Crohn Disease Clinical Presentation

Updated: Jan 06, 2017
  • Author: Leyla J Ghazi, MD; Chief Editor: Praveen K Roy, MD, AGAF  more...
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Presentation

History

Patients with suspected Crohn disease should be evaluated initially by their primary care team, and symptoms should be elicited in detail. Obtain a complete medical, surgical, social, and family history, and perform a detailed review of systems. Preliminary laboratory data (eg, inflammatory and anemia markers) may be helpful. If Crohn disease is suspected, the patient should be promptly referred to a gastroenterologist for consultation.

In children, document growth parameters; growth failure may precede gastrointestinal (GI) symptoms by years. The etiology of growth failure is multifactorial, with nutritional, hormonal, and disease-related factors all contributing. Any child or adolescent with persistent alterations in growth or delayed puberty should undergo appropriate diagnostic evaluation for Crohn disease.

General manifestations

Low-grade fever, prolonged diarrhea with abdominal pain, weight loss, and generalized fatigability are usually reported. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain precedes and may be partially relieved by defecation. Diarrhea is usually not grossly bloody and is often intermittent. If the colon is involved, patients may report diffuse abdominal pain accompanied by mucus, blood, and pus in the stool. [1, 2, 11, 42, 43]

It is important to note that colonic Crohn disease may be clinically indistinguishable from ulcerative colitis, with symptoms of bloody mucopurulent diarrhea, cramping abdominal pain, and urgency to defecate.

Crohn disease of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia. Initially, these symptoms may be quite subtle. Patients with gastroduodenal involvement more commonly have anorexia, nausea, and vomiting. [44] Those with perianal disease may have debilitating perirectal pain, malodorous discharge from the fistula, and disfiguring scars from active disease or previous surgery.

Patients may also present with complaints suggestive of intestinal obstruction. Initially, the obstruction is secondary to inflammatory edema and spasm of the bowel and manifests as postprandial bloating, cramping pains (lower right quadrant), and borborygmi. Once the bowel lumen becomes chronically narrowed from fibrosis, patients may complain of constipation and obstipation. These symptoms generally do not improve with anti-inflammatory agents. Complete obstruction may sometimes be caused by impaction of undigested foods.

Enterovesical fistulae may manifest as recurrent urinary tract infections and pneumaturia, enterovaginal fistulae as feculent vaginal discharge, and enterocutaneous fistulae as feculent soiling of the skin. Development of fistulae into the mesentery or luminal microperforation may result in intra-abdominal or retroperitoneal abscess formation.

Location and extent

The patient’s clinical presentation is primarily determined by the location and extent of the disease. Although any area of the GI system may be affected in patients with Crohn disease, the most common site of the chronic inflammatory process is the ileocecal region, followed by the colon (about 20%), the small intestine alone (about 30%), the stomach (rarely), and the mouth. [8] The esophagus is very rarely involved. [1]

The terminal ileum is involved in 50-70% of children. More than half of these patients also have inflammation in various segments of the colon, usually the ascending colon. Gastric inflammation, duodenal inflammation, or both may be observed in as many as 30-40% of children with Crohn disease. The primary pancreatic manifestation is pancreatitis.

About 45% of cases of Crohn disease occur in the ileum and colon, 20% solely in the colon, 33% in the small bowel, and 5% in the gastroduodenal region and perianal region alone (fistula, abscess, anal ulcer or stricture, or fissure). [44] Nearly 20-23% of patients with large bowel or small bowel disease have perianal complications, which may precede the development of intestinal symptoms and manifest as simple skin tags, anal fissures, perianal fistulae, or abscesses. [1] Symptoms may occur without involvement in any other area of the GI tract.

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Physical Examination

The physical examination should focus on temperature, weight, nutritional status, the presence of abdominal tenderness or a mass, perianal and rectal examination findings, and extraintestinal manifestations (EIMs). Vital signs are usually normal in patients with Crohn disease, though tachycardia may be present in anemic or dehydrated patients. Chronic intermittent fever is a common presenting sign.

