- Crohn’s disease
- Can You Die from Crohn’s Disease?
- 7 Complications of Untreated Crohn’s Disease
- 1. Bowel obstruction
- 2. Malnutrition
- 3. Ulcers
- 4. Fistulas
- 5. Colon cancer
- 6. Arthritis
- 7. Osteoporosis
- The Takeaway
- Fatal Staphylococcal Sepsis in Crohn’s Disease After Infliximab
- Case Report
- Author notes
- What are the stages of Crohn’s disease?
Surgical operations can be a very important part of the treatment of Crohn’s disease. The main reason for needing surgery is to remove thickened blocked segments of the intestine which medicines are usually unable to tackle. The surgical removal of the affected intestine usually works very well, results in few problems post-operatively and restores full health quickly. Surgery is also usually carried out when badly affected parts of the intestine have caused an abscess or fistula in the abdomen or in the perianal area. An operation can sometimes also be the best option when severe Crohn’s disease is not responding to drug treatment. Occasionally, colonoscopy with special dilating balloons can be used to open up narrowed sections.
- Stoma surgery: many people presume that surgery for Crohn’s disease means having a permanent stoma bag. In fact, stomas (ileostomy or colostomy) if used, will often be temporary. After a section of affected intestine has been removed, a very delicate join (or ‘anastomosis’) is made between the unaffected ends of the intestine. In order to protect this join while it heals, the surgeon will then create a temporary stoma, which is then taken away at a second, smaller operation a few months later. This happens particularly when someone is underweight or taking steroids which reduce the ability of body tissues to heal.
Can You Die from Crohn’s Disease?
Although Crohn’s disease is a chronic illness with episodes of remission and relapses, appropriate medical and surgical therapies help affected individuals have a reasonable quality of life.
- Crohn’s disease usually has a chronic, slow course regardless of the site of involvement.
- Medical therapy becomes less effective with time. Nearly two thirds of people with Crohn’s disease require surgery for complications at some point in their disease.
- The longer a person has Crohn’s disease, the more likely they are to develop complications that can be fatal. Cancer of the digestive tract is the leading cause of death for people with Crohn’s disease.
- Crohn’s disease frequently recurs after surgery.
Patients will need to visit their health-care professional regularly so that the patient’s medical condition can be monitored, determine how well treatment is working, and check for relapse and return of symptoms. The intestinal complications of Crohn’s disease include:
- Intestinal obstruction
- Hemorrhage (bleeding) – Unusual in Crohn’s disease
- Malabsorption – Results in diarrhea and nutritional deficiencies
- Acute regional enteritis
- Carcinoma – Colonic disease increases risk of colon cancer
For more information, read our full medical article about Crohn’s disease.
7 Complications of Untreated Crohn’s Disease
Crohn’s disease (CD) is an inflammatory bowel disease that can affect any part of the gastrointestinal tract, but most often affects the end of the small intestine (ileum), the colon, or both.
Your immune system fights infection by producing a protein known as tumor necrosis factor (TNF). If you have Crohn’s disease, your body produces too much TNF, which causes your immune system to overreact and attack the wrong things. The result is inflammation that can lead to Crohn’s symptoms.
There is no cure for Crohn’s, but you can work toward disease remission with effective treatment. Not treating Crohn’s allows the disease to progress. To be effective, your Crohn’s treatment should be consistent. If it’s not, complications can result. So, it’s important to stick with a healthy diet and continue taking your medication even when you are feeling well.
Here are seven complications associated with untreated Crohn’s disease.
1. Bowel obstruction
A bowel obstruction occurs when intestinal contents are partially or fully blocked and unable to move. There are several ways that this can occur in people with Crohn’s disease:
- Inflammation can thicken the intestinal walls enough to narrow or even close off the intestinal tract.
- Strictures can cause bowel obstructions. A stricture, or stenosis, is an area of the gastrointestinal tract that has been narrowed by scar tissue caused by repeated bouts of inflammation.
- Adhesions, or strips of fibrous tissue that cause organs and tissues to bind together, can block the intestinal tract.
Proper nutrition is critical for good health. Your digestive tract is a key site of nutrient absorption. Chronic inflammation in your bowels can interfere with your body’s ability to absorb vitamins and minerals from the foods you eat. Chronic inflammation caused by Crohn’s disease may also suppress your appetite. This may prevent you from ingesting the nutrients you need to stay healthy.
