Crohn’s disease – Signs, Diagnosis, Treatment, Mnemonic

Crohn’s disease:

Crohn’s disease, also known as Crohn syndrome and regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea (which may be bloody if inflammation is at its worst), vomiting (can be continuous), or weight loss, but may also cause complications outside the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn’s disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals. This results in a chronic inflammatory disorder, in which the body’s immune system attacks the gastrointestinal tract possibly directed at microbial antigens. Crohn’s disease has wrongly been described as an autoimmune disease in the past; recent investigators have described it as an immune deficiency state.

Causes:

Crohn’s disease seems to be caused by a combination of environmental factors and genetic predisposition. Crohn’s is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn’s (approximately 1:200). The genetic data, and direct assessment of patient immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn’s is caused when the adaptive immune system tries to compensate for a deficient innate immune system.




This video tutorial on Crohn’s disease has been provided by: You and IBD

Signs and Symptoms:

Gastrointestinal:

Many people with Crohn’s disease have symptoms for years prior to the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the ‘patchy’ nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn’s disease experience chronic recurring periods of flare-ups and remission.
Abdominal pain may be the initial symptom of Crohn’s disease. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. The nature of the diarrhea in Crohn’s disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate.Visible bleeding in the feces is less common in Crohn’s disease than in ulcerative colitis, but may be seen in the setting of Crohn’s colitis. Bloody bowel movements are typically intermittent, and may be bright or dark red in color. In the setting of severe Crohn’s colitis, bleeding may be copious. Flatulence and bloating may also add to the intestinal discomfort.
Symptoms caused by intestinal stenosis are also common in Crohn’s disease. Abdominal pain is often most severe in areas of the bowel with stenoses. In the setting of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel obstruction. Although the association is greater in the context of ulcerative colitis, Crohn’s disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.
Perianal discomfort may also be prominent in Crohn’s disease. Itchiness or pain around the anus may be suggestive of inflammation, fistulization or abscess around the anal area or anal fissure. Perianal skin tags are also common in Crohn’s disease. Fecal incontinence may accompany perianal Crohn’s disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by non-healing sores (aphthous ulcers). Rarely, the esophagus, and stomach may be involved in Crohn’s disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.

Systemic:

Crohn’s disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohn’s disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohn’s disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohn’s disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn’s disease often feel better when they do not eat and might lose their appetite. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.

Extraintestinal:

In addition to systemic and gastrointestinal involvement, Crohn’s disease can affect many other organ systems. Inflammation of the interior portion of the eye, known as uveitis, can cause eye pain, especially when exposed to light (photophobia). Inflammation may also involve the white part of the eye (sclera), a condition called episcleritis. Both episcleritis and uveitis can lead to loss of vision if untreated.
Crohn’s disease that affects the ileum may result in an increased risk for gallstones. This is due to a decrease in bile acid resorption in the ileum and the bile gets excreted in the stool. As a result, the cholesterol/bile ratio increases in the gallbladder, resulting in an increased risk for gallstones.
Crohn’s disease is associated with a type of rheumatologic disease known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (arthritis) or muscle insertions (enthesitis). The arthritis can affect larger joints, such as the knee or shoulder, or may exclusively involve the small joints of the hands and feet. The arthritis may also involve the spine, leading to ankylosing spondylitis if the entire spine is involved or simply sacroiliitis if only the lower spine is involved. The symptoms of arthritis include painful, warm, swollen, stiff joints and loss of joint mobility or function.

Erythema nodosum on the back of a person with Crohn's disease.

© Crohnie – Own work Erythema nodosum – lesions that occur in some patients suffering from inflammatory bowel syndrome.

