Nonspecific Inflammatory Bowel Diseases - Crohn's disease, Ulcerative colitis

From WikiLectures

Crohn’s Disease

Crohn’s disease (colitis regionalis, ileitis terminalis) is a chronic inflammatory bowel disease. The inflammation can occur in any part of the digestive tract and has a segmental pattern—affected areas are separated by sections of healthy mucosa. The most affected region is the terminal ileum. The inflammation involves the entire thickness of the organ wall and is characterized by the presence of non-caseating epithelioid granulomas.

Epidemiology

Crohn’s disease occurs more often in younger people. The highest prevalence is in the 30–39 age group. About 10% of patients are diagnosed before the age of 17.

The average prevalence in adults is about 130 per 100,000, with an incidence of 5.6 per 100,000 inhabitants.

The incidence in children is increasing, reaching up to 9–10 per 100,000, especially in Northern Europe. The incidence in children in the Czech Republic is 6.2 per 100,000.

Risk Factors

First-degree relatives have a 10–35 times higher risk of developing the disease.

Genetic mutations.

High hygiene standards in childhood, smoking, early appendectomy, and nonsteroidal anti-inflammatory drugs (NSAIDs).


Etiopathogenesis

The cause of the disease is not yet known. It is likely a dysregulation of the immune response to common bacterial antigens. During this autoimmune reaction, transmural inflammation develops—meaning inflammation that affects the entire thickness of the intestinal wall and often extends to the mesentery. Epithelioid granulomas, ulcerations, and fissures form within the intestinal wall. Intramural and intraperitoneal abscesses or fistulas (especially in the anal region) are also commonly observed. Due to long-term inflammation, narrowing of the intestine may occur as a result of tissue scarring (fibrotic strictures).

A characteristic feature of Crohn’s disease is segmental involvement of the gastrointestinal tract—alternating inflamed and unaffected sections (“skip lesions”). Commonly affected areas include the terminal ileum and the ascending colon, but any part of the gastrointestinal tract can be involved.

Pathological Image

The entire intestinal wall is affected, and the inflammation is segmental or multisegmental. Typically, affected sections alternate with unaffected ones (in contrast to ulcerative colitis).

Macroscopical Image

Macroscopically, there is thickening of the intestinal wall and mesentery. Regional lymph nodes are often enlarged. The mucosa is hypertrophic and edematous. The appearance is often compared to cobblestones—elongated aphthous ulcers over lymphoid follicles surrounded by unaffected mucosa, raised openings of fistulas, and pseudopolyps. Involvement of the serosa leads to adhesions, within which fistulas may form. As the disease progresses, fibroproduction occurs, leading to the development of stenoses.

Microscopical Image

Under the microscope, mucosal edema with polymorphonuclear infiltration is observed, followed by fibroproduction with the formation of tuberculoid granulomas (composed of epithelioid cells and Langhans-type giant cells, which—unlike in tuberculosis—do not undergo caseation) in the submucosa, subserosa, and regional lymph nodes.

Clinical Image

Like all autoimmune diseases, Crohn’s disease manifests in multiple systems. The typical presentation is in the digestive tract, but the eyes, skin and mucous membranes, liver, pancreas, and kidneys can also be affected, and blood homeostasis is often impaired.

Intestinal Manifestation

Common symptoms include abdominal pain and chronic diarrhea (rarely with blood). Around the anus, fissures, perianal abscesses, fistulas, and skin tags (anal folds—skin outgrowths at the junction of the anal opening and the skin) may occur.

Extraintestinal manifestations

Extraintestinal symptoms occur in more than 40% of patients. They often precede intestinal symptoms by several years. These are mostly nonspecific symptoms such as recurrent fever, anorexia, weight loss, and delayed growth, especially in children. The main systems that may be affected include:

  • Skeletal system: growth impairment and osteoporosis (proinflammatory cytokines suppress growth, reduce IGF-1 production, and stimulate bone resorption; also influenced by insufficient energy intake, malabsorption, loss of proteins and trace elements in stool, and long-term corticosteroid therapy).
  • Skin and mucous membranes: aphthous stomatitis, gingivitis, cheilitis granulomatosis, erythema nodosum on the lower legs, and pyoderma gangrenosum.
  • Eyes: iritis, uveitis, episcleritis; rare in children; corticosteroid therapy may induce cataracts and glaucoma.
  • Liver and pancreas: primary sclerosing cholangitis, gallstones; pancreatitis following treatment with azathioprine or mesalazine.
  • Vascular system: hypercoagulable state (thrombocytosis, increased levels of fibrin, factors V and VII, decreased antithrombin), which may lead to deep vein thrombosis, pulmonary embolism, or stroke.
  • Kidneys and urinary tract: fistulas and urinary stones.