There are a number of significant issues caused by malnutrition, including anemia caused by a deficiency in iron or vitamin B-12. This is common in people with Crohn’s disease. Other issues caused by not getting adequate nutrients include:
- reduced immune system function
- muscular deterioration that causes issues like decreased coordination or heart failure
- kidney malfunction
- neurological issues like depression and reduced cognitive function
Ulcers are open sores that can appear anywhere in your digestive system. They can be painful and dangerous if they cause internal bleeding. They can also cause perforations, or holes, in the intestinal tract. This may allow digestive contents to enter the abdominal cavity. If this occurs, it requires immediate medical attention.
Ulcers that go completely through the digestive tract wall can create fistulas, or connections to other body parts. This allows digestive material to leak into the bowel and enter whatever area it’s connected to, such as the bladder or uterus.
5. Colon cancer
If you have the increased inflammation associated with Crohn’s disease, you also have a higher risk for colon cancer. Precancerous cells can develop in the inflamed areas. Your risk increases if you were diagnosed with Crohn’s disease before the age of 30. This is because you’ve had more exposure to inflammation. Ask your doctor how often you should get a colonoscopy to check for colon cancer.
You are living with chronic inflammation if your Crohn’s disease is untreated. Experts believe a prolonged inflammatory response can trigger a similar reaction in joints and tendons, leading to enteropathic arthritis. This type of arthritis usually affects the joints in your limbs and sometimes your spine. Approximately 20 percent of people with inflammatory bowel disease develop enteropathic arthritis.
Crohn’s-related issues that contribute to weakened bones include:
- impaired nutrient absorption
- physical discomfort that keeps you from being active
Part of your Crohn’s treatment strategy should be to counteract these issues by making sure you ingest enough building nutrients like calcium and vitamin D. You should also do regular weight-bearing exercises.
Crohn’s disease doesn’t have a cure, but it is treatable. You can go into remission with targeted and consistent treatment. Without treatment, the chronic inflammation that exists causes the condition to progress and produce complications. If you have concerns about treatment, talk to your doctor. The more information you have, the better equipped you’ll be to make the best treatment choices.
Fatal Staphylococcal Sepsis in Crohn’s Disease After Infliximab
We report a case of a 40-year-old woman who had received infliximab for perianal Crohn‘s disease. After six infusions of infliximab, the patient developed staphyloccocal pneumonia resulting in fatal adult respiratory distress syndrome. The case is discussed in the context of the toxicity profile of infliximab.
Infliximab, a chimeric human-murine monoclonal antibody against tumor-necrosis factor alpha, has proven to be effective in inducing response in active Crohn’s disease 1 and rheumatoid arthritis. 2 Several severe infectious complications have been observed including tuberculosis, 3 listeriosis, 4 histoplasmosis, 5,6 and aspergillosis. 7 Here we report a case of a lethal staphylococcal sepsis in a patient treated with infliximab for fistulous Crohn’s disease.
A 40-year-old woman with a 23-year history of Crohn’s disease presented in October 2002 in a regional hospital with multiple draining fistulas in the anogenital region with inflammatory infiltration and induration of the skin. Partial colonoscopy revealed multiple ulcers in sigmoid and the descending colon typical for Crohn’s disease. The transverse colon showed a stenosis that could not be passed, but was subclinical. The patient’s former history included a colonic perforation 8 years ago due to Crohn’s disease. Until the actual admission the only medication had been mesalamine 3g/d.
After performing a negative skin test for tuberculosis and an unsuspicious chest x-ray a therapy with infliximab was started for perianal fistulation. After three infusions of infliximab, the patient presented again. Skin lesions in the anogenital region were improved; fistulas had ceased to drain. Colonoscopy showed mucosal healing of the former ulcerations but the stenosis of the transverse colon was still present. Treatment with infliximab was continued every 3 weeks.
After three additional infusions, the patient presented in February 2003 in a second hospital with fever, dyspnea, and coughing. Chest x-ray showed large pneumonic infiltrates affecting predominantly the right lung. Laboratory tests showed leucopenia (2000/mm3), a C-reactive protein of 85mg/l and laboratory signs of renal failure (creatinine 5.36mg/dl, urea 291mg/dl). Arterial blood gas analysis under 6 l oxygen revealed hyperventilation with severe hypoxemia and acidosis (pO2 56mmHg, pCO2 26mmHg, oxygen saturation 83.8%, pH 7.29).