Crohn’s disease may also involve the skin, blood, and endocrine system. One type of skin manifestation, erythema nodosum, presents as red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal panniculitis. Another skin lesion, pyoderma gangrenosum, is typically a painful ulcerating nodule. Crohn’s disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism. Autoimmune hemolytic anemia, a condition in which the immune system attacks the red blood cells, is also more common in Crohn’s disease and may cause fatigue, pallor, and other symptoms common in anemia. Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn’s disease. Finally, Crohn’s disease may cause osteoporosis, or thinning of the bones. Individuals with osteoporosis are at increased risk of bone fractures.
Crohn’s disease can also cause neurological complications (reportedly in up to 15% of patients). The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache and depression.
Crohn’s patients often also have issues with small bowel bacterial overgrowth syndrome, which has similar symptoms.
In the oral cavity crohn’s patients may suffer from cheilitis granulomatosa and other forms of orofacial granulomatosis, pyostomatitis vegetans, recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population.

Pathophysiology:

During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. Certain characteristic features of the pathology seen point toward Crohn’s disease; it shows a transmural pattern of inflammation, meaning the inflammation may span the entire depth of the intestinal wall. Ulceration is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer – a characteristic sign known as skip lesions. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the epithelium. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with mononuclear cells, may infiltrate the crypts, leading to inflammation (crypititis) or abscess (crypt abscess). Granulomas, aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn’s disease. The granulomas of Crohn’s disease do not show “caseation”, a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as tuberculosis. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (metaplasia). One example of such metaplasia, Paneth cell metaplasia, involves development of Paneth cells (typically found in the small intestine and a key regulator of intestinal microbiota) in other parts of the gastrointestinal system.

Mnemonic:

Crohn's disease Mnemonic - Best Medical Mnemonics - Medical Institution Mnemonics

Crohn’s Disease Mnemonic

Diagnosis:

DIAGNOSIS — The diagnosis of Crohn disease is usually established with endoscopic findings or imaging studies in a patient with a compatible clinical history. Physical examination may be normal or show nonspecific signs (pallor, weight loss) suggestive of Crohn’s disease. More specific findings include perianal skin tags, sinus tracts, and abdominal tenderness.

Presenting symptoms frequently determine the order of subsequent testing. Colonoscopy is the most appropriate initial test for patients presenting with predominant diarrhea, while imaging studies may be more appropriate for those presenting with abdominal pain.

Laboratory studies — Initial blood studies for patients presenting with history and examination suggesting Crohn’s disease should include:

– Complete blood count (CBC)
– Blood chemistry including electrolytes, renal function tests, liver enzymes , and blood glucose
– Erythrocyte sedimentation rate (ESR)
– C-reactive protein (CRP)
– Serum iron and vitamin B12 levels

Of note, since vitamin B12 deficiency is a common manifestation in patients with Crohn’s disease with terminal ileum involvement, Schilling test (video) was used to determine if an individual with vitamin B12 deficiency was able to absorb vitamin B12 via the oral route. The test involved an oral dose of radiolabeled vitamin B12, with or without another substance to promote absorption, such as intrinsic factor, and a large parenteral dose of unlabeled vitamin B12 to saturate the vitamin B12 binding proteins and lead to massive excretion of the excess vitamin B12. If radiolabeled vitamin B12 was absorbed, it would be excreted in urine. Lack of access to the radiolabeled vitamin B12 used in the test, declining expertise, and increased availability of other testing with equal or better accuracy has made the Schilling test (video) obsolete in many institutions. Alternative tests for vitamin B12 absorption are under investigation.

Routine laboratory tests may be normal or they may reveal anemia, iron deficiency, elevated white blood cell count, B12 deficiency, and/or elevated erythrocyte sedimentation rate or CRP.

If diarrhea is present, a stool specimen should be sent for culture and examination for ova and parasites, as well as C. difficile toxin in appropriate clinical settings.

Endoscopy:

– Colonoscopy — Colonoscopy with intubation of the terminal ileum is used to establish the diagnosis of ileocolonic Crohn’s Disease. Endoscopic features include focal ulcerations adjacent to areas of normal appearing mucosa along with polypoid mucosal changes that give a cobblestone appearance. Areas of involvement are typical with segments of normal appearing bowel interrupted by large areas of disease. This pattern is different from the continuous involvement in ulcerative colitis. Pseudopolyps (hypertrophied masses of mucous membrane resembling polyps), as seen in ulcerative colitis, are also often present. Rectal sparing is common in Crohn’s disease as well.