Complications

The inflammation often spreads to surrounding tissues and forms fistulas (i.e., channels connecting the inflamed area with another site). Fistulas may be:

  • Internal: enteroenteric, enterocolic, enterovesical, rectovaginal
  • External: involving the abdominal wall or perineum

Other complications include:

  • Formation of abscesses, which may be interloop, pelvic, retroperitoneal, or hepatic
  • Intestinal stenosis, which is dangerous due to the risk of ileus
  • Perianal fissures
  • Intestinal perforation and its complications, such as peritonitis
  • Massive bleeding
  • Toxic megacolon
  • Malignant transformation (development of carcinoma)

Diagnosis

The diagnosis of the disease is classically based on medical history, physical examination, and laboratory and imaging methods. Patients often report abdominal pain, chronic diarrhea, growth delay (which may precede gastrointestinal symptoms), and recurrent fevers. During physical examination, typical changes of the skin and mucous membranes, as well as the anal and genital regions (fistulas, skin tags), may be found, and an abdominal mass may be palpable.

Laboratory diagnostics

  • Markers of acute and chronic inflammation: CRP, ESR, albumin levels, complete blood count – anemia, leukocytosis, thrombocytosis
  • Antibodies against Saccharomyces cerevisiae (ASCA), positive in more than 50% of patients
  • Parameters of liver, kidney, and pancreatic function – due to the risk of involvement of these organs
  • Fecal calprotectin – an indicator of mucosal inflammation (a leukocyte cytosolic protein released after activation or lysis of leukocytes)
  • Occult blood in stool

Imaging methods

  • Ultrasound: thickening of the intestinal wall and detection of abdominal abscesses
  • MR enterography, MRI of the pelvic floor
  • Previously used enterography (enteroclysis): contrast (barium suspension) administered into the duodenum under X-ray control, followed by methylcellulose solution
  • Irrigography: X-ray examination of the colon after rectal administration of contrast (used when endoscopy is not possible)
  • Fistulography: contrast injection into a fistula under X-ray control
  • CT scan: diagnosis of abdominal abscesses

Endoscopic examination

  • Colonoscopy: allows both macroscopic and microscopic examination of the mucosa (aphthous lesions, ulcerations, cobblestone appearance, strictures); in children, performed under general anesthesia
  • Gastroscopy
  • Capsule endoscopy: a miniature digital camera in a plastic capsule (11 × 26 mm) that enables examination of the small intestine (the segment between gastroscopy and colonoscopy); can be used from about 6 years of age, and in small children it may be inserted into the duodenum via gastroscopy.

Therapy

Pharmacological therapy

  • Corticosteroids – used to induce remission during acute inflammation; remission is achieved in about 85% of patients
    • Systemic: Prednisone 1–2 mg/kg/day (maximum 60 mg/day) for 2–4 weeks, followed by gradual tapering
    • Alternatively, locally acting Budesonide – less effective but with fewer side effects
  • Immunomodulatory drugs – used to maintain remission without corticosteroids
    • Thiopurines – require monitoring of blood count, liver function tests, and amylase; risk of allergic reactions
    • Methotrexate
  • Antibiotics – Ciprofloxacin, Metronidazole
  • 5-aminosalicylates – Sulfasalazine, Mesalazine (more effective in ulcerative colitis) [5]

Targeted therapy (biological agents)

  • Infliximab (Remicade) – chimeric monoclonal antibody (human + mouse) against TNF-α; used in patients resistant to conventional therapy
  • Adalimumab (Humira) – fully human monoclonal antibody [5]

Nutritional therapy

  • Remission can be induced by exclusive enteral nutrition – a complete elemental diet based on amino acids for 4–6 weeks reduces inflammation (especially in children), but relapse after discontinuation is common [5]

Surgical therapy

  • There is a risk of recurrence even after successful surgery
  • Indicated in complications (perforation, bleeding, fistulas, abscesses, strictures, significant growth retardation, tumors) [5]

Procedures include:

  • Resection with anastomoses or stomas
  • Strictureplasty and balloon dilation of stenoses
  • Abscess drainage
  • Fistulotomy

Principles:

  • Resections should be as limited as possible (due to the likelihood of repeated surgeries; at least 60 cm of small intestine should be preserved)
  • Strictureplasty is preferred over resection when feasible
  • End-to-end anastomoses
  • Stoma formation in acute conditions or when rectal reconstruction is not possible
  • Avoid creating a pouch in rectal reconstruction

Types of operations:

  • Segmental resection of the small and large intestine
  • Ileocecal resection with ileo-ascending anastomosis
  • Right hemicolectomy with ileo-transverse anastomosis
  • Subtotal colectomy with ileorectal anastomosis
  • Proctocolectomy with ileostomy
  • Abdominoperineal resection with colostomy

If the rectum is not affected, it is preferable to preserve it even with a permanent ileostomy (to protect pelvic nerve plexuses and maintain sexual function), although this requires regular monitoring for inflammatory lesions.

Appendectomy carries a risk of fistula formation, but it is often performed so that appendicitis can be excluded as a cause of symptoms in case of recurrence.

Prevention

There is no known prevention, as the cause of the autoimmune dysregulation is not yet fully understood.


