Crohn’s disease (CD) is a chronic idiopathic inflammatory bowel disease, with a complex aetiology involving genetic, environmental, and immunological factors. It is characterised by recurring episodes of inflammation, ulcerations, and strictures, leading to a wide range of symptoms and complications.
An interview with Theresa Lowry Lehnen, RGN, RNP, PhD, Clinical Nurse Specialist and Associate Lecturer with South East Technological University
Over 40,000 people in Ireland are living with inflammatory bowel disease (IBD). Of these approximately 20,000 people are affected by colitis and Crohn’s Disease. Crohn’s disease can affect people of any age but usually starts between the ages of 15 and 35, while a second smaller peak can occur from the ages of 50s to 70s. CD affects men and women equally, with a slight female predominance in adult onset Crohn’s disease. Incidence and prevalence are higher in high income countries and in urban areas, with a high incidence in Northern Europeans and among the Ashkenazi Jewish population. IBD is complex and costly, and its increasing prevalence places a greater stress on health care systems.
We spoke with Theresa Lowry Lehnen, Clinical Nurse Practitioner and Associate Lecturer South East Technological University to find out more about the diagnosis, management and outlook for this condition.
Theresa told us, “Crohn’s disease can affect any part of the gastrointestinal tract. 50% of patients have terminal ileum and colon involvement, while 30% have small-bowel only involvement, and 20% of cases are isolated to the colon. In addition, 25% of patients experience perianal complications including fissures and fistula. Less frequently (<10%), patients present with isolated perianal complaints, upper gastrointestinal disease, or extra intestinal manifestations (EIMs) which can affect the skin, joints, eyes, liver, blood vessels, and kidneys. Arthritis is the most common EIM affecting up to 25% of patients with CD. There is no cure and most patients experience bouts of remissions and relapse at unpredictable times.
“In Crohn’s disease, the inflammation extends through the entire thickness of the bowel wall from the mucosa to the serosa. The disease runs a relapsing and remitting course. With multiple relapses, it can progress from an initially mild or moderate inflammatory condition to a severe penetrating and stricturing disease. CD has a significant impact on the quality of life of affected individuals, necessitating early diagnosis and appropriate management strategies.”
Pathophysiology
The pathophysiology of Crohn’s disease is multifactorial in nature, involving genetic predisposition, infectious, immunological, environmental, and dietary factors. Theresa adds, “A major role is played by alterations at the level of immunity and inflammation. Innate immunity is involved in terms of defects in the mucous barrier (MUT2 and FUT2 genes) while adaptive immunity relies on a TH1 lymphocytic response and TREG cells mediated by cytokines like TNF-α, IL-12, IL-34 and IL-23. The increased migration to the sites of inflammation is also determined by a reshaping of the extracellular matrix through the action of metalloproteins MMP-1 and MMP-3 and the overexpression of adhesions molecules such as MAcCAM-1 and integrin α4β4.
“The characteristic transmural inflammation can include the entire GI tract from mouth to the perianal area; although it most frequently involves the terminal ileum and right colon. The initial lesion starts out as an infiltrate around an intestinal crypt. This leads on to ulceration first in the superficial mucosa and then the deeper layers.
“As the inflammation progresses, non-caseating granulomas form involving all layers of the intestinal wall. It can develop into the classic cobblestone mucosal appearances and skip lesions along the length of the intestine sparing areas with normal mucosa. As the flare of Crohn settles, scarring replaces the inflamed areas of the intestines. Granuloma formation is very common in Crohn’s disease but absence does not exclude the diagnosis. Ongoing inflammation and scarring can lead to bowel obstruction and stricture formation. Crohn’s disease is also associated with enterovesical, enteroenteral, enterocutaneous, and enterovaginal fistulas.”
Risk Factors
Environmental factors can include smoking, antibiotics, nonsteroidal anti-inflammatory drugs and reduced fibre diet. Theresa notes that while the role these factors play is not fully known, they can act as triggers to initiate a harmful immune response in the GI tract.
“Smoking is the most notable risk factor for developing Crohn’s disease, aside from family history and ethnic background. Smokers are twice as likely to develop Crohn’s compared to nonsmokers, and those who smoke usually experience more severe symptoms compared to those with the condition who do not smoke,” she says.