An antibiotic treatment with moxifloxacin was started and the patient was transferred to the Intensive Care unit of our hospital. Laboratory controls had worsened and showed signs of severe sepsis and disseminated intravascular coagulation with thrombocytopenia (50.000/mm3), fibrinogenemia (482mg/dl) and low antithrombin-3 (45%). The C-reactive protein had raised to 11.9mg/dl. Chest x-ray showed beginning adult respiratory distress syndrome (Fig. 1). The patient was intubated and mechanic ventilation was started. Antibiotic treatment was intensified to include imipenem, vancomycin, and clarithromycin. Catecholamines were required to stabilize circulation and continous venovenous hemofiltration was started.
Blood cultures taken at our hospital showed growth of Staphylococcus aureus. Broncho-alveolar lavage also revealed gram positive bacteria with no signs of fungal infection or acid fast bacilli. Immunofluorescence from blood culture was negative for Pneumocystis carinii, polymerase chain reaction was negative for Chlamydia pneumoniae, mycoplasma pneumoniae and cytomegaly virus. Blood, urine and sputum cultures were negative for Mycobacterium tuberculosis, also.
Acute respiratory distress syndrome worsened and despite initiation of extracorporal membrane oxygenation the patient died eight days after admission to our hospital from respiratory failure. Autopsy revealed extensive bilateral pulmonary abscesses with gramnegative bacteria and alveolar hyaline membranes consistent with adult respiratory distress syndrome. At autopsy the colonic stenosis was no longer evident and there was no abscess or malignancy.
A multitude of opportunistic infections has been reported after treatment with antibodies against tumor necrosis factor. Evidence for 44 fatal complications following infliximab in Germany alone, 24 of the fatalities related to severe infections, has been published recently. 8 The treatment associated international casualties reported to the authorities have not been published but four deaths (0.7%) in the Accent I trial 9 as well as the 1–2% Remicade related deaths in the MAYO experience 10 also warn against too liberal use.
TNF-α is not only a key cytokine in the inflammatory process of inflammatory bowel diseases but it turns out that it is essential in host defense against various infectious agents as well. In addition to neutralizing soluble TNF infliximab is able to induce apoptosis in immune cells. 11 Latent tuberculosis is controlled by TNF probably through the apoptosis of bacillary infected macrophages. 12,13 An increasing number of fatal tuberculosis after treatment with infliximab has been reported. 13,–15 Similarly, the host defense against listeria monocytogenes seems to depend on an intact endogenous production of tumor necrosis factor 16 and fatal infections with this agent have been reported recently after treatment with infliximab. 4,17 TNF-α also has a central role in the pulmonary recruitment of neutrophilic response against Aspergillus fumigatus,18 a pathogen mainly affecting severe immunocompromised patients. Fatal aspergillosis in a young patient with Crohn’s disease without any additional immunosuppressive therapy apart from infliximab has been published recently. 7
To our knowledge the present case is the first report on a fatal infection with Staphylococcus aureus in a patient treated with infliximab. Our patient did not receive any additional immunosuppressive agents. The initial infectious agent leading to severe pneumonia was Staphylococcus aureus confirmed by blood culture and brochoalveolar lavage. Despite broad antibiotic therapy against gram-positive and negative bacteria autopsy revealed gram-negative abscess formation suggesting a complete break-down of host defense and underlines the risk of these anti-TNF-α strategies. Probably this patient‘s fistulae should have been treated with antibiotics like metronidazol and/or ciprofloxacine before starting infliximab. For security reasons prior MRI imaging to exclude an abscess before administration of infliximab should probably be recommended. 19 It is also possible that the relatively short 3-week treatment intervals have contributed to the toxicity. Anti-TNF-α treatment seems to substantially decrease the adequate host defense against bacterial agents and may lead to uncontrolled immunosuppression in some patients. Thus, the efficacy of infliximab has to be weighed against the increasing evidence for severe and sometimes fatal infectious complications. Considering the potential for lethal side effects and limited efficacy of infliximab in inducing and maintaining remission in nonperforating disease, 9 especially the long term treatment in Crohn‘s disease has to be critically assessed. Thus, in agreement with the German Consensus guidelines on Crohn’s disease, 20 infliximab should be restricted to otherwise therapy refractory patients, including the surgical options.