ULCERATIVE COLITIS

Ulcerative colitis (idiopathic proctocolitis, proctocolitis idiopathica, ICD-10: K51) is a rare autoimmune type of inflammation of the digestive tract. It is a hemorrhagic–purulent to ulcerative inflammation affecting the mucosa and submucosa of the rectum and the adjacent part of the colon (proctocolitis), or sometimes the entire colon (pancolitis); the small intestine is never involved. About 20% of patients are diagnosed before the age of 20.

Epidemiology

  • Prevalence: 150 per 100,000 inhabitants
  • 19% of patients are children under 18 years of age – pediatric prevalence: 29 per 100,000; pediatric incidence: 1–3 per 100,000
  • The incidence has not been increasing in recent years (unlike Crohn’s disease)
  • The average age of patients is 11 years

Etiopathogenesis

The cause is unknown. One of the most likely theories is a dysregulation of the immune response to common bacterial antigens. The inflammation affects only the rectum and colon, to varying extents. In children, pancolitis is common. The inflammation is continuous, and the distal parts of the colon are usually more severely affected.

Pathological findings

Only the mucosa and submucosa are affected. Unlike Crohn's disease, the involvement is continuous. Macroscopically, there is contraction of the affected segment; the mucosa is hypertrophic and edematous with numerous ulcers with raised margins, the serosa is shiny, and the mesocolon is not thickened. Microscopically, crypt abscesses are present (dilated crypts filled with polymorphonuclear cells; their breakdown leads to detachment of the mucosa and ulceration).

Clinical presentation

Gastrointestinal symptoms

  • Bloody diarrhea
  • Lower abdominal pain associated with defecation
  • Tenesmus (painful urge to defecate with a persistent feeling of incomplete evacuation)

Based on localization, two main syndromes are distinguished:

  • Rectal syndrome: tenesmus with passage of small amounts of stool or mucus with blood
  • Colitic syndrome: crampy abdominal pain with watery diarrhea containing blood and mucus, and albumin loss

Extraintestinal manifestations

These are significantly less frequent than in Crohn's disease. They include:

  • Arthralgia
  • Erythema nodosum
  • Pyoderma gangrenosum

Complications

  • Iridocyclitis (affects about 1% of patients)
  • Glaucoma and cataracts due to corticosteroid therapy
  • Primary sclerosing cholangitis – may precede manifestations of ulcerative colitis
  • “Overlap syndrome” with autoimmune hepatitis, primary sclerosing cholangitis, and ulcerative colitis
  • Thromboembolic complications
  • Toxic megacolon (risk factors: anticholinergics, opioids, irrigography, colonoscopy)
  • Colorectal carcinoma (after 10 years in 2% of patients, after 50 years in 40%) – prevention with 5-ASA and folic acid

Diagnosis

  • Medical history: chronic diarrhea, rectal bleeding, localized abdominal pain, fatigue, weight loss
  • Physical examination: pallor, tender resistance in the left lower abdomen
  • Laboratory findings: mildly to moderately elevated inflammatory markers, anemia
  • pANCA antibodies: positive in about 70%
  • Other parameters similar to those in Crohn's disease

Endoscopy

  • Method of choice; both upper and lower endoscopy are performed (to differentiate from Crohn's disease)

Imaging

  • Ultrasound: thickened intestinal wall
  • Irrigography: used only when strictures cannot be passed endoscopically; shows loss of colonic haustration, pseudopolyps, strictures
  • Leukocyte scintigraphy: not routinely used (only nonspecific detection of inflammation)

Therapy

Main goals: induction and maintenance of remission, prevention of complications

Pharmacological therapy

  • 5-aminosalicylates: Sulfasalazine, Mesalazine – inhibit arachidonic acid metabolism and have mild anti-inflammatory effects
  • Corticosteroids: locally acting Budesonide or systemic Prednisone
  • Immunomodulators: Azathioprine, 6-mercaptopurine
  • Cyclosporine A: used in corticosteroid-resistant cases
  • Tacrolimus: an immunosuppressant from the macrolide group

Targeted (biological) therapy

  • Infliximab (Remicade) – chimeric monoclonal antibody against TNF-α

Probiotics

  • E. coli Nissle – in adults with mild disease, has an effect comparable to mesalazine

Nutritional therapy

  • Enteral nutrition is less effective than in Crohn's disease

Surgical therapy

Urgent indications: perforation, bleeding, endotoxemic shock, toxic megacolon

  • Subtotal colectomy with ileostomy and closure of the rectal stump (Hartmann procedure) or exteriorization as a mucous fistula (Mikulicz procedure)

Elective surgery: indicated in failure of conservative treatment, mucosal dysplasia or carcinoma, strictures, or extraintestinal manifestations

  • Total proctocolectomy with ileostomy or ileoanal anastomosis with a pouch (J, S, or W pouch)
  • The pouch serves as a stool reservoir, eliminating the need for a permanent ileostomy

Supportive therapy

  • Psychological care



Top of Form


Bottom of Form

Retrieved from "https://www.wikilectures.eu/index.php?title=Nonspecific_Inflammatory_Bowel_Diseases_-_Crohn%27s_disease,_Ulcerative_colitis&oldid=98608"