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Crohn’s disease
- 1. BY: DIANA TABANSI JAN 30TH 2018
- 2. INTRODUCTION Crohn’s Disease is an idiopathic, chronic, transmural inflammatory process of the bowel that can affect any part of the gastro intestinal tract from the mouth to the anus. Individuals with this condition often experience periods of symptomatic relapse and remission.
- 3. Most cases involve the terminal ileum, colon or both 30% small bowel (usually terminal ileum), 40% ileum/colon, 25% colon, 5% stomach/duodenum/esophagus
- 4. EPIDEMIOLOGY Higher number of cases of Crohn’s disease found in western industrialized nations. Its prevalence with the highest incidence being reported in northern Europe, the United Kingdom and North America The overall incidence of Crohn disease in Europe is about 5.6 per 100,000 inhabitants (7.0 per 100,000 person-years in northern centers vs 3.9 in southern centers). Crohn disease is reported to be more common in white patients than in black patients and rare in Asian and Hispanic children.
- 5. Incidence figures in Asia range from 0.5 to 4.2 cases per 100,000 persons. The lowest recorded rates of new cases appear to be in South Africa (0.3- 2.6 cases per 100,000 persons) and Latin America (0-0.03 cases per 100,000 persons). The age of onset of Crohn disease has a bimodal distribution. The first peak occurs between the ages of 15 and 30 years (late adolescence and early adulthood), and the second occurs mainly in women between the ages of 60 and 70 years. The rate of Crohn disease is 1.1-1.8 times higher in women than in men.
- 6. IBD PATIENTS IN JAMAICA All IBD patients seen at the University Hospital of the West Indies, Jamaica, between January 2000 and January 2010 were reviewed. There were 103 patients, 64 had ulcerative colitis (UC) and 39 Crohn's disease (CD), ratio of 1.6:1. In patients with UC there were 21 males and 42 females (M:F=0.5:1), whilst in those with CD 21 were males and 17 females (M:F=1.2:1). The mean age was 32.3 (range 2-84) years. Only 3.9% of patients were current smokers, 6.8% were past smokers. A family history of IBD was present in 7%. In CD patients, 56% had colitis only and 21% had small bowel disease. In UC patients, 31% had pancolitis, and 44% left-sided disease.
- 7. The duration of disease was 5 years in 32%, 5-20 years in 54%, and more than 20 years in 14%. The main presenting features were diarrhea (93%), rectal bleeding (56%), abdominal pain (48%), weight loss (25%) and nausea and vomiting (19%). For patients with CD, presentation also included fistulas and small bowel obstruction. Extraintestinal manifestations were present in 38% of patients, and joint pain was present in 67.5% of them. Other extraintestinal manifestations were primary sclerosing cholangitis in 20% and pyoderma gangrenosum in 15%. In conclusion ,IBD is relatively uncommon in Jamaica. UC is more common than CD. Most cases of CD had colitis only.
- 8. Anatomy of the digestive tract
- 11. ETIOLOGY The exact cause of Crohn disease remains unknown. Genetic, microbial, immunologic, environmental, dietary, vascular, and psychosocial factors have been implicated, as have smoking and the use of oral contraceptives and nonsteroidal anti- inflammatory agents (NSAIDs). Interaction between the predisposing genetic factors, environmental factors, host factors, and triggering event is likely necessary for the disease to develop.
- 12. GENETIC CAUSE Mutations in the NOD2 /CARD15 gene are associated with Crohn's disease. NOD2 : nucleotide-binding oligomerization domain containing 2 CARD15 :Cathapse Activation Recruitment Domain Over 30 genes that show genetics play a role in the disease, either directly through causation or indirectly as with a mediator variable.
- 13. Another early genome-wide association study (GWAS) looked at Jewish and non-Jewish case-control cohorts and identified 2 SNPs in the IL23R gene, which encodes 1 subunit of the IL-23 receptor protein. However, another study found that the Arg381Gln substitution is associated with childhood onset of IBD in Scotland.
