Crohn's Disease: Symptoms, Causes, Types, Complications, and Treatment

www.health.harvard.edu

Definition:

Is a chronic transmural inflammatory disease that can involve the whole GI-tract from the mouth to the perianal Area.

The transmural inflammatory nature of Crohn's disease often leads to fibrosis and to obstructive clinical presentations. The transmural inflammation can also result in sinus tracts that burrow through and penetrate the serosa, giving rise to microperforations and fistulae.

Areas of involvement in percent:

-          Small bowl, usually distal ileum 80%

-          Ileocolonic area 50%

-           Colon 20 %, with sparing the rectum in 50 % in Patients

-          Perianal area 30%

-          Mouth, stomach and duodenum 5-15%

Epidemiology:

In America 3.1 to 20.2 cases per 100,000 person-years

Age between 15 and 40 years with second peak between 50 and 80

Female are slightly more than male

Approximately 10 to 25 percent of individuals with IBD have a first degree relative with either Crohn's disease or ulcerative colitis 

Etiology: is unknown

Clinical manifestations:

Symptoms of the disease:

-          diarrhea, usually chronic without gross blood 

-          Abdominal pain: crampy pain, usually in lower right quadrant

-          Fatigue

-          Weight los

-          Fever

Symptoms of disease’s complications:

1-      Fistulas: are connection between two organs with epithelial line.  45% of patients develop fistulas before the diagnosis, the cumulative risk of developing a fistula in 10 years 33% and in 20 years is 50%:

There are many types of fistulas:

- enteroenteric fistula are usually symptomless and may present as palpable mass

- enterovesical fistula present with recurrent urinary tract infections, pneumaturia

- enterovaginal fistula: present with fecal or gas passage through the vagina

- enterocotaneus fistula: bowel content drains to the surface of the skin

- fistulas to the retroperitoneum: cause Posoasabscesses, ureter obstruction with            hydronephrosis.

2-      Abscesses cause abdominal pain, fever, palpable mass, and tenderness by localized peritonitis. Penetration with generalized peritonitis is rare but still can happen.

3-      Perianal disease: present in 30% in patients and include anal fissure, perianal abscess, and anorectal fistula.

4-      Constrictions and obstructions with abdominal pain, vomiting.

5-      Malabsorption:

Causes deficiency manifestation: vitamin B12 deficiency

Bile salts malabsorption in terminal ileum cause a compensatory high production in bile acid (ab 50-60 cm ileus resection), this compensation will not be enough by 100 cm ileus resection, und will lead to:

Watery diarrhea due to effect of bile acid on the colon

Fatty diarrhea due to fat malabsorption  

Gallen stones due to the reduction in bile acid to cholesterol ratio in the bladder which make the bile more lithogen

6-      Symptoms of other gastrointestinal involvement:

Aphthous in mouth, dysphagia in esophagus, Magen-out obstruction.

Extraintestinal symptoms:

-          Arthritis: in 20% in patients, usually large joints, central, such as sacroiliitis, ankylosing spondylitis

-          Eye: 5% in Patients: episcleritis, uveitis, iritis

-          Skin: 10 % in Patients: erythema nodosum, pyoderma gangrenosum

-          Primary sclerosing cholangitis: 5%.

-          Venous and arterial thromboembolism

-          Renal Stones

-          Osteoporosis due to steroid therapy and impaired Vit D and calcium absorption

-          Vit B12 Deficiency with pernicious anemia

DDx:

-          Infectious colitis

-          Lactulose intolerance: abdominal pain, diarrhea and flatulence after ingestion of milk or its products

-          Irritable bowel syndrome: abdominal pain with altered bowel habits

-          Ulcerative colitis:

Suggestive for CD are:

Involvement of the small bowel

Sparing of the rectum

Perianal disease

Absence of the gross bleeding

Focality of the lesions.

Fistula formations

Granulomas presence

-          Another DDx vary due to the location of the affected bowl segments:

Appendicitis, diverticulitis, ischemic colitis, carcinoma etc.…

Diagnosis:

1-      Suggesting clinic

2-      Labor: CBC: anemia with leukocytosis

CRP and ESR are elevated

B12, Iron deficiency

3-      Fecal protectin may help identify patients with intestinal inflammation and can be used to monitor patients for postoperative recurrence after ileocolic resection for Crohn's disease. Levels of >100 μg/g indicate endoscopic recurrence with a sensitivity in the range of 89%. In patients with an infliximab-induced remission, fecal calprotectin of >160 μg/g has a sensitivity of 91.7% and a specificity of 82.9% to predict relapse

4-      Endoscopy:

-          Coloscopy with ileum intubation:

Edema, skip lesions (focal ulcerations), cobblestone appearance (polypoid changes)

Histologic: inflammation with ulcerations (confirming but not diagnostic), granulomas in 30% (diagnostic but DDx for granulomas must be excluded)

-          Gastroscopy

-          Wireless capsule endoscopy

-          enteroscopy

5-      Imaging studies:

CT-enterography and MRT-enterography to evaluate the small bowel

Abdomen-CT by complications

MRT by perianal disease

Phenotypic classification.