“While there is no evidence that diet plays a role in Crohn’s disease, certain types of food and drink have been associated with worsening symptoms including milk, dairy products, alcohol, processed, spicy and fatty foods. There is no diet or eating plan that will work for everyone with Crohn’s disease and dietary recommendations must be tailored individually. Some research suggests that a Mediterranean style diet is associated with an improved quality of life and reduced disease activity in Crohn’s disease. Some probiotics have also demonstrated small benefits. Although flares are often associated with stressful events, there is no evidence to prove that stress causes or contributes to Crohn’s disease.”
There are 3 main phenotypes of CD: inflammatory, stricturing, and penetrating. Presenting symptoms are variable and some patients may have symptoms for years before a diagnosis of Crohn’s disease is made. Patients with inflammatory disease often present with abdominal pain and diarrhoea, and may develop more systemic symptoms including weight loss, low-grade fevers, and fatigue. Patients with stricturing disease may develop bowel obstructions while those with penetrating CD can develop fistula or abscesses. When an abscess is present, in addition to abdominal pain, patients can have systemic symptoms such as fever and chills and may also present with signs of acute peritonitis.
“The diagnosis of Crohn’s disease can be quite challenging given that presenting symptoms can be insidious and nonspecific,” she says. “A detailed patient medical history and physical examination is carried out. Blood tests can highlight the presence of anaemia (B12 or iron deficiency) or liver disease. Special serology such as normal anti-neutrophil cytoplasmic antibodies (ANCA) and raised anti-saccharomyces cerevisiae antibodies (ASCA) can distinguish Crohn’s disease from ulcerative colitis. C-reactive protein (CRP) or erythrocyte sedimentary rate (ESR) can reflect the severity of the inflammation. Stool tests to rule out infections include culture and sensitivities, ovum and parasites, clostridium difficile toxins, and leukocyte count. Stools for calprotectin can detect active Crohn’s disease and are also used for monitoring the illness. Plain x-rays are ordered if bowel obstruction is suspected. The perineum should be examined in all patients, and may reveal skin tags, ulcers, fistulas, scarring, and abscess. Frank perforation is rare but can be a presentation of Crohn’s disease.
“Symptoms that require further investigation include weight loss, bloody diarrhoea, iron deficiency, and night-time awakenings.
A significant family history of IBD, unexplained elevations in the C-reactive protein level, sedimentation rates, or other acute phase reactants such as ferritin and platelets, or low B12 should prompt further investigation.”
According to Theresa, there is no single test that can be used to confirm or disprove a diagnosis of Crohn’s disease.
“The diagnosis is made based on symptoms, endoscopic and radiologic findings. (Colonoscopy, Biopsy, SBE, CT, MRI, Wireless Capsule Endoscopy). Pathology can also be confirmatory. Endoscopy with histological evaluation remains the gold standard for diagnosing CD. However, advanced imaging techniques, such as magnetic resonance enterography (MRE) and computed tomography enterography (CTE), have emerged as valuable tools for evaluating disease extent and complications. Biomarkers, such as faecal calprotectin and C-reactive protein, aid in disease monitoring and predicting disease activity.”
Complications
Crohn’s disease is associated with extraintestinal manifestations including episcleritis, uveitis, stomatitis, aphthous ulcers, liver steatosis, gallstones, cholangitis, primary sclerosing cholangitis, nephrolithiasis, hydronephrosis, urinary tract infections, arthritis (sacral spine, knee, ankles, hips, wrist, elbows), ankylosing spondylitis, erythema nodosum, and pyoderma gangrenosum. Thromboembolic disease can be a complication of Crohn disease, and may present with deep vein thrombosis, stroke, or pulmonary embolism. Patients with Crohn’s disease have an increased risk for colorectal cancer.
Both Crohn’s Disease and Ulcerative Colitis (UC) are inflammatory bowel diseases (IBDs), but there are some key differences, see table below.
Treatment and Management
The diagnosis, treatment and management of Crohn’s disease requires a multi-professional team approach. Patient education regarding their illness is very important. There are several medications available to treat Crohn’s disease, however, there is no cure. The mainstay of treatment is medical therapy with the goal of achieving clinical, endoscopic and histologic remission, demonstrated by mucosal healing. Treatment is chosen based on the disease stage, severity and location. Dietician input and nutritional supplementation are highly recommended before and during the treatment of Crohn disease.
