INFLAMMATORY BOWEL DISEASE (IBD)/CROHN’S DISEASE/ ULCERATIVE COLITIS
The inflammatory bowel diseases (Crohn’s disese and ulcerative colitis) are chronic disorders with an intermittent nature for disease flares and remissions. Patients often present with abdominal pain, diarrhea, hematochezia (bloody stool), or mucoid stools. Other associated symptoms and diseases include aphthous ulcerations, seronegative arthritis, erythema nodosum, pyoderma gangrenosum, uveitis, iritis, anemia, perianal fistulas or fissures, oxalate nephrolithiasis, digital clubbing, and an increased risk for colorectal or small intestinal cancer and primary sclerosing cholangitis. Therapy should be directed at treating acute flares of disease and then adjusting to prolong the periods of disease remission. Factors which can aggravate underlying disease and induce flares include dietary stressors, NSAIDs, infections, and menstruation. Patients with IBD may also suffer from concomitant irritable bowel syndrome and may derive benefit from appropriate therapy.
ULCERATIVE COLITIS (UC)
Ulcerative colitis affects the mucosa of the large bowel usually in the left hemicolon and in most cases beginning with the rectum. Generally, the lesion is continuous from beginning to end without areas of normal mucosa. In some cases, disease is severe enough to affect the entire colon (pancolitis) and may even extend to the terminal ileum (backwash ileitis). The etiology is currently unknown, although several theories exist. Histologic changes of the colonic mucosa include congestion, ulcerations, an inflammatory infiltrate, and crypt abscesses. The disease is not transmural, being localized to the mucosa only. Patients generally present complaining of chronic, small volume diarrhea with hematochezia, abdominal pain and/or cramping, and rectal tenesmus (urgency to defecate). Severe disease may present with toxic megacolon and requires hospitalization. If megacolon is associated with perforation, emergency surgery is required.
Diagnosis is best established by direct visualization of the colonic mucosa via endoscopy. In patients with chronic diarrhea, the finding of fecal leukocytes without any identifiable bacterial pathogens is suggestive of UC although other etiologies could be responsible. An elevated ESR is often noted but is nonspecific. The finding of serum p-ANCA is associated with underlying UC as is the HLA-DR2 antigen.
Therapy is applied for both acute disease and to prolong the symptom free interval between disease flares. Acute disease that is mild to moderate may be treated with an oral aminosalicylates (sulfasalazine, olsalazine, mesalamine, or balsalazide), oral steroids (prednisone 40 to 60 mg/day) or infliximab (5 mg/kg at 0,2, and 6 weeks). 6-Mercaptopurine or azathioprine may be added when patients do not respond to steroid therapy as long as the patient can tolerate oral therapy. When using mesalamine compounds, oral sulfasalazine (4-6 grams/day) is often employed initially but may be poorly tolerated. If sulfasalzine cannot be tolerated, a trial of one of the other mesalamine compounds with either olsalazine, mesalamine (4.8-12 grams/day) or balsalazide (750 mg three tablets PO TID) should be initiated as all are equally effective. Rectal mesalamine or steroids are also effective in treating acute disease limited to the left hemicolon, and may be used to maintain remission for disease of the distal colon. Topical mesalamine for the treatment of mild to moderate distal disease (suppositories of 500 mg BID to TID or enemas of 1 to 4 gm QHS) or topical steroids(Cort enemas or budesonide enemas) may also be used to maintain remission.
In severe disease, intravenous corticosteroids in dosages equivalent to 40-60 mg of methylprednisolone or 300-400 mg of hydrocortisone per day are employed. Budesonide is one of the newer steroids employed for UC secondary to its decreased side effect profile. Once the patient improves clinically, they may be switched to an oral dose of prednisone (40-60 mg/day) followed by tapering of 5-10 mg/week until 20 mg/day which is then followed by tapering at 2.5-5 mg/week. Patients requiring long term use of steroids should be considered for osteoporosis prophylactic therapy. Antibiotics can be used during acute attacks with underlying infection, when acute disease is secondary to underlying Clostridium difficile infection, or if pouchitis develops after surgical intervention. If after five days of aggressive therapy the patient is still symptomatic, then adding a continuous infusion with cyclosporin A (target daily blood levels of 250-350 ng/mL) or performing a colectomy are viable treatment options. When patients respond to intravenous cyclosporin A, they may be converted to an oral dose of approximately 3 times the daily intravenous dosage. Tapering of the cyclosporin A may occur after the patients oral steroid has been tapered to a dose equivalent to 10 mg/day of prednisone.