The international standard of phenotypic classification is currently the 2005 Montreal revision of the Vienna classification. This classification system includes age of onset, disease location, and disease behavior.

-          A1 refers to disease onset at 16 years of age or younger, A2 disease onset between 17 and 40 years of age, and A3 over 40 years.

-          Disease location is divided into L1 (terminal ileum), L2 (colon), L3 (ileocolonic), and L4 (upper GI involvement).

-          Disease behavior is divided into B1 (nonstricturing, nonpenetrating), B2 (structuring), and B3 (penetrating). The letter “p” is appended to the B subtype if there is the presence of perianal fistulizing disease.

-          Location tends to remain stable and behavior tends to progress from B1 to B2 or B3 over the course of disease

Therapy:

General principles:

Clinical evidence of improvement should be taken within 2-4 weeks of Therapy, maximal improvement should happen in 12-16 Weeks.

Goal of the therapy to induce remission and maintain it

Therapy differs due to disease’s activity:

1- Mild to moderate Crohn disease:

Patient can eat and drink well, weight loss <10%, no complications such as fever, dehydration, abdominal mass, or obstruction:  CDAI 150-220:

-          5 ASA (aminosalicylates): sulfasalazine and mesalazine:

Sulfalazine 6-9 g/Day: in colonic/ileocolonic disease BUT NOT in small bowel CD

Mesalazine: its use has no prove of efficacy and shouldn’t be used in active CD

-          Antibiotics: ciprofloxacin and metronidazole;

its use has no prove of efficacy and shouldn’t be used in active CD

-          Glucocorticoids: prednisolone, budesonide

Budisonide 9 mg /day by ileocecal disease (less Corticosteroid Side effects)

2- Moderate to severe disease

Patient with sig. weight loss, failure to therapy of mild to moderate disease or complications such as fever, dehydration, abdominal mass, intermittent nausea or vomiting without obstruction. CDAI > 220-450

3- Refractory disease:

-          Repeatedly relapse after achieving remission with first-line agents

-          Remain symptomatic despite adequate doses of glucocorticoids (steroid-resistant), antibiotics

-          Flare when glucocorticoids are decreased or stopped (steroid-dependent)

To be treated like moderate to severe disease

-          Oral corticosteroids:

As short-term therapy to relive the symptoms

Prednisolon 40-60 mg/day over 1-2 weeks then reduce successive within no more 3 months

-          Immunomodulators:

A response to these medications will usually be seen within three to six months. During this period, patients often require concomitant steroid therapy with a gradual reduction in the steroid dose after one to two months of treatment with azathioprine or 6-MP.

Azatioprin 1.5-2.5 mg/Kg/day for maintenance of remission AND NOT as remission induction

6 Mercaptopurin: 0.75-1.5 mg/kg/day for maintenance of remission AND NOT as remission induction

TPMT (mercaptopurine methyltransferase) should be tested before initial use of Azatiopron/6 MP

SE: Bone marrow suppression, Malignancy

Methotrixat:

A response should be seen within three months. For patients on steroid therapy, the steroid should be continued during this period with a gradual lowering of the dose.

25 mg i.m . /Week: as remission maintenance, when response achieved, dosage of 15 to 12.5 mg/week s.c. , p.o. or i.m. could be enough.

SE: hepatotoxicity, bone marrow suppression

Concomitant therapy with folic acid 1 mg/day may diminish adverse effects to methotrexate

-          Anti TNF Agents: Infliximab i.v., adalimumab s.c. /2weeks, certolizumab s.c. / 4 weeks (not approved in Europe)):

By corticosteroid resistance/Thiopurine or MTX refractory

Assessment of latent or active infections should be initiated before beginning with therapy (Tuberculosis, Hepatitis B)

Vaccination status should IDEALY be reviewed and updated before initiated therapy,

for induction of remission and remission maintenance

Combination therapy of infliximab with immunomodulators (thiopurines) is more effective than treatment with either immunomodulators alone or infliximab alone

Infliximab: 5-10 mg/kg/ 8 Weeks.