Abdominal findings may vary from normal to those of an acute abdomen. Diffuse abdominal tenderness or localized pain may be present. Fullness or a discrete mass may be appreciated, typically in the right lower quadrant of the abdomen (which is usual with ileal involvement), or a mass may be felt secondary to thickened or matted loops of inflamed bowel.

The perineum should be inspected in all patients who present with signs and symptoms of Crohn disease because abnormalities detectable in this region substantially increase the clinical suspicion of inflammatory bowel disease (IBD). Inspection of the perianal region can reveal skin tags, fistulae, ulcers, abscesses, and scarring. A rectal examination can help to determine sphincter tone and aid in detecting gross abnormalities of the rectal mucosa or the presence of hematochezia.

In addition to local complications, various EIMs may be associated with Crohn disease, usually involving the skin, joints, mouth, eyes, liver, or bile ducts. [45] The most common EIMs are arthritis and arthralgia. The large joints (eg, hips, knees, ankles) are typically involved. [6]

Examination of the skin and oral mucosa may show mucocutaneous or aphthous ulcers, erythema nodosum, and pyoderma gangrenosum. Skin examination may also reveal pallor in patients with anemia or jaundice in those with concomitant liver disease with cholestasis. Eye examination may reveal episcleritis. For the diagnosis of uveitis, a slit-lamp examination by an experienced physician is necessary.

Careful assessment of growth and development is an important part of evaluating pediatric patients. Growth abnormalities may be detected by evaluating the following parameters:

  • Height and weight
  • Height and weight percentiles for the patient’s age, as well as weight percentile for the patient’s height
  • Growth velocity
  • Body composition on anthropometry
  • Skeletal bone age

The most sensitive indicator of growth abnormalities in children is a decrease in growth velocity, which may be observed before the major percentile lines on standard growth curves are crossed. Decreased height velocity before the onset of intestinal symptoms can be observed in as many as 46% of patients with Tanner stage 1 or 2 development. Height at maturity is often compromised. Pubertal delay may precede the onset of intestinal symptoms, and accurate Tanner staging should be a part of routine physical examination.

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Intestinal Manifestations

The major intestinal complications of Crohn disease are due to the transmural nature of the disease, which leads to the formation of abscesses, fistulae, sinus tracts (incomplete fistulae ending in a cul-de-sac), strictures, and adhesions. These features may also contribute to bowel obstruction.

Microperforation typically occurs into other segments of bowel, leading to fistulae, or into areas such as the retroperitoneum, resulting in abscess formation. Perianal and perirectal fistulae occur in approximately 20-23% of individuals. Other complications of fistulizing disease include enterovesical, enterocutaneous, and rectovaginal fistulae, as well as extension into muscle in severe progressive cases.

Frank perforation is more uncommon, but it is one of the most serious complications of Crohn disease if it occurs. The presenting features of frank perforation are those of classic peritonitis, although these features can sometimes be masked by high-dose corticosteroid or immunosuppressant therapy.

Colonic malignancy is a clinically significant complication of Crohn disease with colonic involvement. Chronic inflammation is the conjectured etiology for the development of dysplasia followed by cancer. Most cases of colorectal cancer develop from early histologic lesions referred to as low-grade dysplasia (LGD) or dysplasia-associated lesion or mass (DALM). Sporadic adenomas can also progress to colon cancer. These are premalignant or precancerous lesions that progress to cancer via a pathway of inflammation and genetic mutations.

A meta-analysis revealed that the cumulative risk of colon cancer in Crohn disease approaches 3% at 10 years and 8% at 30 years. [46] It is widely known that individuals diagnosed at a younger age have a long disease duration (> 8 years), and that those with concomitant primary sclerosing cholangitis are at an increased risk for colorectal cancer.

The association of IBD with increased risk of colon cancer has led to North American consensus statements that recommend regular surveillance with colonoscopy every 1-3 years for those with either ulcerative colitis or colonic Crohn disease who have a disease duration longer than 8 years.