1. Targan SR , Hanauer SB , van Deventer SJ , et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med. 1997; 337:1029–1035. 2. Elliott MJ , Maini RN , Feldmann M , et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994;344:1105–1110. 3. Keane J , Gershon S , Wise RP , et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345:1098–1104. 4. Slifman NR , Gershon SK , Lee JH , et al. Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents. Arthritis Rheum. 2003;48:319–324. 5. Lee JH , Slifman NR , Gershon SK , et al. Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. Arthritis Rheum. 2002;46:2565–2570. 6. Wood KL , Hage CA , Knox KS , et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167:1279–1282. 7. Warris A , Bjorneklett A , Gaustad P . Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med. 2001;344:1099–1100. 8. Andus T , Stange EF , Hoffler D , et al. Med Klin. 2003;98:429–436. 9. Hanauer SB , Feagan BG , Lichtenstein GR , et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359: 1541–1549. 10. Colombel JF , Loftus E , Tremaine WJ , et al. The safety profile of infliximab for Crohn‘s disease in clinical practice: The Mayo Clinic experience in 500 patients. Gastroenterology 2003;124. 11. Van den Brande JM , Braat H , van den Brink GR , et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology. 2003;124:1774–1785. 12. Keane J , Remold HG , Kornfeld H . Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol. 2000;164:2016–2020. 13. Fratazzi C , Arbeit RD , Carini C , et al. Programmed cell death of Mycobacterium avium serovar 4-infected human macrophages prevents the mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages. J Immunol. 1997;158: 4320–4327. 14. Liberopoulos EN , Drosos AA , Elisaf MS . Exacerbation of tuberculosis enteritis after treatment with infliximab. Am J Med. 2002;113:615. 15. Vonkeman HE , van der Valk PD , Mulder L , et al. Ned Tijdschr Geneeskd. 2002;146: 1196–1199. 16. Nakane A , Minagawa T , Kato K . Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection. Infect Immun. 1988;56:2563–2569. 17. Gluck T , Linde HJ , Scholmerich J , et al. Anti-tumor necrosis factor therapy and Listeria monocytogenes infection: report of two cases. Arthritis Rheum. 2002;46:2255–2257. 18. Schelenz S , Smith DA , Bancroft GJ . Cytokine and chemokine responses following pulmonary challenge with Aspergillus fumigatus: obligatory role of TNF-alpha and GM-CSF in neutrophil recruitment. Med Mycol. 1999;37:183–194. 19. Van Assche G , Vanbeckevoort D , Bielen D , et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn‘s disease. Am J Gastroenterol. 2003;98:332–339. 20. Stange EF , Schreiber S , Folsch UR , et al. Z Gastroenterol. 2003;41:19–20.
Reprints: Klaus R. Herrlinger, MD, Department of Gastroentroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany Copyright © 2004 by Lippincott Williams & Wilkins.
What are the stages of Crohn’s disease?
Share on PinterestA doctor may prescribe drugs to treat the symptoms of Crohn’s disease.
Treatment of Crohn’s disease is different for everyone and aims to:
- reduce inflammation in the intestines
- relieve symptoms
- prevent flare-ups
- achieve and maintain remission
Treatment may change over time, and it is essential to seek medical advice for flare-ups.
Different medications are available to treat people with Crohn’s disease. A doctor will prescribe drugs based on how severe a person’s symptoms are and what type of Crohn’s disease they have.
Drug treatments include:
- Aminosalicylates, which doctors use to treat people with mild to moderate symptoms. These drugs help reduce inflammation in the intestines.
- Corticosteroids reduce inflammation by suppressing the immune system. Doctors prescribe these drugs for moderate to severe symptoms.
- Antibiotics can treat infections or complications that arise from Crohn’s disease.
- Immunomodulators reduce inflammation by suppressing the immune system but can take several weeks or longer to start working. A doctor may prescribe these if a person’s symptoms do not respond to other medications.
- Biologics are drugs that target and suppress the immune system. Doctors usually only prescribe these drugs if other treatments have not been effective.
A person may require surgery to treat complications of Crohn’s disease. Types of surgery may include:
- Small bowel resection. This is where a surgeon removes part of the small intestine and then reconnect the two ends.
- Large bowel resection. Also known as a subtotal colectomy, this is where a surgeon removes part of the large intestine and then reconnect the two ends.
- Proctocolectomy. In this surgery, a surgeon removes the entire colon and rectum. Afterward, a person will need to use an ostomy pouch to collect stools through a small opening in the abdomen.
Over-the-counter medications, such as pain relievers and vitamin supplements, can also help with symptoms. A person should take these in addition to prescription medication.
Diet is an important way to manage Crohn’s disease symptoms. A person is often less able to absorb nutrients from their food and drink. A healthful diet has a good balance of protein, vitamins, minerals, fats, and fiber. This can help a person to get the nutrients they need and maintain good energy levels.
Some people may find that certain foods or drinks trigger or worsen their symptoms. Common examples include spicy foods or dairy products. Keeping a food diary may help a person to identify possible triggers.
People with Crohn’s disease should seek medical advice before making major changes to their diet.