Colonoscopy Findings:

Signs Crohn’s disease Ulcerative colitis
Terminal ileum involvement Commonly Seldom
Colon involvement Usually Always
Rectum involvement Seldom Usually
Involvement around
the anus
Common Seldom
Bile duct involvement No increase in rate of primary sclerosing cholangitis Higher rate of primary sclerosing cholangitis
Distribution of Disease Patchy areas of inflammation (Skip lesions) Continuous area of inflammation
Endoscopy Deep geographic and serpiginous (snake-like) ulcers Continuous ulcer
Depth of inflammation May be transmural, deep into tissues Shallow, mucosal
Stenosis Common Seldom
Granulomas on biopsy May have non-necrotizing non-peri-intestinal crypt granulomas Non-peri-intestinal crypt granulomas not seen

 

– Wireless capsule endoscopy — It has the advantage of providing visualization of the small bowel without exposing the patient to ionizing radiation.

 

Imaging studies — Imaging studies are most useful to evaluate the upper gastrointestinal tract and allow documentation of the length and location of strictures in areas not accessible by colonoscopy. Imaging has traditionally involved barium studies, such as barium enema or upper gastrointestinal series with small bowel follow-through (SBFT), though the use of CT and magnetic resonance enterography (MRE) is becoming more standard of care in imaging in patients with Crohn’s Disease.

– Colonic disease — Colonoscopy is the preferred study for evaluation of the lower bowel. Barium enema is a less desirable alternative, but may be indicated when a complete colonoscopy cannot be performed for technical reasons.

– Small bowel disease — Radiologic imaging is generally needed to evaluate patients with probable small bowel disease. Several imaging modalities are available, including conventional upper gastrointestinal series with SBFT, CT and CTE, enteroclysis, and MRI and MRE. We perform an MRE as it has the advantage of avoiding radiation.

 

Serologic markers — Disease markers to aid in the diagnosis of Crohn’s disease or indicate its severity have been described; however, their accuracy and predictive value remain to be determined.

– Antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA)

C-reactive protein — Elevated levels of CRP have been observed in patients with IBD and are generally higher in Crohn’s disease than in ulcerative colitis. CRP determination may have a role in distinguishing between these diseases, as well as in differentiating patients with IBD from those with symptoms caused by other disorders. CRP monitoring under therapy is useful in patients in whom it is elevated at baseline. Normalization of CRP under therapy documents the efficacy of the anti-inflammatory therapy.

 

Treatment:

There are several types of drugs used to treat Crohn’s disease. The first step usually involves reducing inflammation. Many people are first treated with sulfasalazine (Azulfidine).
If a person does not respond to sulfasalazine, the doctor may prescribe other types of drugs that contain 5-ASA. These other products include:

  • olsalazine (Dipentum)
  • balsalazide (Colazide, Colazal)
  • mesalamine (Asacol, Lialda, Pentasa, and others)

Corticosteroids such as prednisone are another class of drugs that reduce inflammation. A doctor is likely to prescribe an initial large dose of prednisone when the disease is very active. The dose is then tapered off. A problem with corticosteroids is the large number of possible side effects — some of them serious — such as a higher susceptibility to infection and stomach ulcers.

Crohn’s disease may also be treated with drugs that stop the immune system from causing inflammation. Immunomodulators change the way the immune system behaves. Immunosuppressants decrease the activity of the immune system. Immunostimulators increase the activity. Immunosuppressants prescribed for Crohn’s disease include:

  • azathioprine (Imuran, Azasan)
  • 6-mercaptopurine (6MP, Purinethol)
  • tacrolimus (Prograf)
  • Methotrexate (MTX, Rheumatrex, Mexate)
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