- 14. 21 new loci were found that were associated with an increased risk of developing Crohn disease. Among the new loci were some very interesting implications, including the genes CCR6, IL12B, STAT3, JAK2, LRRK2, CDKAL1, and PTPN22. Most of these genes are involved in signal transduction in certain immune function, as well as genes involved more directly with immune function.
- 15. The interlectin gene (ITLN1) is expressed in the small bowel and colon and is involved in recognition of certain microorganisms in the intestine. ATG16L1 gene, which encodes the autophagy-related 16- like protein involved in the autophagosome pathway that processes intracellular bacteria.
- 16. IMMUNOLOGIC Interleukins and TNF-α have also been implicated in the disease process. Crohn disease is characterized by a Th1 cellular immune response pattern that leads to production of IL-12, TNF-α, and interferon gamma Increased production of TNF-α by macrophages in patients with Crohn disease results in increased concentrations of TNF- α in the stool, blood, and mucosa
- 17. MICROBIAL Infectious agents such as Mycobacterium paratuberculosis, Pseudomonas species, and Listeria species have all been implicated in the pathogenesis of Crohn disease, suggesting that the inflammation seen with the disease is the result of a dysfunctional, but appropriate, response to an infectious source.
- 18. ENVIRONMENTAL Environmental influences such as tobacco use seem to have an effect on Crohn disease. Smoking has been shown to double the risk of Crohn disease, whereas the risk of developing ulcerative colitis is lower in people who smoke than in those who have never smoked or in those who stopped smoking before their diagnosis It has been suggested that a diet high in fatty foods may increase the risk of Crohn disease.
- 19. PATHOPHYSIOLOGY
- 20. Microscopically: The initial lesion starts as a focal inflammatory infiltrate around the crypts. ulceration of superficial mucosa. inflammatory cells invade the deep mucosal layers noncaseating granulomas . Neutrophil infiltration into the crypts forms crypt abscesses, Chronic damage may be seen in the form of villous blunting in the small intestine as well.. Although granuloma formation is pathognomonic of Crohn disease, its absence does not exclude the diagnosis.
- 22. MACROSCOPICALLY Hyperemia and edema of the involved mucosa. discrete superficial ulcers form over lymphoid aggregates cobblestone appearance Transmural inflammation As Crohn disease progresses, it is complicated by obstruction or deep ulceration leading to fistulization by way of the sinus tracts penetrating the serosa, microperforation, abscess formation, adhesions, and malabsorption
- 24. CLASSIFICATION
- 25. Crohn disease activity indices These scoring systems are used principally for assessing the efficacy of treatment and evaluating new therapies for research purposes. The Crohn Disease Activity Index (CDAI), which was developed for use in adults Pediatric Crohn Disease Activity Index (PCDAI)
- 29. TYPES OF CROHN’S DISEASE Ileocolitis Ileitis Gastroduodenal Crohn's disease Jejunoileitis Crohn's (granulomatous) colitis
- 30. PRESENTATION The characteristic presentation in Crohn disease is abdominal pain and diarrhea, which may be complicated by intestinal fistulization or obstruction. Unpredictable flares and remissions characterize the long- term course
- 31. SIGNS AND SYMPTOMS Prolonged bloody or Non bloody diarrhea Weight loss, anorexia Nausea, vomiting Generalized fatigability Fever(usually low grade) RLQ pain and/or mass Perianal/perirectal disease with abscess, fistulas, structuring Bloating Constipation and obstipation Extraintestinal manifestations
- 35. Primary sclerosing cholangitis: is a progressive chronic liver condition of unknown etiology that increases the risk for cholangiocarcinoma and colorectal cancer in patients with IBD. Patients can be asymptomatic with mild elevations of transaminase and alkaline phosphatase, or they may present with advanced findings of cholangitis and jaundice Primary sclerosing cholangitis has an established strong association with IBD, particularly ulcerative colitis.