Therapy to prolong remission includes 5-ASA compounds (sulfasalazine, mesalamine, and olsalazine) aminoslicylates, cyclosporin A, parenteral methotrexate, azathioprine, or 6-mercaptopurine although these agents are also used in acute disease. Steroids are not effective for preserving remission. Surgery may be curative in UC but is generally reserved for those patients with severe, refractory disease or patients who demonstrate dysplastic changes on surveillance biopsies. Postoperative complications include the development of pouchitis, which usually responds to medical management especially with antibiotics (metronidazole or ciprofloxacin)
Patients with severe disease who present with toxic megacolon should be treated aggressively in conjunction with surgical consultation. Toxic megacolon may be diagnosed by plain abdominal radiography demonstrating a transverse colon diameter greater than 5 cm. Patients should be given nothing orally. Supportive therapy includes aggressive fluid and electrolyte management plus nasogastric and rectal decompression. Patients may also require blood transfusions, fresh frozen plasma (if clotting abnormalities are noted), and intravenous albumin. Half of these patients will respond to medical management with intravenous steroids. If patients do not respond quickly, broad spectrum antibiotics should be started and intravenous cyclosporine A may be employed. If megacolon does not respond within 48 hours, surgery may be required.
In patients with long standing disease of greater than eight years duration, cancer surveillance with colonoscopy plus multiple biopsies every six to 12 months is recommended. High grade dysplasia is an indication for colectomy.
Crohn’s disease is an enteric inflammatory condition that is transmural and may involve any portion of the gastrointestinal (GI) tract from mouth to anus but generally the small intestine. Because it can affect the GI tract in so many varied locations, it may present with many differing symptoms. Most patients initially present during adolescence or early adulthood. Patients often present with GI complaints such as cramping, pain, large volume diarrhea, fistulas, perianal abscess, obstruction, and mucoid stools, often accompanied by systemic complaints to include fever, weight loss, anorexia, arthritis, erythema nodosum, malabsorption syndromes (B12, folate, iron), gallstones, osteopenia/osteoporosis, and delayed growth/development. There is an increased risk of malignancy in affected portions and surgically bypassed segments of the bowel. Sclerosing cholangitis should be suspected in patients with evidence of associated cholestatic liver disease.
A tender mass in the right lower abdominal quadrant is often noted on physical examination in patients with active disease. Since Crohn’s disease may affect any portion of the GI tract from mouth to anus, diagnostic techniques differ according to which portion of the GI tract is affected. Endoscopy allows direct visualization if the affected bowel can be reached via this manner. Enteroclysis or abdominal CT may prove useful for evaluating disease in those portions of the GI tract that are inaccessible to endoscopic evaluation. Nonspecific tests include positive fecal leukocytes and an elevated ESR. Positive serum assays for antibodies to Saccharomyces cerevisiae (ASCA) are associated with the diagnosis of Crohn’s disease (high specificity but low sensitivity). The antigens HLA-DR1 and HLA-DQw5 are also associated with Crohn’s disease.
Therapy is similar as for UC (see above); however, unlike UC, surgery is not curative in Crohn’s disease. Steroids are effective for inducing remission during disease flares; however, they are ineffective at maintaining periods of remission. Sulfasalazine is effective in the treatment of disease of the colon; whereas, the other aminosalicylates are more effective in maintaining remission with disease of the small intestine. When disease proves refractory to first line agents (aminosalicylates, antibiotics, and corticosteroids), a trial of azathioprine or 6-mercaptopurine should be considered versus a trial of infliximab. Surgery is useful for symptoms refractory to medical therapies, when patients can not continue therapy secondary to drug side effects, or when certain symptoms (obstruction, fistulas, abscess, hemorrhage, perforation,etc) develop. One complication encountered after extensive ileal resection is cholorrheic enteropathy (watery diarrhea that results secondary to bile salt malabsorption), which may respond to treatment with either cholestyramine or colestipol. Another difference in the therapy for Crohn’s disease is that antibiotics (metronidazole, ciprofloxacin, tetracyclines, or clarithromycin) may be a more effective therapeutic modality when compared to UC. Therapy with metronidazole should be continued for four to six months when treating perineal disease. Infliximab is a monoclonal antibody against tumor necrosis factor alpha that is an effective therapy for Crohn’s disease but not for UC.