Crohn's Disease: Causes, Symptoms, and Treatment

Crohn`s disease and ulcerative colitis are distinct clinical entities collectively referred to as "inflammatory bowel disease" (IBD). Crohn`s disease is an immunologically mediated inflammatory gastrointestinal condition, with pathology involving the entire thickness of the bowel wall.

How common is Crohn`s disease? 

Crohn`s disease is most commonly seen in North America, Northern Europe, and New Zealand with the onset occurring most frequently between ages 15 and 30 and 40 and 60. Experts estimate that more than three-quarters of a million people in the U.S. have Crohn’s disease. It affects approximately 6 to 8 million people globally. 

What are the causes of Crohn`s disease? 

The exact cause of Crohn`s disease is unknown. Substantial evidence suggests that the condition may result from an inappropriate immune response to environmental antigens like drugs, toxins, infections, or intestinal microbes in a genetically susceptible host. Large-scale genome studies have identified over 200 IBD-associated genes and more than 71 Crohn disease–susceptibility loci.

Genetic variants are associated with certain Crohn disease phenotypes. For example, NOD2/CARD15 mutations have been detected in patients with Crohn disease presenting with ileal involvement and increased severity at a younger age. These individuals often require surgical intervention.

What is the pathophysiology of Crohn`s disease?

The excessive immune response arises from innate and acquired mechanisms involving intestinal macrophages, neutrophils, and helper T-cells (T_h), promoting proinflammatory mediators like tumour necrosis factor-α (TNF-α). T_h1 and T_h17 are crucial mediators in the Crohn disease inflammatory cascade. Colonic Crohn lesions were found to have high levels of cytokines like interferon-γ and interleukins (ILs) 2, 12, and 18. (https://www.ncbi.nlm.nih.gov/books/NBK436021/)

What are the types of Crohn`s disease?

Crohn`s disease can involve any part of the digestive tract between mouth and anus. Inflammation is most commonly seen in the small and/or large intestines. Types of Crohn’s disease include:

• Ileocolitis: it is the most common type affecting the lower small intestine and part of your large intestine.
• Colitis: Inflammation found in the lining of the large intestine.
• Ileitis: Swelling and inflammation seen in the small intestine (ileum).
• Gastroduodenal: Inflammation and irritation affects the stomach and the top of the small intestine (the duodenum).
• Jejunitis: Patchy areas of inflammation seen in the upper half of the small intestine (the jejunum).
• Perianal disease: A portion of people have inflammation around the anus, which can cause fistulas and abscesses. 
• Extraintestinal manifestations of Crohn`s disease include: 
  • Eyes (episcleritis, scleritis, uveitis)
  • Mouth (stomatitis, aphthous ulcers)
  • Liver (gallstones, cholangitis, primary sclerosing cholangitis)
  • Kidneys (nephrolithiasis, hydronephrosis, urinary tract infections)
  • Joints: axial (ankylosing spondylitis) or peripheral (knees, ankles, wrists, elbows) arthritis
  • Skin (erythema nodosum and pyoderma gangrenosum) 

What are the symptoms of Crohn`s disease?

Symptoms of Crohn`s disease may come on gradually or suddenly and they may be mild to severe. 

• Abdominal pain or cramps
• Chronic diarrhoea (watery stool)
• Loss of appetite and weight loss
• Bloody stool (rectal bleeding) 
• Mouth ulcers or pain in mouth or gums
• Fever and fatigue (tiredness that doesn’t improve with rest)
• Abscesses of infections around your anal canal.

Symptoms of other systems involvement include:

• Arthritis or joint pain
• Rashes
• Eye inflammation, such as uveitis or episcleritis
• Kidney stones
• Osteoporosis (loss of bone mass)
• Skin tags (usually around your anus)
• Inflammation in bile ducts
• Crohn’s disease in children can cause growth delays or failure to grow properly 

Complications of Crohn`s disease include abscesses, anal fissures, fistulas, bowel obstruction, colon cancer, blood clots, malnutrition and anaemia. (https://my.clevelandclinic.org/health/diseases/9357-crohns-disease) 

How is Crohn`s disease diagnosed?

A thorough abdominal assessment will be part of physical examination, along with vital signs assessment which may reveal fever, tachycardia, and hypotension. Your physician may also examine the skin, musculoskeletal, renal and neurological systems to find extraintestinal manifestations of Crohn`s disease. 