- 36. COMPLICATIONS
- 37. PHYSICAL EXAMINATION Vital signs: Normal, but possible presence of tachycardia in anemic or dehydrated patients; possible chronic intermittent fever Gastrointestinal: May vary from normal to those of an acute abdomen; assess for rectal sphincter tone, gross rectal mucosal abnormalities, presence of hematochezia Genitourinary: May include presence of skin tags, fistulae, ulcers, abscesses, and scarring in the perianal region; nephrolithiasis, hydronephrosis, and enterovesical fistulae Musculoskeletal: Possible arthritis and arthralgia, particularly of the large joints
- 38. Dermatologic: May show pallor or jaundice, mucocutaneous or aphthous ulcers, erythema nodosum, and pyoderma gangrenosum Ophthalmologic: May reveal episcleritis; possible uveitis Growth delay: Decreased growth velocity (eg, height), pubertal delay
- 39. Perianal disease
- 40. DIAGNOSITIC WORK UP Routine laboratory studies include the following: CBC count Chemistry panel Liver function tests Inflammatory markers Stool studies Serologic tests :. Antibodies to the yeast Saccharomyces cerevisiae (ie, anti-S cerevisiae antibodies [ASCA])
- 41. IMAGING STUDIES Imaging modalities used for Crohn disease include the following: Plain abdominal radiography Barium contrast studies (eg, small bowel follow-through, barium enema, enteroclysis) CT scanning of the abdomen CT enterography or magnetic resonance enterography: Replacing small bowel follow-through studies MRI of the pelvis Abdominal and/or endoscopic ultrasonography Nuclear imaging (eg, technetium-99m hexamethyl propylene amine oxime, indium- 111) Fluorine-18-2-fluoro-2-deoxy-D-glucose scanning combined with positron emission tomography or CT scanning
- 42. PROCEDURES The following procedures may help in the evaluation of Crohn disease: Endoscopic visualization and biopsy (eg, upper gastrointestinal endoscopy, esophagogastroduodenoscopy, endoscopic retrograde cholangiopancreatography) Colonoscopy, ileocolonoscopy Small bowel enteroscopy Interventional radiology: For percutaneous drainages of abscesses
- 43. Crohn disease. Aphthous ulcers. Double- contrast barium enema examination in Crohn colitis demonstrates numerous aphthous ulcers. Barium contrast studies (eg, small bowel follow-through, barium enema, enteroclysis Cobblestoning. Spot view of the terminal ileum from a small-bowel follow-through study demonstrates linear longitudinal and transverse ulcerations that create a cobblestone appearance.
- 44. Crohn disease. Crohn colitis. Double- contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon. several narrowing and stricturing, consistent with the string sign. Crohn disease. Single-contrast barium enema study demonstrates stricturing of the caput cecum, the so-called coned cecum.
- 45. Computed Tomography Scanning Crohn disease. Mesenteric inflammation. CT scan demonstrates inflammatory mass in the right lower quadrant associated with thickening of the wall and narrowing of the lumen of the terminal ileum Crohn disease. Fibrofatty proliferation. CT scan in a patient with Crohn colitis in the chronic phase demonstrates wall thickening of the right colon, an absence of adjacent mesenteric inflammatory stranding, and a large amount of fatty proliferation around the right colon separating the colon from the remainder of the gut, so-called creeping fat.
- 46. Magnetic Resonance Imaging Balanced FFE image shows marked bowel wall thickening and luminal narrowing of the terminal ileum. Measurement on the balanced FFE sequence can be less accurate due to the black border artifact (arrows) PERIANAL FISTULA
- 47. ULTRASONOGRAPHY Sonogram of a thickened bowel wall demonstrates the so-called pseudokidney appearance. Crohn disease of the terminal ileum with CT and sonographic correlation. Note hypoechoic wall thickening, loss of the gut signature, and the hyperechoic line representing the narrowed lumen.