However, subsequent studies yielded different findings regarding the risk for colorectal cancer in people with Crohn disease. A population-based study did not show any temporal trends in colorectal cancer for Crohn disease, nor did it find an increased risk of such cancer in patients with this condition as compared with the general population. [47] In contrast, a health maintenance organization (HMO) study from Northern California found a 60% increased relative risk of colorectal cancer, which did not change over a 12-year period. [48]

Overall, with the advent of new technology (eg, chromoendoscopy) and the accumulation of evidence for the use of chemoprophylactic agents (eg, 5-aminosalicylic acid [5-ASA] and low-dose ursodiol), it appears that there may be a reduction in the risk for colorectal cancer in Crohn disease. At present, surveillance colonoscopy every 1-3 years remains the standard of care.

There is also a significant association between small bowel cancer and Crohn disease. However, the absolute risk is low. Future research may be helpful in clarifying incidence rates, duration and extent of disease, medication use, and other disease-modifying factors (eg, smoking) that may alter the risk stratification for small bowel cancer and Crohn disease.

Extraintestinal Manifestations (EIM)

EIMs may carry prognostic importance in Crohn disease.

Musculoskeletal disease

Musculoskeletal pain is considered the most common EIM of adult IBD, occurring in 9-53% of affected patients. [49, 50, 51] The differential diagnosis of this condition is vast and includes IBD-associated arthritides such as arthralgia (5-20%), ankylosing spondylitis (1-26%), psoriatic arthritis, reactive arthritis, and sacroiliitis, as well as fibromyalgia and osteoporosis and osteoporosis-related fractures.

The most common EIM in children and adolescents is arthritis (7-25% of pediatric patients), which may occur years before any GI symptoms develop and may persist after surgical or medical remission of the disease. The arthritis is usually seronegative, transient, and nondeforming; has an asymmetric distribution; and involves the large joints of the lower extremities.

In adults, the arthritis occurs when the disease is active and can affect large and small joints. Type 1 peripheral arthritis is pauciarticular (< 5 joints), and is strongly associated with IBD activity and other EIMs. The joint most commonly involved is the knee. Type 2 peripheral arthritis is polyarticular and independent of disease activity. The metacarpophalangeal (MCP) joint is the most commonly involved site; less frequently, the knees, ankles, shoulders, proximal interphalangeal (PIP) joint, and metatarsophalangeal (MTP) joint may be involved.

Dermatologic disease

Dermatologic EIMs occur in 2-34% of Crohn patients, with erythema nodosum the most common manifestation. Erythema nodosum is more common in Crohn disease than in ulcerative colitis and usually follows the course of the disease. This condition affects 3% of pediatric patients with Crohn disease and is less frequent than in adults. Approximately 75% of patients with erythema nodosum ultimately develop arthritis.

The lesions of erythema nodosum are raised, red, tender nodules that appear primarily on the anterior surfaces of the lower leg. These ulcers can be either solitary or multiple and either unilateral or bilateral, and they can range in size from several centimeters to distribution along an entire limb.

Although pyoderma gangrenosum is uncommon in Crohn disease, it may occur, even when the disease is in remission: 50% of patients will develop the rash despite quiescent Crohn disease activity. Therefore, medical therapy for the underlying bowel disease is not always successful. Consultation with a dermatologist may be necessary.

Other dermatologic manifestations include the following:

  • Sweet syndrome
  • Orofacial granulomatosis
  • Angular and aphthous stomatitis
  • Acrodermatitis enteropathica
  • Alopecia
  • Metastatic Crohn disease
  • Crohn disease of the vulva and penis
  • Psoriasis

Oral lesions

Aphthous ulceration in the mouth is the most common oral manifestation of Crohn disease, and it is commonly associated with skin and joint lesions. Oral lesions appear to parallel intestinal disease in most cases, but they may also develop before any GI symptoms occur.

Ophthalmologic disease

Ophthalmologic manifestations of Crohn disease (primarily episcleritis and anterior uveitis) most frequently occur when the disease is active. The rate of such manifestations is 0.5-5% in the adult population but is lower in children and adolescents.

The most common ocular manifestation is episcleritis, or inflammation of the vascular-rich episclera. Episcleritis should be suspected in patients who present with acute redness in one or both eyes, irritation, and burning. Uveitis is usually symptomatic, causing pain or decreased visual acuity. Treatment for these ocular EIMs is geared toward controlling the underlying bowel disease.

