Complications
Develops due to bowel wall thickening by acute inflammation. Presents with abdominal pain, nausea, vomiting, abdominal distension, and dilated bowel loops and air-fluid levels on x-ray.
Treatment involves bowel rest with nasogastric suctioning and may require corticosteroid therapy. Patients not responding to these measures require surgical resection, or for short segment strictures ≤4 cm, endoscopic dilation may be attempted. Endoscopic balloon dilation has substantial efficacy in both the short and the long term, and has an acceptable complication rate.[285][286]
Small bowel strictures may be treated by resection or strictureplasty. Strictureplasty has been shown to be a safe alternative to resection when the strictures are <10 cm in length.[195][196] Longer strictures are treated with non-conventional strictureplasty in some centres.[197] There is an incidence of carcinoma at strictureplasty sites.[198] Long segments, multiple strictures in short segments, and patients with enough bowel length to avoid short-bowel syndrome may be better served by resection.
Colonic strictures are treated by segmental resection if the disease is localised. Strictures at either end of the colon may be treated by segmental resections and two anastomoses to avoid a stoma. Multiple strictures may necessitate subtotal or total proctocolectomy. Proctocolectomy has a lower recurrence rate than segmental resection but necessitates an end stoma.
Treatment of strictures with immunomodulatory drugs is under investigation.[110]
In general, medical treatment with immunosuppressants for Crohn's disease should continue during pregnancy as the benefits outweigh the risks of drugs.[150]
The major exception for this is methotrexate, as it is teratogenic, and can lead to skeletal abnormalities and even miscarriage.[149][150] If pregnancy is being considered, a 6-month washout period is needed.[150] A high-dose folic acid supplement is recommended from 3 months before conception to at least the 12th week of pregnancy.[299] This also applies to prospective fathers so spermatogenesis can return to normal.[202]
Immunosuppressed patients may be at risk of infective colitis superimposed on Crohn’s colitis or Clostridium difficile infection associated with antibiotic use.
The inflamed or obstructed bowel is fragile and may perforate. This may present as a localised peri- or para-colic abscess with severe abdominal pain and fever, or with signs and symptoms of peritonitis if there is a free perforation.
A localised abscess may be treated with antibiotics and radiologically guided drainage. It is likely that an enterocutaneous fistula will occur, but surgery may be avoided in the emergency setting.
Free perforation is a surgical emergency requiring abdominal toilet, intravenous antibiotics to cover bowel pathogens, and either diversion or resection.
Sinus tracts develop because of inflammation that involves the whole bowel wall. In contrast to fistulae, sinuses do not terminate in other epithelial-lined organs and may be complicated by a phlegmon or abscess.
Sinuses may require surgical management.[201]
Potentially lethal complication of colitis characterised by total or segmental non-obstructive colonic dilation associated with systemic toxicity. This is caused by excess inflammatory mediators and bacterial toxins released from the diseased colon.
The main goal of treatment of toxic megacolon is to reduce the severity of colitis by treating the underlying Crohn's disease. This involves the use of corticosteroids, antibiotics, and/or immunosuppressive agents (ciclosporin).
All patients should be evaluated by a surgical team for possible need for colectomy.
When there is <100 cm of functioning small bowel left, typically after surgical resection but also with a high intestinal fistula, then the absorptive capacity is likely to be insufficient for the patient’s requirements without parenteral nutrition. Fluid and electrolyte loss can be dramatic. The stomach and duodenum secrete 7 litres per day, of which 6 are re-absorbed in the small bowel in a mechanism linked to sodium transport.
Patients with Crohn's disease have an overall increased risk of cancer and have increased risk of colon adenocarcinoma.[289]
Inflammatory bowel disease (IBD)-related colorectal cancer accounts for around 2% of the annual colorectal cancer mortality and for 10% to 15% of the annual deaths in patients with IBD.[290] An increased risk of death (HR 1.45; 95% confidence interval [CI] 1.29 to 1.63) and worse 5-year survival in individuals aged <50 years, has been reported in IBD-related colorectal cancer compared with sporadic colorectal cancer. Risk factors for colorectal cancer in IBD include male sex, family history of colorectal cancer, and the presence of colonic strictures or primary sclerosing cholangitis.[290]
These patients also have an increased incidence of squamous cell carcinoma of the anus, small bowel cancers, lung cancer, and lymphoma.[289][291][292][293][294][295][296][297][298]
There is an incidence of carcinoma at strictureplasty sites.[198]
Develops in patients with severe disease due to increased absorption of oxalate, poor digestion of fats, acidosis, and dehydration.
Complications of methotrexate therapy include long-term hepatotoxicity.[301]
Before commencing methotrexate, it is important to measure full blood count and renal and liver function, and these should be monitored regularly while on treatment.
Complications of methotrexate therapy include the development of pulmonary fibrosis.
Thiopurine (e.g., azathioprine, mercaptopurine) use in inflammatory bowel disease treatment has been associated with higher risk of developing non-melanoma skin cancer, non-intestinal lymphoma, and genitourinary cancer.[289]
Decreased absorption of bile acids causes secretory diarrhoea. Furthermore, depletion of the bile salt pool leads to malabsorption of fat, steatorrhoea, and increased risk of gallstone formation. The inadequate absorption of fat leads to deficiency in fat-soluble vitamins (A, D, E, and K).