- 48. ENDOSCOPY AND COLONOSCOPY This procedure is useful in obtaining biopsy tissue, which helps in the differentiation of other diseases, in the evaluation of mass lesions, and in the performance of cancer surveillance. Ileocolonoscopy has a sensitivity of 74% and a specificity of 100% in the assessment of Crohn disease, leading to a positive predictive value of 100% as a diagnostic test. For patients with Crohn disease of the colon, magnifying endoscopy allows a more detailed view of the mucosal surface than conventional endoscopy does
- 50. Endoscopic features in a patient with Crohn's disease. (a) Erythema and loss of vascular pattern in a patient with Crohn's disease. (b) A few aphthous ulcers in the colon in a patient with Crohn's disease. (c) Discrete ulcers in the colon in a patient with Crohn's disease. (d) Multiple deep longitudinal ulcers in colon in a patient with Crohn's disease. (e) Longitudinal ulcers with cobblestone appearance in the colon. (f) Cobblestone appearance in a patient with Crohn's disease
- 51. Differential diagnosis Amebiasis Ulcerative Colitis Appendicitis Bacterial Gastroenteritis Behcet Disease Celiac Disease and HLA-DQ2/DQ8 Diverticulitis Giardiasis Intestinal Carcinoid Tumor Intestinal Tuberculosis Irritable Bowel Syndrome Ischemia Tuberculosis Viral Gastroenteritis
- 52. MANAGEMENT Pharmacotherapy: 5-Aminosalicylic acid derivative agents (eg, mesalamine rectal, mesalamine, sulfasalazine, balsalazide) Corticosteroids (eg, prednisone, methylprednisolone, budesonide, hydrocortisone, prednisolone) Immunosuppressive agents (eg,azathioprine, mercaptopurine, methotrexate, tacrolimus) Monoclonal antibodies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab) Antibiotics (eg, metronidazole, ciprofloxacin) Antidiarrheal agents (eg, loperamide, diphenoxylate-atropine) Bile acid sequestrants (eg, cholestyramine, colestipol) Anticholinergic agents (eg, dicyclomine, hyoscyamine, propantheline)
- 53. SURGERY Unlike ulcerative colitis, Crohn disease has no surgical cure. Most patients with Crohn disease require surgical intervention during their lifetime. Surgical management of the terminal ileum, ileocolon, and/or upper gastrointestinal tract may include the following : Resection of the affected bowel Ileocolostomy or proximal loop ileostomy Drainage of any septic foci with later definitive resection Strictureplasty Bypass Endoscopic dilatation of symptomatic, accessible strictures
- 54. Surgical management of the colon may include the following : Subtotal or total colectomy with end ileostomy (laparoscopic or open approach) Segmental or total colectomy with or without primary anastomosis Total proctocolectomy or proctectomy with stoma creation
- 55. Complications of surgery The most common complication of surgical treatment of Crohn disease is the development of intraperitoneal adhesions. Patients with Crohn disease undergoing abdominal surgery are also at increased risk for the development of enterocutaneous fistulae as a result of their surgery. Those who are being treated with steroids or immunosuppressive agents may be at increased risk of wound or intra-abdominal infections.
- 56. PROGNOSIS Appropriate medical and surgical therapy helps patients to have a reasonable quality of life, with an overall good prognosis and an extremely low risk of a fatal outcome. In the first year after diagnosis, the relapse rate approaches 50%, with 10% of patients having a chronic relapsing course. Most patients develop complications that require surgery, and postoperative clinical relapse occurs in a significant proportion. Patients with proximal small bowel disease have a higher risk of mortality than those who have ileal or ileocecal disease. The excess mortality may be ascribed to complications of Crohn disease
- 59. REFERENCES https://www.gponline.com/crohns-disease-clinical- review/gi-inflammatory-bowel-disease/crohns- disease/article/1213250 http://www.crohnscolitisfoundation.org/what-are-crohns- and-colitis/what-is-crohns-disease/types-of-crohns- disease.html https://emedicine.medscape.com/article/172940-clinical https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959440/ https://www.belmarrahealth.com/crohns-disease-vs- ulcerative-colitis-differences-in-symptoms-causes-and- treatment/
Notas do Editor
- . A greater proportion of colonic and distal Crohn disease has been diagnosed in older patients, whereas younger patients have predominantly ileal disease. In general, the frequency of IBD is similar in males and females, with some studies showing a very slight female predominance. This pattern is reversed with pediatric IBD, which has a higher incidence in boys than in girls (pediatric male-to-female ratio, ~1.6:1).
