What are the causes of ileitis involving the ileocecal valve?

Causes of Ileitis Involving the Ileocecal Valve

Ileitis of the ileocecal valve has multiple etiologies, with Crohn's disease being the most common inflammatory cause (approximately 14% of cases), followed by infectious enteritis (25%), medication-induced injury (particularly NSAIDs), backwash ileitis in ulcerative colitis, intestinal tuberculosis in endemic areas, ischemia, vasculitis, and idiopathic terminal ileitis. 1, 2, 3

Inflammatory Bowel Disease Causes

Crohn's Disease

• Crohn's disease is the primary inflammatory cause of ileocecal valve involvement, characterized by discrete ulcers, strictures of the terminal ileum or ileocecal valve, and asymmetric involvement especially along the mesenteric border. 1, 4
• Endoscopic features favoring Crohn's disease include anorectal lesions, longitudinal and aphthous ulcers, cobblestone appearance, and absence of pancolitis. 1
• Median terminal ileum wall thickness is significantly greater in Crohn's disease compared to other causes of ileitis. 5
• Ileal disease location is a risk factor for requiring surgery in Crohn's disease. 6

Backwash Ileitis in Ulcerative Colitis

• Backwash ileitis occurs in up to 20% of patients with pancolitis, characterized by mild inflammation of a few centimeters of terminal ileum without ulceration. 1
• Ileocecal valve gaping and terminal ileum dilatation are significantly more frequent in backwash ileitis, with 88.9% of patients showing pancolitis. 5
• Circumferential mural thickening (90% vs 1%) and inner-wall enhancement are more frequent in backwash ileitis than Crohn's terminal ileitis. 4
• Ileocecal valve patency indices ≥31.5% are 100% specific for distinguishing backwash ileitis from Crohn's terminal ileitis. 4
• Ileitis in ulcerative colitis patients with inactive or mild disease may represent a primary extracolonic manifestation, with 22% prevalence compared to 4% in controls. 7

Infectious Causes

Bacterial Infections

• Infectious enteritis accounts for approximately 25% of proximal jejunal and ileal wall-thickening cases. 3
• Salmonella, Shigella, and Campylobacter species have endoscopic features similar to ulcerative colitis, while Yersinia resembles Crohn's disease. 1
• Intestinal tuberculosis shows characteristic features including localized involvement, patulous ileocecal valve, transverse ulcers, and scar or pseudopolyp formation, with a positive predictive value of 88.9%. 1
• Acute gastroenteritis is the most common identifiable etiologic cause of acute terminal ileitis in children. 8

Viral and Opportunistic Infections

• Cytomegalovirus (CMV) enterocolitis can cause variable colonoscopic findings ranging from patchy erythema and micro-erosions to deep ulcers and pseudotumors. 1
• Clostridium difficile superinfection should be considered in inflammatory bowel disease patients with worsening symptoms. 1, 9

Medication-Induced Ileitis

• Non-steroidal anti-inflammatory drug (NSAID) use is a possible risk factor for pouchitis and can cause non-specific ileitis. 10
• NSAID-associated ulcers should be considered in the differential diagnosis of ileocecal ulcerative lesions. 11
• Regular NSAID use increases the risk of developing pouchitis in patients with ileal pouches. 10

Vascular and Ischemic Causes

• Ischemic colitis can involve the ileocecal region, with endoscopic findings including sharply defined segments of involvement, petechial hemorrhages, and longitudinal ulcerations. 1
• Ischemia is among the differential diagnoses for benign ileocecal ulcerative lesions. 11
• Secondary pouchitis caused by pelvic sepsis usually causes focal inflammation and should be considered. 10

Other Inflammatory and Systemic Causes

Vasculitis and Autoimmune Conditions

• Behçet's disease can cause ileocecal ulceration. 11
• Vasculitis is a recognized cause of ileitis that may follow a chronic and debilitating course complicated by obstructive symptoms and hemorrhage. 2
• Eosinophilic enteritis can involve the terminal ileum. 2

Post-Surgical and Pouch-Related

• Pre-pouch ileitis can occur above ileal pouches, usually causing visible ulceration that may be confused with Crohn's disease. 10
• Collagenous pouchitis is a rare form of pouch dysfunction that can affect the ileum above the pouch. 10

Reactive and Idiopathic Causes

• Reactive inflammation contributes approximately 15% of ileocecal inflammation cases. 3
• Idiopathic terminal ileitis (IDTI) is a diagnosis of exclusion with a reported prevalence between 0.5-7%, with 0-50% of patients potentially progressing to Crohn's disease. 12
• Acute nonspecific ileitis accounts for 41.2% of acute terminal ileitis cases in children. 8
• Most benign ileocecal ulcers of unknown origin are small in size (<1.0 cm) and represent 45% of cases. 11

Neoplastic Causes

• Neoplasms should be considered in patients with long-standing Crohn's ileitis who experience recrudescence of symptoms. 2
• Graft-versus-host disease is a potential etiology in transplant patients. 3

Emerging Causes

• Multisystem inflammatory syndrome in children (MIS-C) has emerged as one of the top three causes of acute terminal ileitis after the COVID-19 pandemic. 8
• The incidence of acute terminal ileitis has increased faster after the COVID-19 pandemic. 8

Key Diagnostic Pitfalls

• Superimposed infections with C. difficile or CMV on inflammatory bowel disease can complicate the clinical picture. 1
• Once therapy is started for inflammatory bowel disease, inflammation often appears segmental with relative rectal sparing, making initial colonoscopy findings critical. 1
• Ulcers at anastomotic sites may represent ischemic changes rather than active inflammatory changes and do not necessarily require treatment. 13
• Alcohol use in the week before colonoscopy shows significant association with ileitis in ulcerative colitis patients. 7