Laboratory tests include:

• Stool tests to rule out infections include culture and sensitivities, ovum and parasites, and C. difficile toxins. Stool calprotectin can detect active Crohn disease and is used for monitoring disease activity.
• Blood tests may reveal anaemia (due to vitamin B12 or iron deficiency) and liver disease. Electrolytes may be deranged due to diarrhoea. Increased creatinine, blood urea nitrogen, and liver enzymes may indicate renal and liver involvement, respectively.

C-reactive protein (CRP) or erythrocyte sedimentary rate elevation may reflect inflammation severity.

• Urinalysis may reveal bacteriuria and leukocyturia. 

Imaging 

• X-ray can detect bowel obstruction. Small bowel follow-through is often used to assess terminal ileal involvement. 
• Abdominal and pelvic computed tomography (CT), magnetic resonance imaging (MRI), or enterography (MRE) can detect abscesses, strictures, and fistulisation (see Image. Crohn Disease on Computed Tomography). Both give clearer images of the diseased intestine. However, MRI can provide more detail when investigating fistulizing disease. Additionally, MRI is preferable over CT in paediatric populations, as it emanates little ionizing radiation.
• The bowel mucosa may be visualized by upper endoscopy and colonoscopy. Additionally, these modalities permit the assessment of the extent of bowel inflammation and tissue sample collection for disease confirmation. Endoscopic evaluation is also useful for assessing treatment response. (https://www.ncbi.nlm.nih.gov/books/NBK436021/) 

Ultrasound does not pose a radiation risk and is widely available, though the image may not have good resolution. Features that may be appreciated using this modality include fistulae, free intraperitoneal fluid, abscess formation, and increased superior mesenteric artery flow. The superior mesenteric artery often has increased flow volume during active disease that may be documented by Doppler ultrasound. 

How is Crohn`s disease treated?

Currently, there is no cure for Crohn`s disease and treatment options are aimed at symptom relief. As, symptoms vary across the individuals, there are multiple options to choose from:

Anti-inflammatory medication

• Short-term use of Corticosteroids such as prednisone and budesonide (Entocort EC) can help reduce inflammation in the body. 
• For mild to moderate Crohn`s disease involving the colon, oral 5-aminosalicylates such as sulfasalazine (Azulfidine), which contains sulfa, and mesalamine (Delzicol, Pentasa, others) may help. 

Immune system suppressors

• Azathioprine (Azasan, Imuran) and mercaptopurine (Purinethol, Purixan) are widely used immunosuppressants unlike methotrexate which only chosen if the patient does not respond to other drugs.

Biologics

• Tumour necrosis factor inhibitors such as Infliximab (Remicade), adalimumab (Humira) and certolizumab pegol (Cimzia) work by neutralizing an immune system protein known as tumour necrosis factor (TNF).
• Ustekinumab (Stelara) interferes with the action of an interleukin, which is a protein involved in inflammation.
• Vedolizumab (Entyvio), a monoclonal antibody works by stopping certain immune cell molecules — integrins — from binding to other cells in the intestinal lining.
• Risankizumab (Skyrizi) is another monoclonal antibody which acts against a molecule known as interleukin-23, one of the inflammation mediators. 

Janus kinase inhibitors

Taken orally, these newer medicines help reduce inflammation by targeting parts of the immune system that cause inflammation in the intestines. 

Antibiotics

Antibiotics can reduce the amount of drainage from fistulas and abscesses and sometimes heal them in people with Crohn's disease. Some researchers also think that antibiotics help reduce harmful bacteria that may be causing inflammation in the intestine. Commonly prescribed antibiotics include ciprofloxacin (Cipro) and metronidazole (Flagyl).

In addition to controlling inflammation, some medications like anti-diarrheal, pain relievers and supplemental vitamins may provide symptomatic relief. 

Surgery

If diet and lifestyle changes, medicines, or other treatments don't relieve symptoms, a healthcare professional may recommend surgery. 

During surgery, the surgeon removes a damaged portion of your digestive tract and then reconnects the healthy sections. Surgery also may be used to close fistulas and drain abscesses. The best approach is to follow surgery with medicine to reduce the risk of recurrence. (https://www.mayoclinic.org/diseases-conditions/crohns-disease/diagnosis-treatment/drc-20353309)