- When the genetics of Crohn disease were first investigated, a strong association was found with chromosome 16 (IBD1 gene), which led to the identification of 3 single nucleotide polymorphisms (SNPs), 2 missense and 1 frameshift, in the NOD2 gene (now called CARD15), the first gene clearly identified as a susceptibility gene for Crohn disease. ATTENTION:NOD2/CARD15 is a polymorphic gene involved in the innate immune system. Of its more than 60 variations, 3 play a role in 27% of patients with Crohn disease, primarily in those with ileal disease.
- interestingly, this study also described the promising nature of certain therapies that block the function of IL-23. Further research suggested that one particular polymorphism in the IL23R gene showed the strongest association in a German population.
- ATG16L1 gene, which encodes the autophagy-related 16-like protein involved in the autophagosome pathway that processes intracellular bacteria. [
- TNF-α has been shown to play a critical role in the inflammation in this disease.
- Concerns about the measles vaccine and the development of the disease have proved to be unfounded. Although appendectomy has been suggested to be protective in ulcerative colitis, it is not a protective factor in Crohn disease.
- Pathogens activates the immune system by APC . TH 1 releases cytokines interferon gama, TNF alpha which further stimulate immune response. The cytokines attract inflammatory cells like macrophages which start releasing even more inflammatory substances like proteases, platelet activating factor and free radicals, which contributes to inflammation. So for some unknown cause one of this steps is unregulated and out of control inflammatory response, so all this inflammatory substance are floating around the G.I tissue which will lead to destruction of the healthy tissue. This dysfunctional immune response is thought to be a product of genetics. In a study from 2012, investigators suggested that genetic predispositions for inflammatory bowel disease (IBD) lead to abnormal epithelial barrier integrity and homeostasis, deficits in autophagy, deficiencies in innate pattern recognition receptors, and problems with lymphocyte differentiation, especially in Crohn disease
- Microscopically, the initial lesion starts as a focal inflammatory infiltrate around the crypts, followed by ulceration of superficial mucosa. Later, inflammatory cells invade the deep mucosal layers and, in that process, begin to organize into noncaseating granulomas (see the image below). The granulomas extend through all layers of the intestinal wall and into the mesentery and the regional lymph nodes. Neutrophil infiltration into the crypts forms crypt abscesses, leading to destruction of the crypt and atrophy of the colon. Chronic damage may be seen in the form of villous blunting in the small intestine as well. Ulcerations are common and are often seen on a background of normal mucosa. Although granuloma formation is pathognomonic of Crohn disease, its absence does not exclude the diagnosis.