Other manifestations may include increased intraocular pressure and cataracts in children who receive corticosteroid therapy. Conjunctivitis also occurs. All patients with Crohn disease require ophthalmologic examination at regular intervals.

Urologic disease

Urologic EIMs include nephrolithiasis, hydronephrosis, and enterovesical fistulae. The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts. Nephrolithiasis occurs in fewer than 5% of children with Crohn disease, usually as a result of the fat malabsorption that occurs with small bowel Crohn disease. Dietary calcium binds to malabsorbed fatty acids in the colonic lumen; therefore, free oxalate is absorbed. The absorption of free oxalate results in hyperoxaluria and oxalate stones.

Gallstones are formed as a consequence of an increased cholesterol concentration in the bile, caused by a reduced bile salt pool. In patients with an ileostomy, increased fluid and electrolyte losses may lead to concentrated acidic urine and the formation of uric acid stones. External compression of the ureter by an inflammatory mass or abscess may lead to hydronephrosis. Enterovesical fistulae may present with recurrent urinary tract infections or pneumaturia.

Hepatobiliary disease

Hepatobiliary disease is among the most common EIMs of Crohn disease and its therapies. Abnormal serum aminotransferase levels are common during the course of Crohn disease in children. Most aminotransferase elevations are transient and appear to relate to medications or disease activity. Aminotransferase elevations that persist for longer than 6 months should be investigated because the likelihood of serious liver disease is increased.

Both intrahepatic and extrahepatic manifestations of liver disease occur in children with Crohn disease. Intrahepatic manifestations include chronic active hepatitis, granulomatous hepatitis, amyloidosis, fatty liver, and pericholangitis. Extrahepatic manifestations include cholelithiasis and obstruction.

Cholelithiasis is more frequent in patients with IBD than in the general population, probably because of bile salt pool alteration from malabsorption. Chronic active hepatitis and sclerosing cholangitis develop in fewer than 1% of children with Crohn disease. Sometimes, a hepatic abscess manifests as fever of unexplained origin.

Primary sclerosing cholangitis is a progressive chronic liver condition of unknown etiology that increases the risk for cholangiocarcinoma and colorectal cancer in patients with IBD. Patients can be asymptomatic with mild elevations of transaminase and alkaline phosphatase, or they may present with advanced findings of cholangitis and jaundice. Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) typically reveals strictures of medium and large intrahepatic and extrahepatic bile ducts.

Primary sclerosing cholangitis has an established strong association with IBD, particularly ulcerative colitis. About 5-10% of patients with primary sclerosing cholangitis have Crohn disease, but only 2% of Crohn disease patients develop primary sclerosing cholangitis. There is a 2:1 male prevalence for the disorder.

The clinical course of primary sclerosing cholangitis does not parallel bowel disease, and this condition can develop in the years before or after the development of GI symptoms. Patients with this disease may require transplantation if cirrhosis develops or if severe recurrent cholangitis occurs.

Other pancreatic or hepatobiliary manifestations of Crohn disease include the following:

  • Cirrhosis related to long-standing primary sclerosing cholangitis
  • Portal vein thrombosis
  • Cholangiocarcinoma
  • Pancreatitis (idiopathic or drug-induced)

Thromboembolic disease

Thromboembolic disease is considered to be the result of a hypercoagulable state that parallels disease activity and is manifested by thrombocytosis, elevated plasma fibrinogen, factor V, factor VIII, and decreased plasma antithrombin III. This state may lead to deep vein thrombosis, pulmonary embolism, and neurovascular disease.

Compared with control subjects, patients with IBD have a 3-fold higher risk of thromboembolism. These patients have frequent exposure to classic thrombosis risk factors, including immobility, surgery, steroid therapy, and the presence of central venous catheters. Other factors that may play a role include smoking, antiphospholipid antibody syndrome, and hyperhomocystinemia.

Additional extraintestinal diseases

Bone metabolic disorders include osteopenia and osteoporosis. Hematologic manifestations include iron deficiency anemia, vitamin B-12 deficiency anemia, folate deficiency anemia, anemia of chronic disease, autoimmune hemolytic anemia, thrombocytosis, anemia due to GI bleeding, and thrombosis.

