CROHN DISEASE

pediagenosis    February 19, 2026    Digestive , Organ , science    Comment   

CROHN DISEASE

IMAGING AND REGIONAL VARIATIONS

In the United States, approximately 1.5 million individuals have Crohn disease. Crohn disease is one disease in a larger group of inflammatory bowel disorders, which includes ulcerative colitis, indeterminate colitis, and microscopic colitis. Crohn disease is a progressive illness characterized by transmural inflammation within the digestive tract that may occur anywhere from mouth to anus. Skip lesions of normal and inflamed, “cobblestoned” mucosa describe its classic luminal appearance. The phenotype is characterized by the disease’s severity, site, and type of manifestation, whether inflammatory, fibrostenotic, or fistulizing.

Historically, a bimodal peak in age of onset between 15 and 40 years and 50 and 80 years has been observed. Individuals of Jewish descent have a higher incidence of inflammatory bowel disorder compared with the non-Jewish population. The incidence is lower in African Americans and Latin American populations compared with white populations. There is a slight female pre-dominance in patients who are diagnosed at an early age. This may be due to gender-specific hormonal changes, though this is not completely understood.

Individuals with a first-degree relative with Crohn disease have a risk up to 20 times greater of developing an inflammatory bowel disorder phenotype. Monozygotic twin studies indicate that genetics may contribute more to Crohn disease than to ulcerative colitis, with concordance rates of 50% versus 19%, respectively. Indeed, genome-wide association studies have been critical in identifying more than 160 susceptibility loci for inflammatory bowel disorders. Many signaling pathway defects in the innate immune system, autophagy pathway, and major histocompatibility complex have been identified as contributing to the pathogenesis. For instance, patients with Crohn disease who have a NOD2 (CARD 15) gene mutation exhibit a risk of ileal disease that is higher than those who lack the mutation. Up to 20% of the general population carry this mutation and do not have underlying Crohn disease, however.

Indeed, there is considerable genetic variability between and within different Crohn disease phenotypes. Hence, because twin studies have not demonstrated a 100% concordance, there has been increasing inquiry into the contribution of diet and the environment to disease pathogenesis. Several studies demonstrate that Western diets high in processed foods, refined sugars, and fried foods and low in sources of vegetables and fruits are associated with an increased risk for inflammatory bowel disorders. Whereas inflam-matory bowel disorders in developing nations were rare in the past, major cities in such nations now demonstrate an increased or equal incidence of the disorders, possibly owing to expansion of Western diets into these regions. Recently, consuming a pescovegetarian diet has been associated with a decreased trend toward flares and may thus exhibit antiinflammatory value.

Many of the aberrant signaling pathways elucidated through genome-wide association studies also demonstrate improper innate immune system interpretation of bacterial antigens within the intestinal lumen. Taken together, these studies suggest that genetically predisposed individuals may improperly interpret normal intestinal luminal antigens, made up of bacteria and/or dietary components, and instead immunologically react by increasing inflammatory cell activity within the intestine, leading to inflammatory bowel disorders.

Symptoms of Crohn disease are inherently variable, depending on the severity, location, and complications of the disease. Abdominal pain, diarrhea, lethargy, malaise, fatigue, and unintentional weight loss are common. The diarrhea is generally nonbloody, in contrast to the overtly bloody diarrhea of ulcerative colitis.

In children, malabsorption from Crohn disease presents with growth failure, weight loss, or micronutrient deficiencies (vitamins A, B12, D, and E, and zinc).

Plate 2-35
FISTULIZING (PENETRATING) CROHN DISEASE

At initial diagnosis, most Crohn disease patients will exhibit mucosal inflammatory disease. Approximately one third of patients have focal ileal inflammation, up to 20% have colitis alone, and at least half have ileocolonic involvement. Nearly 75% to 80% of patients will, at some point, have small bowel involvement. Oral and gastroduodenal lesions are most of the rare upper intestinal Crohn disease manifestations (5%). One third of patients exhibit perianal disease. Fistulas may also occur elsewhere, as detailed below.

Over time, uncontrolled transmural inflammation will result in fibrosis, leading to fibrostenotic stricture or fistulous disease. Natural history studies demonstrate that 20 years after the diagnosis of Crohn disease, more than 50% of patients develop a stricture of 25% in the small bowel and of 10% in the colon. Obstructive symptoms may ensue, or sometimes, the back pressure from stenosis may prompt the development of a secondary fistula proximal to the obstruction. Stenotic lesions may be fibrotic or inflammatory. The former may require serial endoscopic balloon dilatation, whereas the latter may respond to antiinflammatory medication. Failure to respond and/or clinical signs and symptoms of obstruction may warrant segmental bowel resection.

Approximately 20% to 50% of patients will develop predominant fistulizing (penetrating) disease. Over half of these will be perianal in location, with one quarter characterized as enteroenteric and around 10% as rectovaginal. Notably, fistulas can extend from any loop of bowel to any other visceral, peritoneal, or cutaneous surface. This may result in simple or complex abscesses necessitating seton placement, surgery, or radiologically guided drainage. Regardless, the symptoms can be devastating and challenging to treat.

Importantly, extraintestinal manifestations of inflammatory bowel disorders provide important insights, because they may precede the symptoms of a flare or herald uncontrolled disease activity.

