cells is nearly diagnostic. Proper interpretation of ileal biopsies is crucial because mycobacterial infections, histoplasmosis, Crohn’s disease, and lymphoma are granulomatous conditions that mimic sarcoidosis.

Amyloidosis

Amyloidosis is characterized by the extracellular deposition of protein in an abnormal fibrillar form. Several different types of amyloidosis exist, each defined by the identity of their respective fibril precursor protein. The three main types are primary, secondary, and dialysis-related amyloidosis. Primary amyloidosis is associated with plasma cell dyscrasias, and secondary amyloidosis is associated with inflammatory, infectious, and neoplastic diseases. Amyloid deposition in the gastrointestinal tract is greatest in the small bowel and results from either mucosal or neuromuscular infiltration. Most patients have subclinical disease; bleeding (from vascular friability or mucosal lesions), intestinal dysmotility, malabsorption (related to mucosal infiltration or bacterial overgrowth), or protein-losing enteropathy may occur 58. Endoscopic findings include a fine granular appearance, polypoid protrusions, erosions, ulcerations, mucosal friability, and thickening of the wall. Rarely, tumor-forming deposits called amyloidoma localized to the small intestine are found, mimicking adenocarcinoma. Biopsies of the affected organ, fat, or rectum reveal amyloid deposits that stain with Congo red, producing a pathognomonic red-green birefringence under cross-polarized light microscopy.

Endometriosis

Endometriosis is defined by the presence of endometrium outside the uterus, and most commonly involves nulliparous women 25 to 45 years of age. Disease occurs from retrograde menstruation of endometrial tissue implanted on the serosa of abdominal organs (implantation theory) and/or by transformation of pluripotential peritoneal mesothelium (coelomic metaplasia theory). Although the rectosigmoid colon is the most common site (85% of cases), the ileum is involved in 1% to 7% of patients 59. Ileal endometriosis presents most commonly with intermittent obstruction, constipation, or vague abdominal and/or pelvic pain. In some individuals, the predominant complaints of right lower quadrant pain, diarrhea, and/or fever may mimic Crohn’s disease. Endometriotic tissue in the ileum may undergo cyclic hormonal changes, with periodic hemorrhage. When the muscularis propria is involved, there is marked muscular hypertrophy and a fibrotic reaction in bowel wall, leading to an appearance of an extrinsic mass effect or segmental narrowing. On tissue biopsy, if only the mucosa is sampled, the typical lesions in the muscularis propria may be missed. In this regard, radiographic imaging can be helpful. In indeterminate cases, diagnostic laparoscopy is recommended 60.

Ileitis symptoms

Ileitis may present acutely with right lower quadrant pain and/or diarrhea, or with chronic obstructive symptoms and bleeding 4. Although Crohn’s disease often is the cause of ileitis, many conditions can involve the ileum, including infections localizing in the distal ileum due to the presence of Peyer’s patches and physiologic stasis. Beyond infections, systemic disorders including spondyloarthropathies, vasculitides, ischemia, and amyloidosis as well as medications may lead to ileal inflammation.

In some people with Crohn’s disease, only the last segment of the small intestine (ileum) is affected. In others, the disease is confined to the colon (part of the large intestine). The most common areas affected by Crohn’s disease are the last part of the small intestine and the colon.

Crohn’s disease symptoms depend on the part of the digestive tract involved. Signs and symptoms of Crohn’s disease can range from mild to severe and can come and go, with periods of flare-ups. They usually develop gradually, but sometimes will come on suddenly, without warning. You may also have periods of time when you have no signs or symptoms (remission).

When Crohn disease is active, signs and symptoms may include:

  • Abdominal pain and cramping.
  • Fever.
  • Fatigue.
  • Loss of appetite and weight loss.
  • Feeling that you need to pass stools, even though your bowels are already empty. It may involve straining, pain, and cramping.
  • Watery diarrhea, which may be bloody.

Other symptoms of Crohn’s disease may include:

  • Constipation
  • Sores or swelling in the eyes
  • Draining of pus, mucus, or stools from around the rectum or anus (caused by something called a fistula [inflammation from a tunnel into the skin])
  • Joint pain and swelling
  • Mouth ulcers
  • Rectal bleeding and bloody stools
  • Swollen gums
  • Tender, red bumps (nodules) under the skin, which may turn into skin ulcers

People with severe Crohn’s disease also may experience:

  • Inflammation of skin, eyes and joints
  • Inflammation of the liver or bile ducts
  • Delayed growth or sexual development, in children

The diagnosis of the cause of ileitis is of paramount importance because misdiagnosis may result in critical delays or errors in management. The specific diagnosis is suggested by the clinical disease course, presence of other systemic manifestations, appearance of imaging and endoscopic findings, and histologic results.

