Coronavirus: Stem Cell therapy
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Crohn’s Disease
— 2015-08-18
Crohn’s disease(CD)
Inflammation of the intestine, especially the small intestine, with swelling, redness, and loss of normal bowel functions. Inflammation may be caused by the immune system attacking the body itself instead of foreign cells.
Although most patients present with Crohn’s disease(regional enteritis) in their 20s or 30s, the disease can present at any age. There is a second, smaller peak of incidence in 70-80-year-olds. The incidence of CD is rising. There is an increased risk of GI cancer with CD, especially with long-standing disease and Crohn colitis; screen long-term (>8 years) CD patients every other year for cancer.
CD tends to be more indolent than UC(Ulcerative colitis) and therefore also tends to be less responsive to treatment. It is harder to get these patients off steroids. Patients with CD are more likely to have perianal fistulae and abscesses. They are also more likely to have strictures, inflammatory masses, and associated obstruction. One big problem with CD is the high rate of recurrence. It was once thought to be 50% at 10 years, but this is the symptomatic recurrence rate. Radiologic/endoscopic recurrence rate is 75% at 3 years. Osteoporosis is common in patients with Crohn’s disease. About 70% have abnormal bone density-due to chronic disease, vitamin D deficiency, and/or steroids.
Although most patients present with Crohn’s disease(regional enteritis) in their 20s or 30s, the disease can present at any age. There is a second, smaller peak of incidence in 70-80-year-olds. The incidence of CD is rising. There is an increased risk of GI cancer with CD, especially with long-standing disease and Crohn colitis; screen long-term (>8 years) CD patients every other year for cancer.
CD tends to be more indolent than UC(Ulcerative colitis) and therefore also tends to be less responsive to treatment. It is harder to get these patients off steroids. Patients with CD are more likely to have perianal fistulae and abscesses. They are also more likely to have strictures, inflammatory masses, and associated obstruction. One big problem with CD is the high rate of recurrence. It was once thought to be 50% at 10 years, but this is the symptomatic recurrence rate. Radiologic/endoscopic recurrence rate is 75% at 3 years. Osteoporosis is common in patients with Crohn’s disease. About 70% have abnormal bone density-due to chronic disease, vitamin D deficiency, and/or steroids.
Diagnosis
CD is diagnosed by finding patchy, focal, and aphthous ulcers and deep transmural ulcers with occasional strictures and fistula formation. Granulomas, infrequently found on biopsy specimen of these ulcers, are pathognomonic. A tetrad to remember for “Crohn colitis”:
1) Rectal sparing
2) Skip lesions
3) Perianal disease
4) Ileocecal involvement
1) Rectal sparing
2) Skip lesions
3) Perianal disease
4) Ileocecal involvement
Hallmark sign and symptoms
• Fever
• Right lower quadrant pain
• Diarrhea (non-bloody)
• Abdominal mass
• Weight loss (unintentional)
• Fatigue
• Bloating after meals (postprandial)
• Abdominal cramping due to spasm
• Borborygmi (loud, frequent bowel sounds)
• Fistula formation (bowel-bowel, bowel-stomach, bowel-bladder, bowel-skin, bowel-vagina)
• Aphthous ulcers (oral ulcerations)
• Nephrolithiasis
• Right lower quadrant pain
• Diarrhea (non-bloody)
• Abdominal mass
• Weight loss (unintentional)
• Fatigue
• Bloating after meals (postprandial)
• Abdominal cramping due to spasm
• Borborygmi (loud, frequent bowel sounds)
• Fistula formation (bowel-bowel, bowel-stomach, bowel-bladder, bowel-skin, bowel-vagina)
• Aphthous ulcers (oral ulcerations)
• Nephrolithiasis
Symptom
Patients with CD may present with fever, abdominal pain, and systemic symptoms.
One classic but uncommon feature is the string sign, which may be seen in the terminal ileum during a small bowel follow-through.