Extraintestinal manifestations that may correlate with disease activity include uveitis, oral aphthous ulcerations, erythema nodosum, and an asymmetric peripheral arthropathy affecting the large joints of the periphery. Multiple organ systems can be associated with inflammatory bowel disorders independent of colitis activity.

Ophthalmic disease additionally involves episcleritis, keratopathy, and corneal ulcers that may require topical corticosteroids. Half of patients will have asymptomatic but aberrant pulmonary function tests. However, interstitial lung disease, pulmonary fibrosis, and vasculitis can occur. Ileal disease promotes fat malabsorption, resulting in excess intestinal calcium reabsorption that ultimately precipitates with oxalate in the kidney, causing nephrolithiasis and pyelonephritis. Additional cutaneous lesions include pyoderma gangrenosum, Sweet syndrome, and rare primary cutaneous Crohn disease without intestinal involvement. Nutrient malabsorption results in secondary cutaneous lesions, such as glossitis (with B complex deficiency) or acro-dermatitis enteropathica (with zinc deficiency). Auto-immune (vitiligo) or atopic (psoriasis) lesions may be associated, too. Other musculoskeletal manifestations include hypertrophic osteoarthritis with clubbing, sacroiliitis, or spondyloarthropathies. Elevated liver enzymes may herald primary sclerosing cholangitis, although it is more commonly observed in ulcerative colitis than Crohn disease.

Laboratory studies may demonstrate iron deficiency anemia from chronic intestinal losses or megaloblastic anemia from vitamin B12 malabsorption due to ileitis. Serologic inflammatory markers such as the sedimentation rate and C-reactive protein levels are nonspecific but may be elevated. Elevated fecal calprotectin is

consistent with inflammation specific to the intestine, although bacterial infections and use of proton pump inhibitors or nonsteroidal antiinflammatory drugs may falsely elevate this value. Notably, low vitamin D levels have been associated with severity of disease and may have an immunologic role in disease pathogenesis.

Upper or lower gastrointestinal tract x-rays with contrast are employed for macroscopic assessment for intestinal stricture or rectovaginal fistula. Cross-sectional imaging is initially preferred, however. CT scans afford excellent imaging but result in unacceptable cumulative radiation exposure, increasing the risk of secondary malignant disease. For this reason, MRI is preferred. Magnetic resonance enterography is a highly sensitive assay for the assessment of small bowel inflammation, stricture, and fistulous disease.

Colonoscopic investigation aids ileal surveillance and may demonstrate deep, cratered ulcers consistent with Crohn disease. Pseudopolyps are not adenomatous but signify prior inflammation as the natural disease activity waxes and wanes throughout life. Wireless video capsule endoscopy affords valuable small bowel surveillance for Crohn disease sequelae. Notably, individuals with known stenosis are not appropriate candidates for capsule endoscopy. Histologic studies demonstrate crypt abscesses and cryptitis with a focal, transmural inflammatory infiltrate of neutrophils, plasma cells, and lymphocytes within the mucosa and submucosa. Granulomas are neither necessary for nor pathognomonic for diagnosis. Tuberculosis should be excluded, especially in those with ileal disease.

Because unchecked colitis increases the risk of surgery, malignant disease, and worsened morbidity, luminally active Crohn disease warrants immunosup-pression. Systemic corticosteroids have been employed in inducing mucosal remission. The resulting steroid dependency also causes untold suffering via the consequences of chronic steroid use (e.g., infection, avascular necrosis, hirsutism, acne, adrenal insufficiency). Therefore, noncorticosteroid regimens were developed. Although they were initially employed in Crohn disease, oral and rectal mesalamine therapies are ineffective at inducing remission; they do have efficacy in ulcerative colitis. Immunomodulators such as methotrexate, azathioprine, and 6-mercaptopurine are used to maintain remission once it is achieved. Several biologic antibodies have been developed to quench key signaling factors in the inflammatory pathway. Among these are anti–tumor necrosis factors, anti–alpha-4/beta-7 integrins (vedoluzimab), and anti–interleukin-12 or 23 agents. Numerous other agents are in development, including novel oral agents. Biologic agents alone or in combination with immunomodulators have demonstrated efficacy in inducing remission and promoting fistula closure in biologically naïve patients. Quinolone and metronidazole antibiotics are used in the setting of perianal fistulizing disease but are not intended for indefinite therapy.

Recalcitrant disease often responds to diversion, resulting in mucosal healing. Surgical resection of diseased segments of intestine may improve the quality of life drastically but typically suggest the need for future surgical interventions due to recurrent disease. Hence, early biologic immunosuppression is recommended to prevent insidious inflammation and consequences of recurrent disease in the form of stricture and/or fistula in the future. Tobacco use is discouraged because it increases Crohn disease flares, prevents wound healing, and can help promote the development of stricture.

Plate 2-36
EXTRAINTESTINAL MANIFESTATIONS IN CROHN DISEASE

Numerous quality measures have been established as goals in inflammatory bowel disorders. These include annual tuberculosis assessment, hepatitis B screening prior to anti–tumor necrosis factor induction, initiation of corticosteroid-sparing agents, prophylactic immunization (pneumococcal/influenza), bone density assessment and supplementation, vitamin D supplementation, tobacco cessation education, venous thromboembolism prophylaxis, and ruling out of Clostridium difficile infection during flares. Interdisciplinary coordination between adult and pediatric transitional providers, surgeons, social workers, dieticians, ostomy nurses, and psychiatrists optimizes the overall quality of care.