Crohn’s disease complications

Crohn’s disease may lead to one or more of the following complications:

  • Bowel obstruction. Crohn’s disease affects the thickness of the intestinal wall. Over time, parts of the bowel can scar and narrow, which may block the flow of digestive contents. You may require surgery to remove the diseased portion of your bowel.
  • Ulcers. Chronic inflammation can lead to open sores (ulcers) anywhere in your digestive tract, including your mouth and anus, and in the genital area (perineum).
  • Fistulas. Sometimes ulcers can extend completely through the intestinal wall, creating a fistula — an abnormal connection between different body parts. Fistulas can develop between your intestine and skin, or between your intestine and another organ. Fistulas near or around the anal area (perianal) are the most common kind. When fistulas develop in the abdomen, food may bypass areas of the bowel that are necessary for absorption. Fistulas may occur between loops of bowel, into the bladder or vagina, or out through the skin, causing continuous drainage of bowel contents to your skin. In some cases, a fistula may become infected and form an abscess, which can be life-threatening if not treated.
  • Anal fissure. This is a small tear in the tissue that lines the anus or in the skin around the anus where infections can occur. It’s often associated with painful bowel movements and may lead to a perianal fistula.
  • Malnutrition. Diarrhea, abdominal pain and cramping may make it difficult for you to eat or for your intestine to absorb enough nutrients to keep you nourished. It’s also common to develop anemia due to low iron or vitamin B-12 caused by the disease.
  • Colon cancer. Having Crohn’s disease that affects your colon increases your risk of colon cancer. General colon cancer screening guidelines for people without Crohn’s disease call for a colonoscopy every 10 years beginning at age 50. Ask your doctor whether you need to have this test done sooner and more frequently.
  • Other health problems. Crohn’s disease can cause problems in other parts of the body. Among these problems are anemia, skin disorders, osteoporosis, arthritis, and gallbladder or liver disease.
  • Medication risks. Certain Crohn’s disease drugs that act by blocking functions of the immune system are associated with a small risk of developing cancers such as lymphoma and skin cancers. They also increase risk of infection. Corticosteroids can be associated with a risk of osteoporosis, bone fractures, cataracts, glaucoma, diabetes and high blood pressure, among others. Work with your doctor to determine risks and benefits of medications.

Ileitis diagnosis

Your doctor will likely diagnose Crohn’s disease only after ruling out other possible causes for your signs and symptoms. There is no one test to diagnose Crohn’s disease.

Your doctor will likely use a combination of tests to help confirm a diagnosis of ileitis, including:

Blood tests

  • Tests for anemia or infection. Your doctor may suggest blood tests to check for anemia — a condition in which there aren’t enough red blood cells to carry adequate oxygen to your tissues — or to check for signs of infection. Expert guidelines do not currently recommend antibody or genetic testing for Crohn’s disease.
  • Fecal occult blood test. You may need to provide a stool sample so that your doctor can test for hidden (occult) blood in your stool.

Procedures

  • Colonoscopy. This test allows your doctor to view your entire colon and the very end of your ileum (terminal ileum) using a thin, flexible, lighted tube with an attached camera. During the procedure, your doctor can also take small samples of tissue (biopsy) for laboratory analysis, which may help confirm a diagnosis. Clusters of inflammatory cells called granulomas, if present, help confirm the diagnosis of Crohn’s.
  • Computerized tomography (CT). You may have a CT scan — a special X-ray technique that provides more detail than a standard X-ray does. This test looks at the entire bowel as well as at tissues outside the bowel. CT enterography is a special CT scan that provides better images of the small bowel. This test has replaced barium X-rays in many medical centers.
  • Magnetic resonance imaging (MRI). An MRI scanner uses a magnetic field and radio waves to create detailed images of organs and tissues. MRI is particularly useful for evaluating a fistula around the anal area (pelvic MRI) or the small intestine (MR enterography).
  • Capsule endoscopy. For this test, you swallow a capsule that has a camera in it. The camera takes pictures of your small intestine, which are transmitted to a recorder you wear on your belt. The images are then downloaded to a computer, displayed on a monitor and checked for signs of Crohn’s disease. The camera exits your body painlessly in your stool. You may still need endoscopy with biopsy to confirm the diagnosis of Crohn’s disease.
  • Balloon-assisted enteroscopy. For this test, a scope is used in conjunction with a device called an overtube. This enables the doctor to look further into the small bowel where standard endoscopes don’t reach. This technique is useful when capsule endoscopy shows abnormalities, but the diagnosis is still in question.

Ileitis treatment

Terminal ileitis treatment depends on the underlying cause of ileitis.

There is currently no cure for Crohn’s disease, and there is no one treatment that works for everyone. The goal of medical treatment is to reduce the inflammation that triggers your signs and symptoms. It is also to improve long-term prognosis by limiting complications. In the best cases, this may lead not only to symptom relief but also to long-term remission.

