Penyakit Crohn

01Pathophysiology

Crohn's disease is a chronic inflammatory condition that can involve any segment of the gastrointestinal tract from the mouth to the anus, though it most commonly affects the terminal ileum and proximal colon. The hallmark is transmural inflammation, meaning the inflammatory process extends through the full thickness of the bowel wall, from mucosa to serosa. This is the single most important pathologic distinction from ulcerative colitis, which only involves the mucosa and submucosa.
The underlying mechanism involves a dysregulated immune response. In genetically predisposed individuals (particularly those carrying NOD2/CARD15 mutations), the innate immune system fails to properly handle commensal gut bacteria. This leads to an exaggerated Th1 and Th17 cell-mediated immune response, with overproduction of pro-inflammatory cytokines, most notably tumor necrosis factor-alpha (TNF-alpha), interleukin-12, and interleukin-23. The sustained inflammation drives tissue damage, fibrosis, and the formation of granulomas.
Because the inflammation is transmural, it directly explains the pattern of complications. Full-thickness damage allows the formation of fistulas (abnormal tracts connecting the bowel to other organs, skin, or adjacent bowel loops), abscesses (from walled-off perforation), and strictures (from chronic fibrosis and scarring that narrows the intestinal lumen). The "creeping fat," a classic gross pathology finding, refers to mesenteric adipose tissue wrapping around the inflamed bowel surface and is considered pathognomonic at surgery or autopsy.
The skip lesion pattern, where segments of diseased bowel are separated by stretches of normal-appearing mucosa, is explained by the patchy nature of the immune activation. This is in contrast to the continuous, proximal-to-distal spread seen in ulcerative colitis.
Malabsorption develops because of inflammation in the terminal ileum, which is the primary absorption site for bile salts and vitamin B12. Loss of bile salt reabsorption leads to fat malabsorption, steatorrhea, and deficiency of fat-soluble vitamins (A, D, E, K). Vitamin B12 deficiency can produce a megaloblastic anemia. The chronic systemic inflammation combined with poor nutrient absorption accounts for the weight loss, growth retardation in children, and fatigue that dominate the clinical picture.

02Classification and Clinical Manifestation

The Montreal Classification is the standard framework for categorizing Crohn's disease based on age at diagnosis, location, and behavior.

Montreal Classification:

Intestinal Manifestations:

Extraintestinal Manifestations:

03Diagnostic Workup

The diagnostic approach begins with clinical suspicion based on the characteristic triad of chronic diarrhea, abdominal pain, and weight loss in a young patient. The best initial step in the workup is to obtain inflammatory markers (CRP, ESR) and fecal calprotectin. Fecal calprotectin is particularly useful in the outpatient setting because it reliably distinguishes organic inflammatory disease from irritable bowel syndrome, sparing many patients from unnecessary colonoscopy.
Once inflammatory bowel disease is suspected, the gold standard and most accurate test is colonoscopy with terminal ileum intubation and multiple biopsies. The endoscopist should obtain biopsies from both affected and apparently normal segments to demonstrate the skip pattern. The presence of non-caseating granulomas on histology is highly suggestive of Crohn's, though granulomas are found in only about 30% of mucosal biopsies.
Cross-sectional imaging, particularly CT enterography or MR enterography, is used to evaluate the small bowel beyond the reach of the colonoscope and to identify complications such as strictures, fistulas, and intra-abdominal abscesses. MR enterography is preferred in younger patients and for perianal disease assessment because it avoids ionizing radiation.
Serologic markers (ASCA positive / p-ANCA negative) can support the diagnosis in cases of indeterminate colitis, where histologic features overlap between Crohn's and ulcerative colitis. However, serology alone is never sufficient to make or exclude the diagnosis.
Before finalizing a diagnosis of Crohn's, always ensure that infectious etiologies have been excluded. Stool cultures and C. difficile testing are mandatory, as infectious colitis can perfectly mimic an IBD flare.