- GRANULOMA AND BLUNTING OF VILLI
- the initial abnormality consists of hyperemia and edema of the involved mucosa. Later, discrete superficial ulcers form over lymphoid aggregates and are seen as red spots or mucosal depressions (see the image below). These can become deep, serpiginous ulcers located transversely and longitudinally over an inflamed mucosa, giving the mucosa a cobblestone appearance. The lesions are often segmental, being separated by healthy areas, and are referred to as skip lesions. [11] Transmural inflammation results in thickening of the bowel wall and narrowing of the lumen. As Crohn disease progresses, it is complicated by obstruction or deep ulceration leading to fistulization by way of the sinus tracts penetrating the serosa, microperforation, abscess formation, adhesions, and malabsorption. [1] Bowel obstruction is caused initially by significant edema of the mucosa and associated spasm of the bowel. Obstruction is intermittent and can often be reversed by means of conservative measures and anti-inflammatory agents. With further disease progression, the obstruction becomes chronic because of fibrotic scarring, luminal narrowing, and stricture formation. [1] Fistulae may be enteroenteral, enterovesical, enterovaginal, or enterocutaneous. The inflammation extending through the bowel wall may also involve the mesentery and surrounding lymph nodes. Creeping fat may be seen when the mesentery wraps around the bowel surface . [1] Serosal inflammation causes adhesions; thus, free perforations are less common in Crohn disease than in other inflammatory bowel conditions. [1]
- Montreal classification, which classifies CD according to its predominant phenotypic elements L4 – Isolated upper GI disease; L4 is a modifier that can be added to L1-L3 when there is concomitant upper GI involvement B1 – Nonstricturing, nonpenetrating; B1p: nonstricturing, nonpenetrating with perianal involvement B2 – Stricturing; B2p: stricturing with perianal involvement B3 – Penetrating; B3p: penetrating with perianal involvement Crohn disease activity indices Multiple scoring systems incorporating the patient’s history, physical examination findings, and laboratory data have been developed to assess disease activity in adults with Crohn disease. These scoring systems are used principally for assessing the efficacy of treatment and evaluating new therapies for research purposes. One such index is the Crohn Disease Activity Index (CDAI), which was developed for use in adults. The Pediatric Crohn Disease Activity Index (PCDAI) was developed and validated in 1990; the results are correlated with the physician’s global assessment and with the Harvey-Bradshaw index (HBI), and they have significant interobserver reliability. The important difference between the PCDAI and the CDAI is the inclusion of growth parameters in the PCDAI score. A modified PCDAI (Mod PCDAI), consisting of the laboratory measures of the PCDAI plus the C-reactive protein (CRP) level, has been shown to correlate with the PCDAI, the physician’s assessment, and fecal calprotectin. [54] This modified index can be used as an alternative to the PCDAI, with the advantage of having additional objective laboratory values embedded in it. [54] Other authors have described a short PCDAI. [55] Other activity indices and their parameters used for clinical and research purposes include the following: HBI – General well-being, abdominal pain, number of liquid stools per day, presence of abdominal masses, and complications or EIMs Seo index – General well-being, amount of blood in stool, number of bowel movements during the day and the night, urgency of defecation, and number of extracolonic manifestations Perianal Crohn Disease Index (PDAI) – Perianal discharge, pain with restriction of daily activities, restriction of sexual activity, physician scoring of the type and number of perianal disease, and presence of induration Fistula Drainage Assessment – Fistula healing, ranging from heavy drainage or abscess to complet
- Crohn disease activity indices Multiple scoring systems incorporating the patient’s history, physical examination findings, and laboratory data have been developed to assess disease activity in adults with Crohn disease. These scoring systems are used principally for assessing the efficacy of treatment and evaluating new therapies for research purposes. One such index is the Crohn Disease Activity Index (CDAI), which was developed for use in adults. The Pediatric Crohn Disease Activity Index (PCDAI) was developed and validated in 1990; the results are correlated with the physician’s global assessment and with the Harvey-Bradshaw index (HBI), and they have significant interobserver reliability. The important difference between the PCDAI and the CDAI is the inclusion of growth parameters in the PCDAI score. A modified PCDAI (Mod PCDAI), consisting of the laboratory measures of the PCDAI plus the C-reactive protein (CRP) level, has been shown to correlate with the