Genitourinary manifestations include nephrolithiasis, obstructive uropathy, glomerulonephritis, and amyloidosis. Pulmonary manifestations include granulomatous lung disease, fibrosing alveolitis, and pulmonary vasculitis. Cardiovascular manifestations include pericarditis, myocarditis, and vasculitis.

Malabsorption can occur as a result of loss of functional mucosal absorptive surface. This phenomenon can lead to protein-calorie malnutrition, dehydration, and multiple nutrient deficiencies. Involvement of the terminal ileum may result in malabsorption of bile acids, which leads to steatorrhea, fat-soluble vitamin deficiency, and gallstone formation.

Fat malabsorption, by trapping calcium, may result in increased oxalate excretion (normally complexed by calcium), causing kidney stone formation. Steatorrhea and fat-soluble vitamin deficiency may also lead to clotting abnormalities, calcium deficiency, and osteomalacia, which may progress to osteoporosis. Vitamin B-12 deficiency may also occur with ileal resection or long-standing ileal disease. [1]

Disease Classification and Activity Scoring Systems

A system to homogenize the classification of IBD on the basis of disease location and behavior was first established in 1998 in Vienna, Austria. [52] Further developments in the field were reviewed, and the Montreal revision of the Vienna classification was proposed (see below), with special attention to predominant parameters of age at diagnosis, location, and behavior of disease. [53]

Montreal classification system

The Montreal revision of the Vienna system is based on the following 3 variables:

  • Age at diagnosis
  • Disease distribution/location
  • Disease behavior

Age at diagnosis (A) has 3 categories, as follows [53] :

  • A1 – ≤ 16 years
  • A2 – 17-40 years
  • A3 – > 40 years

Disease distribution/location (L) has the following 4 categories, 1 of which is a modifier for upper GI involvement [53] :

  • L1 – Ileal
  • L2 – Colonic
  • L3 – Ileocolonic
  • L4 – Isolated upper GI disease; L4 is a modifier that can be added to L1-L3 when there is concomitant upper GI involvement

Disease behavior (B) has 1 interim category (B1) and 2 specified categories, with an additional modifier for perianal diseases (p), as follows [53] :

  • B1 – Nonstricturing, nonpenetrating; B1p: nonstricturing, nonpenetrating with perianal involvement
  • B2 – Stricturing; B2p: stricturing with perianal involvement
  • B3 – Penetrating; B3p: penetrating with perianal involvement

Crohn disease activity indices

Multiple scoring systems incorporating the patient’s history, physical examination findings, and laboratory data have been developed to assess disease activity in adults with Crohn disease. These scoring systems are used principally for assessing the efficacy of treatment and evaluating new therapies for research purposes.

One such index is the Crohn Disease Activity Index (CDAI), which was developed for use in adults. The Pediatric Crohn Disease Activity Index (PCDAI) was developed and validated in 1990; the results are correlated with the physician’s global assessment and with the Harvey-Bradshaw index (HBI), and they have significant interobserver reliability. The important difference between the PCDAI and the CDAI is the inclusion of growth parameters in the PCDAI score.

A modified PCDAI (Mod PCDAI), consisting of the laboratory measures of the PCDAI plus the C-reactive protein (CRP) level, has been shown to correlate with the PCDAI, the physician’s assessment, and fecal calprotectin. [54] This modified index can be used as an alternative to the PCDAI, with the advantage of having additional objective laboratory values embedded in it. [54] Other authors have described a short PCDAI. [55]

Other activity indices and their parameters used for clinical and research purposes include the following:

  • HBI – General well-being, abdominal pain, number of liquid stools per day, presence of abdominal masses, and complications or EIMs
  • Seo index – General well-being, amount of blood in stool, number of bowel movements during the day and the night, urgency of defecation, and number of extracolonic manifestations
  • Perianal Crohn Disease Index (PDAI) – Perianal discharge, pain with restriction of daily activities, restriction of sexual activity, physician scoring of the type and number of perianal disease, and presence of induration
  • Fistula Drainage Assessment – Fistula healing, ranging from heavy drainage or abscess to complete closure
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