The terminal ileum is so edematous and/or fibrotic that the lumen is compressed and can be visualized only as
a “string” of contrast. If you see this narrowing of the lumen elsewhere in the colon, with or without CD, it
is called an apple-core lesion, which suggests cancer. Bowel involvement in CD: 30% colon only, 30% small bowel only, and 30-50% both.
Initially, a definitive diagnosis cannot be established in up to 15% of patients with IBD. Serologic tests (p-ANCA and ASCA, anti-saccharomyces antibody) can be useful in indeterminant cases. p-ANCA is associated with UC(Gastrointestinal Cancer) and ASCA(Anti-Saccaromyces Cerevisiae antibodies) with CD. Panels containing additional serologic markers, which increase sensitivity/specificity, are commercially available.
One classic but uncommon feature is the string sign, which may be seen in the terminal ileum during a small bowel follow-through.
The terminal ileum is so edematous and/or fibrotic that the lumen is compressed and can be visualized only as
a “string” of contrast. If you see this narrowing of the lumen elsewhere in the colon, with or without CD, it
is called an apple-core lesion, which suggests cancer. Bowel involvement in CD: 30% colon only, 30% small bowel only, and 30-50% both.
Initially, a definitive diagnosis cannot be established in up to 15% of patients with IBD. Serologic tests (p-ANCA and ASCA, anti-saccharomyces antibody) can be useful in indeterminant cases. p-ANCA is associated with UC(Gastrointestinal Cancer) and ASCA(Anti-Saccaromyces Cerevisiae antibodies) with CD. Panels containing additional serologic markers, which increase sensitivity/specificity, are commercially available.
Terminal Ileum Problems in CD
Problems related to disease/resection of the terminal ileum are found in CD-but ordinarily not in UC.
• Calcium oxalate kidney stones
• Steatorrhea
• Gallstones
• B12 deficiency
• Hypocalcemia (from vitamin D malabsorption)
• Bile acid-induced diarrhea
• Nutrient malabsorption
• Calcium oxalate kidney stones
• Steatorrhea
• Gallstones
• B12 deficiency
• Hypocalcemia (from vitamin D malabsorption)
• Bile acid-induced diarrhea
• Nutrient malabsorption
Treatment for Chohn’s Disease
Medical treatment of CD includes many of the same drugs as that for UC.
• 5-aminosalicylate (5-ASA, mesalamine-slow release formulations)
• Olsalazine
• Corticosteroids (prednisone, budesonide)
• Infliximab, adalimumab, and certolizumab pegol
• Metronidazole
• Ciprofloxacin
• Azathioprine (and its metabolite, 6-mercaptopurine)
• 5-aminosalicylate (5-ASA, mesalamine-slow release formulations)
• Olsalazine
• Corticosteroids (prednisone, budesonide)
• Infliximab, adalimumab, and certolizumab pegol
• Metronidazole
• Ciprofloxacin
• Azathioprine (and its metabolite, 6-mercaptopurine)
Surgery and Recurrence
Surgery is only for intractable disease and specific serious complications. Previously, 60% of Crohn’s patients required surgery in the first 5 years and then again after 8 years. These numbers are decreasing with improved medical therapy options(especially 6-MP, infliximab).
The incidence of recurrence after surgery depends on:
• Site-ileocolic is highest.
• Nature of the complication-obstruction, perforation, and abscesses have a higher rate of recurrence.
Essentially, the worse the disease is where you cut, the more likely is the recurrence at that site. Colectomy and ileostomy provide the best results for Crohn colitis when there is no Heal inflammation (> 60% have no recurrence).
The incidence of recurrence after surgery depends on:
• Site-ileocolic is highest.
• Nature of the complication-obstruction, perforation, and abscesses have a higher rate of recurrence.
Essentially, the worse the disease is where you cut, the more likely is the recurrence at that site. Colectomy and ileostomy provide the best results for Crohn colitis when there is no Heal inflammation (> 60% have no recurrence).
Stem Cell Therapy for CD
Many researchers have studied stem cell therapies for CD patients. CD stem cell medicine development has not completed yet, which are on clinical trial now.
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