Theresa says, “Steroids are used to induce remission but are not an effective maintenance agent. Steroids are usually only used to treat the active disease because their long-term use is associated with a range of adverse side effects. Budesonide and prednisolone are two steroids that are often used to treat Crohn’s disease. Budesonide is usually the first choice of steroid prescribed to help control the symptoms of Crohn’s disease.
“Taken on a short-term basis of less than 12 weeks budesonide may cause acne, oedema of the face, hands, arms, feet and legs, mood changes, insomnia and indigestion. If taken for more than 12 weeks, budesonide may cause osteoporosis, increased vulnerability to infection, cataracts, muscle cramps and stiffness, and vitamin D and calcium supplements will be required to help protect against the effects of osteoporosis. Due to increased vulnerability to infections, close contact with people who are known to have infections, particularly those with chickenpox, measles and shingles should be avoided.
“Prednisolone is used in cases where budesonide proves ineffective. It has the same type of short and long-term side effects as budesonide, and has also been known to cause mental health problems in an estimated 5% of people.”
Sulfasalazine belongs to a group of medicines called aminosalicylates, known to reduce inflammation inside the colon. Theresa explains, “Sulfasalazine can be used as an alternative to steroids to treat mild cases of Crohn’s disease. Common side effects include headache, nausea, abdominal pain and diarrhoea. Immunosuppressants are used in maintenance therapy and in combination with steroids when a person has a relapse of symptoms. Immunosuppressants used for treating Crohn’s disease include methotrexate, azathioprine, tacrolimus and mercaptopurine. Side effects of azathioprine include increased vulnerability to infection, bleeding and bruising. Less common side effects include headaches, shortness of breath, dizziness, nausea and vomiting.
“Mercaptopurine originally developed to treat leukaemia has since proved effective in the treatment of Crohn’s disease. Given in tablet form, its side effects are not as severe as those associated with other forms of chemotherapy treatment. Common side effects include nausea and vomiting while less common side effects include loss of appetite, fatigue, breathlessness and weakness caused by anaemia. Effective contraception if sexually active is important while taking mercaptopurine, as it temporarily affects both ova and sperm and can increase the risk of birth defects.
“Biological therapies are a new type of medication created using naturally occurring biological substances, such as antibodies and enzymes. Two main biological therapies are infliximab and adalimumab.mumab can cause reactivation of the hepatitis B virus and may not be suitable for people who were previously infected. Common side effects of adalimumab include pain, swelling, redness and itching at the site of the injection, headache, and abdominal pain, nausea, vomiting, skin rash, muscle, joint and bone pain and respiratory tract infections, such as colds and pneumonia.”
“Infliximab works by targeting the tumour necrosis factor (TNF) antibodies that are responsible for much of the inflammation associated with Crohn’s disease. Given by intravenous infusion, around one in four people has an allergic reaction to infliximab and experiences symptoms such as joint and muscle pain, itchy skin, high temperature, rash, swelling of the hands and/or lips, problems swallowing and headaches. Symptoms range from mild to severe and usually develop in the first two hours after the infusion has finished.
“Adalimumab works in a similar way to infliximab by targeting TNF antibodies. It is given by injection and most people will need to have an injection every two weeks. Like infliximab, adalimumab increases vulnerability to infection, and those taking it should avoid contact with people with chickenpox or shingles and always report any symptoms of a possible infection to their GP. Adalimumab can cause reactivation of the hepatitis B virus and may not be suitable for people who were previously infected. Common side effects of adalimumab include pain, swelling, redness and itching at the site of the injection, headache, and abdominal pain, nausea, vomiting, skin rash, muscle, joint and bone pain and respiratory tract infections, such as colds and pneumonia.”
Theresa told us that the goal of medication management is to control the inflammation and induce a clinical remission with pharmacological therapy, however, most patients will eventually require surgery. Surgery is not curative, and patients still require ongoing therapy even after surgery for disease recurrence.
“Some people report complementary and alternative medicines (CAM) (including fish oils and probiotics) helpful in controlling certain symptoms of Crohn’s disease, however, there is little scientific data to support their effectiveness. Although many types of CAM are generally safe, issues of purity, contamination with toxic metals, lacing with prescription drugs, and the side effects of some traditional herbal remedies must be considered. Large well-designed RCTs are needed to validate specific CAM therapies, before they can be incorporated into evidence based medical treatments” she concluded.