04Management and Treatment

Acute Management:
The first decision point in an active flare is severity assessment. For mild disease limited to the ileocecal region, budesonide is preferred over systemic corticosteroids because it has topical activity with high first-pass hepatic metabolism, minimizing systemic side effects. Budesonide 9 mg daily is given for 8 weeks, then tapered by 3 mg every 2-4 weeks.
For moderate-to-severe disease, systemic corticosteroids (prednisone 40-60 mg/day) remain the first-line induction agent. However, steroids are strictly a bridge therapy. They must never be used for maintenance because long-term use leads to osteoporosis, adrenal suppression, glucose intolerance, and increased infection risk without preventing relapse. The exam frequently tests the principle that corticosteroids induce remission but do not maintain it.
Anti-TNF agents (infliximab, adalimumab) are increasingly used as first-line induction therapy in moderate-to-severe disease under a "top-down" strategy, especially in patients with high-risk features (young age, perianal disease, extensive disease, deep ulceration). The combination of an anti-TNF agent with a thiopurine (azathioprine) is more effective than either alone for both induction and maintenance, as demonstrated in the SONIC trial.
Maintenance Therapy:
Once remission is achieved, the goal is to maintain it with a steroid-sparing agent. The main options are thiopurines (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day), methotrexate (25 mg IM/SC weekly for induction, then 15 mg weekly for maintenance), or biologic agents. Before starting a thiopurine, TPMT (thiopurine methyltransferase) or NUDT15 enzyme activity must be checked to prevent life-threatening myelosuppression in patients with low or absent enzyme activity.
For patients who fail anti-TNF therapy, second-line biologics include vedolizumab (anti-integrin, gut-selective) and ustekinumab (anti-IL-12/23). These are tested as alternatives in the setting of anti-TNF failure or intolerance.
Surgical Management:
Surgery is not curative in Crohn's disease but is required for complications such as obstruction, perforation, abscess not amenable to percutaneous drainage, and medically refractory disease. The principle is to conserve as much bowel as possible to prevent short bowel syndrome. Strictureplasty is preferred over resection for short fibrotic strictures. Postoperative recurrence is common, with the neo-terminal ileum being the most frequent site. Mesalamine, thiopurines, or anti-TNF agents are used postoperatively to reduce recurrence, and colonoscopic surveillance is recommended within 6-12 months after surgery.
Contraindications and Cautions:
Methotrexate is absolutely contraindicated in pregnancy (teratogenic, Category X). Anti-TNF agents require screening for latent tuberculosis (PPD or interferon-gamma release assay) and hepatitis B before initiation, as reactivation of either can be fatal. Thiopurines carry an increased risk of lymphoma, particularly hepatosplenic T-cell lymphoma in young males receiving combination therapy with anti-TNF agents.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on Crohn's disease questions is by confusing it with ulcerative colitis. The vignette will often include a deliberate mix of features, and the discriminating detail comes down to a few findings: transmural vs. mucosal inflammation, skip lesions vs. continuous involvement, non-caseating granulomas, fistula or perianal disease, and small bowel involvement. If any of these appear, the answer is Crohn's regardless of what other features are present.
A second frequent trap involves the management of steroid use. A question may describe a patient who has been on prednisone for several months with good symptom control, then ask for the "next best step." Students who select "continue prednisone" will be wrong. The tested principle is that steroids are never appropriate for maintenance therapy, and the answer is always to transition to a steroid-sparing agent such as azathioprine or an anti-TNF biologic.
Another high-yield testing point is the young patient with right lower quadrant pain who undergoes surgery for presumed appendicitis, but the appendix is found to be normal and the terminal ileum is inflamed. This is the classic "surprise Crohn's" scenario, and the correct next step is biopsy of the terminal ileum, not appendectomy.
Students also frequently miss the association between ileal Crohn's disease and specific nutritional deficiencies. Terminal ileum disease causes B12 and bile salt malabsorption. Loss of bile salts leads to fat malabsorption, which increases free oxalate absorption in the colon, producing calcium oxalate kidney stones. Meanwhile, cholesterol gallstones form because bile salt depletion disrupts the cholesterol-bile salt-lecithin solubility ratio. A question presenting kidney stones or gallstones in a patient with chronic diarrhea is testing this pathway.
Finally, before starting any anti-TNF therapy, the vignette may test whether you screen for latent tuberculosis and hepatitis B. Failing to select this screening step before initiating infliximab or adalimumab is a commonly tested error. The core competency being assessed across all Crohn's questions is pattern recognition of transmural bowel inflammation, logical sequencing of diagnostic and therapeutic steps, and understanding the downstream consequences of ileal disease on distant organ systems.