Anti-inflammatory drugs

Anti-inflammatory drugs are often the first step in the treatment of inflammatory bowel disease. They include:

  • Corticosteroids. Corticosteroids such as prednisone and budesonide (Entocort EC) can help reduce inflammation in your body, but they don’t work for everyone with Crohn’s disease. Doctors generally use them only if you don’t respond to other treatments. Corticosteroids may be used for short-term (three to four months) symptom improvement and to induce remission. Corticosteroids may also be used in combination with an immune system suppressor.
  • Oral 5-aminosalicylates. These drugs include sulfasalazine (Azulfidine), which contains sulfa, and mesalamine (Asacol HD, Delzicol, others). Oral 5-aminosalicylates have been widely used in the past but now are generally considered of limited benefit.

Immune system suppressors

These drugs also reduce inflammation, but they target your immune system, which produces the substances that cause inflammation. For some people, a combination of these drugs works better than one drug alone. Immunosuppressant drugs include:

  • Azathioprine (Azasan, Imuran) and mercaptopurine (Purinethol, Purixan). These are the most widely used immunosuppressants for treatment of inflammatory bowel disease. Taking them requires that you follow up closely with your doctor and have your blood checked regularly to look for side effects, such as a lowered resistance to infection and inflammation of the liver. They may also cause nausea and vomiting.
  • Infliximab (Remicade), adalimumab (Humira) and certolizumab pegol (Cimzia). These drugs, called TNF inhibitors or biologics, work by neutralizing an immune system protein known as tumor necrosis factor (TNF).
  • Methotrexate (Trexall). This drug is sometimes used for people with Crohn’s disease who don’t respond well to other medications. You will need to be followed closely for side effects.
  • Natalizumab (Tysabri) and vedolizumab (Entyvio). These drugs work by stopping certain immune cell molecules — integrins — from binding to other cells in your intestinal lining. Because natalizumab is associated with a rare but serious risk of progressive multifocal leukoencephalopathy — a brain disease that usually leads to death or severe disability — you must be enrolled in a special restricted distribution program to use it. Vedolizumab recently was approved for Crohn’s disease. It works like natalizumab but appears not to carry a risk of brain disease.
  • Ustekinumab (Stelara). This drug is used to treat psoriasis. Studies have shown that it’s useful in treating Crohn’s disease as well and may be used when other medical treatments fail.

Antibiotics

Antibiotics can reduce the amount of drainage and sometimes heal fistulas and abscesses in people with Crohn’s disease. Some researchers also think antibiotics help reduce harmful intestinal bacteria that may play a role in activating the intestinal immune system, leading to inflammation. Frequently prescribed antibiotics include ciprofloxacin (Cipro) and metronidazole (Flagyl).

Other medications

In addition to controlling inflammation, some medications may help relieve your signs and symptoms, but always talk to your doctor before taking any over-the-counter medications. Depending on the severity of your Crohn’s disease, your doctor may recommend one or more of the following:

  • Anti-diarrheals. A fiber supplement, such as psyllium powder (Metamucil) or methylcellulose (Citrucel), can help relieve mild to moderate diarrhea by adding bulk to your stool. For more severe diarrhea, loperamide (Imodium A-D) may be effective.
  • Pain relievers. For mild pain, your doctor may recommend acetaminophen (Tylenol, others) — but not other common pain relievers, such as ibuprofen (Advil, Motrin IB, others), naproxen sodium (Aleve). These drugs are likely to make your symptoms worse, and can make your disease worse as well.
  • Iron supplements. If you have chronic intestinal bleeding, you may develop iron deficiency anemia and need to take iron supplements.
  • Vitamin B-12 shots. Crohn’s disease can cause vitamin B-12 deficiency. Vitamin B-12 helps prevent anemia, promotes normal growth and development, and is essential for proper nerve function.
  • Calcium and vitamin D supplements. Crohn’s disease and steroids used to treat it can increase your risk of osteoporosis, so you may need to take a calcium supplement with added vitamin D.

Nutrition therapy

Your doctor may recommend a special diet given via a feeding tube (enteral nutrition) or nutrients injected into a vein (parenteral nutrition) to treat your Crohn’s disease. This can improve your overall nutrition and allow the bowel to rest. Bowel rest can reduce inflammation in the short term.

Your doctor may use nutrition therapy short term and combine it with medications, such as immune system suppressors. Enteral and parenteral nutrition are typically used to get people healthier prior to surgery or when other medications fail to control symptoms.

Your doctor may also recommend a low residue or low-fiber diet to reduce the risk of intestinal blockage if you have a narrowed bowel (stricture). A low residue diet is designed to reduce the size and number of your stools.

Surgery

If diet and lifestyle changes, drug therapy, or other treatments don’t relieve your signs and symptoms, your doctor may recommend surgery. Nearly half of those with Crohn’s disease will require at least one surgery. However, surgery does not cure Crohn’s disease.

During surgery, your surgeon removes a damaged portion of your digestive tract and then reconnects the healthy sections. Surgery may also be used to close fistulas and drain abscesses.

The benefits of surgery for Crohn’s disease are usually temporary. The disease often recurs, frequently near the reconnected tissue. The best approach is to follow surgery with medication to minimize the risk of recurrence.

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