Steatorrhoea and diarrhoea can promote the development of both calcium oxalate and uric acid stones.
Severe ileal disease or ileal resections can lead to vitamin B12 malabsorption and deficiency requiring supplementation.[53]
Patients with Crohn's disease (CD) have an increased risk of osteoporosis due to corticosteroid therapy, malabsorption, and disease-related inflammation. Despite vitamin D deficiency due to malabsorption and potential dietary avoidance of dairy products, osteomalacia is much less common than osteoporosis in patients with CD.
Fracture risk should be evaluated in all patients prescribed oral corticosteroids.[287] A dual-energy x-ray absorptiometry scan is recommended in patients who are at a high risk for osteoporosis.[8]
Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements. There is some evidence that vitamin D may be beneficial in all patients with CD, but further research is needed.[288]
Exercise and cessation of smoking is recommended.[8]
Patients with established fractures should be treated with bisphosphonates.[202]
Serious adverse events of immunomodulators include overwhelming sepsis. Immunomodulators should never be started if there is any indication of sepsis. Certain viruses can be fatal in patients taking azathioprine, due to the drug's immunosuppressive effects. Previous exposure to common viruses, such as varicella zoster (chickenpox), may be checked by antibody testing prior to initiation of azathioprine. Patients should be instructed to avoid live vaccination (e.g., rubella, bacille Calmette-Guérin, and yellow fever).
Tumour necrosis factor (TNF)-alpha inhibitors are associated with increased risk of developing tuberculosis, and patients should be screened with a combination of history-taking, chest x-rays, an interferon-gamma release assay blood test, and/or a tuberculin skin test if deemed high risk.[113] Some patients on infliximab have shown increase in perioperative complications.[300] Reactivation of hepatitis B has been reported, with a theoretical risk of reactivation of hepatitis C; patients with Crohn's disease should be tested for serological markers of hepatitis B and hepatitis C before treatment is initiated.[116][117]
Septic complications including opportunistic infections increase up to 15-fold if TNF-alpha inhibitors are used in combination with other immunosuppressives.
Complications as a result of methotrexate can be severe, as it can cause profound myelosuppression.
Before commencing methotrexate, it is important to measure full blood count and renal and liver function, and these should be monitored regularly while on treatment.
Hepatic involvement may manifest as primary sclerosing cholangitis (PSC). A prevalence of 2% to 8% is noted among patients with inflammatory bowel disease.[8]
Crohn's disease (CD)-associated PSC usually does not respond to the treatment of CD, in which case ursodeoxycholic acid has a controversial benefit.
Steatotic liver disease is caused by malnutrition and corticosteroids.
Liver abscess presents with fever, abdominal pain, and jaundice. The mechanism of abscess formation is unclear. It may be due to direct extension of intra-abdominal infection or portal pyaemia seeding in the liver.
Granulomatous hepatitis is an uncommon complication.
Peripheral arthritis involves large joints. In addition, patients may have central or axial arthritis (sacroiliitis or ankylosing spondylitis) or undifferentiated spondyloarthropathy.
Treatment of arthropathy associated with Crohn's disease (CD) supports the short-term use of non-steroidal anti-inflammatory drugs (NSAIDs), local corticosteroid injections, and physiotherapy for peripheral arthritis, although the emphasis should be on treating the underlying CD.[202] Decision to use NSAIDs for the management of arthropathy should be made on a case-by-case basis.[8]
Patients with CD-associated arthropathy should be considered for treatment with methotrexate. The treatment is initiated intramuscularly, with an overlapping corticosteroid taper. Once a clinical response is achieved, methotrexate may be given orally, with an attempt to lower the dose gradually over several months. In addition, all patients should take folic acid per day in order to minimise the adverse effects of methotrexate.[145][147][161]
With axial arthropathy associated with CD, infliximab has been demonstrated to be effective in those with ankylosing spondylitis refractory or intolerant of NSAIDs.[253]
Ocular manifestations are relatively common with inflammatory bowel disease. Anterior uveitis is the most frequent manifestation.[8] Episcleritis, conjunctivitis, scleritis, optic neuritis, ischaemic optic neuropathy, other uveitis subtypes, central retinal vein occlusion, and orbital inflammation or myositis are less common.[8]
An expert opinion from an ophthalmologist is required when a diagnosis of uveitis is suspected. The first-line recommended treatment for anterior uveitis is topical ophthalmic corticosteroids.[8]
Skin disorders include: specific (metastatic Crohn's disease); reactive erythema nodosum, pyoderma gangrenosum, Sweet syndrome, oral lesions); associated (hidradenitis suppurativa, psoriasis); treatment-related (tumour necrosis factor [TNF]-alpha antagonist-induced skin lesions, drug hypersensitivities, skin cancer).[Figure caption and citation for the preceding image starts]: A patient's arms and hands show the presence of erythema nodosumCDC/ Margaret Renz [Citation ends].
Involvement of a dermatologist in the early stages is recommended.[8]
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