4- Severe-fulminant disease persistent symptoms despite therapy with i.v. corticosteroid or biologic agents, obstruction, abscess, peritonitis signs, cachexia, CDAI > 450:

-          Intravenous corticosteroids should be used to treat severe or fulminant Crohn's disease 40-60 mg/day

-          Infliximab may be administered to treat fulminant Crohn's disease

MAINTENANCE THERAPY OF LUMINAL CROHN'S DISEASE

-          Once remission is induced with corticosteroids, a thiopurine 50 mg/day or methotrexate 25 to 12.5 mg/Week should be considered

-          Patients who are steroid dependent should be started on thiopurines or methotrexate with or without anti-TNF therapy

-          Oral 5-aminosalicylic acid is not recommended for long-term treatment

-          Corticosteroids are not effective for maintenance of medically induced remission in Crohn's disease and should not be used for long-term treatment

-          Anti-TNF therapy, specifically infliximab 5-10 mg/kg/ 8 Weeks, adalimumab, and certolizumab pegol, should be used to maintain remission of anti-TNF-induced remission, Combination with thiopurine or Methotrexate is more effective BUT at higher risk of malignancy and should be considered individually

-          There is no higher risk of opportunistic infections with the combination of thiopurines and anti-TNFs compared with either medication alone

POSTOPERATIVE CROHN'S DISEASE: MAINTENANCE, PREVENTION, AND TREATMENT

-          Postoperative recurrence of Crohn's disease can be defined by endoscopic findings or clinical symptoms

-          Patients at low risk for postoperative CD recurrence are: nonsmokers, do not have penetrating disease, and have never had a prior surgical resection.

No treatment after surgery in this population with subsequently performing a 6-month postoperative colonoscopy to assess for the presence of CD recurrence would be reasonable.

-          Patients who are nonsmokers, who have penetrating disease without a prior history of surgical resection, and who have received no prior medication should receive thiopurines with or without metronidazole (no more than 3 months), and subsequently undergo a colonoscopy at 6 months. If there is evidence of CD on the colonoscopy, then anti-TNF therapy should be added.

-          Patients who have had a prior resection within a 10-year period should receive (ab week 4 postoperative)  anti-TNF therapy with or without an immunomodulator and undergo a subsequent colonoscopy at 6 months postoperatively.

MEDICAL MANAGEMENT OF CROHN'S DISEASE COMPLICATIONS:

1.       Fistulae:

-          30% of Patients would have fistulae

-          infliximab 5 mg/kg administered at weeks 0, 2, and 6 and then every 8 weeks as maintenance therapy. Combination therapy with azathioprine has superior efficacy than monotherapy, but should NOT be done as long term therapy due to malignancy risk

Drainage of abscesses (surgically or percutaneously) should be undertaken before treatment of fistulizing Crohn's disease with anti-TNF agents

-          Antibiotics may be effective and should be considered in treating simple perianal fistulas

Metronidazol 400 mg x2 for 8 weeks/ Ciprofloxacin 500 mg x2 for 8 Weeks

-          Steroids and sulfasalazine have not been successful for inducing fistula closure

2.       Localized peritonitis:

-          bowel rest and broad-spectrum antibiotics i.v. for 7-10 days, followed be two- to four-week course of outpatient oral therapy with ciprofloxacin and metronidazole should be considered.

-          Intestinal resection should be considered in nonresponders.

-          If patient on corticosteroid, then a small increase in the dose may be required. for those not previously on steroids, withholding steroids to avoid masking any further sepsis is to be advised.

3.       Abscesses:

-          medical management with antibiotics

-          percutaneous drainage,

-          surgery with resection of involved intestinal segments.

4.       Small bowl obstruction:

-          Conservative therapy with intravenous hydration, nasogastric suction, and parenteral nutrition is often successful, with a response seen within 24 to 48 hours.

-          Parenteral glucocorticoids should be considered in nonresponders.

-          Surgery is reserved for those patients who do not respond to these noninvasive measures OR who have evidence of small bowel ischemia.

Written by: Ayman Zoaa

I’m a resident doctor living in Bremerhaven-Germany, my goal here is to explain medical stuff as easy and practical as possible. My second purpose is to help those who are trying to begin specializing in Germany.About my profession, I’m 30 years old, was born in Syria on 1989, I studied medicine at the University of Aleppo between 2007 and 2013, then I traveled to Germany and began my actual work before about 3 Years. I have got my medicine certificate recognized in Germany after I had made the recognition test and the medical language test.I’m specializing in internal medicine, and then I’ll proceed to gastroenterology, and hopefully endocrinology.I find writing interesting, and it also helps me to keep my information up to date, what we- medical people - need.Let us keep in touch through singing up, and through the contact-from, i will answer your Questions gladly