PCDAI, the physician’s assessment, and fecal calprotectin. [54] This modified index can be used as an alternative to the PCDAI, with the advantage of having additional objective laboratory values embedded in it. [54] Other authors have described a short PCDAI. [55] Other activity indices and their parameters used for clinical and research purposes include the following: HBI – General well-being, abdominal pain, number of liquid stools per day, presence of abdominal masses, and complications or EIMs Seo index – General well-being, amount of blood in stool, number of bowel movements during the day and the night, urgency of defecation, and number of extracolonic manifestations Perianal Crohn Disease Index (PDAI) – Perianal discharge, pain with restriction of daily activities, restriction of sexual activity, physician scoring of the type and number of perianal disease, and presence of induration Fistula Drainage Assessment – Fistula healing, ranging from heavy drainage or abscess to complet
- Ileocolitis The most common form of Crohn's, ileocolitis affects the end of the small intestine (the ileum) and the large intestine (the colon). Symptoms include diarrhea and cramping or pain in the right lower part or middle of the abdomen. This type is often accompanied by significant weight loss. Ileitis This type affects only the ileum. Symptoms are the same as ileocolitis. In severe cases, complications may include fistulas or inflammatory abscess in right lower quadrant of abdomen. Gastroduodenal Crohn's disease This type affects the stomach and the beginning of the small intestine(the duodenum). Symptoms include loss of appetite, weight loss, nausea, and vomiting. Jejunoileitis This type is characterized by patchy areas of inflammation in the upper half of the small intestine (the jejunum). Symptoms include mild to intense abdominal pain and cramps following meals, as well as diarrhea. In severe cases or after prolonged periods, fistulas may form. Crohn's (granulomatous) colitis This type affects the colon only. Symptoms include diarrhea, rectal bleeding, and disease around the anus (abscess, fistulas, ulcers). Skin lesions and joint pains are more common in this form of Crohn's than in others
- Diarrhea is usually not grossly bloody and is often intermittent. If the colon is involved, patients may report diffuse abdominal pain accompanied by mucus, blood, and pus in the stool Crampy or steady right lower quadrant or periumbilical pain may develop; the pain precedes and may be partially relieved by defecation Those with perianal disease may have debilitating perirectal pain, malodorous discharge from the fistula, and disfiguring scars from active disease or previous surgery Enterovesical fistulae may manifest as recurrent urinary tract infections and pneumaturia, enterovaginal fistulae as feculent vaginal discharge, and enterocutaneous fistulae as feculent soiling of the skin. Development of fistulae into the mesentery or luminal microperforation may result in intra-abdominal or retroperitoneal abscess formation. Patients may also present with complaints suggestive of intestinal obstruction. Initially, the obstruction is secondary to inflammatory edema and spasm of the bowel and manifests as postprandial bloating, cramping pains (lower right quadrant), and borborygmi. Once the bowel lumen becomes chronically narrowed from fibrosis, patients may complain of constipation and obstipation.
- The differential diagnosis of this condition is vast and includes IBD-associated arthritides such as arthralgia (5-20%), ankylosing spondylitis (1-26%), psoriatic arthritis, reactive arthritis, and sacroiliitis, as well as fibromyalgia and osteoporosis and osteoporosis-related fractures. In adults, the arthritis occurs when the disease is active and can affect large and small joints. Type 1 peripheral arthritis is pauciarticular (< 5 joints), and is strongly associated with IBD activity and other EIMs. The joint most commonly involved is the knee. Type 2 peripheral arthritis is polyarticular and independent of disease activity. The metacarpophalangeal (MCP) joint is the most commonly involved site; less frequently, the knees, ankles, shoulders, proximal interphalangeal (PIP) joint, and metatarsophalangeal (MTP) joint may be involved. Sweet syndrome :skin disease characterized by the sudden onset of fever, an elevated white blood cell count, and tender, red, well-demarcated papules and plaques that show dense infiltrates by neutrophil granulocytes on histologic examination. Orofacial granulomatosis Angular and aphthous stomatitis Acrodermatitis enteropathica Alopecia Metastatic Crohn disease Crohn disease of the vulva and penis Psoriasis
- Erythema nodosum:The lesions of erythema nodosum are raised, red, tender nodules that appear primarily on the anterior surfaces of the lower leg. These ulcers can be either solitary or multiple and either unilateral or bilateral, and they can range in size from several centimeters to distribution along an entire limb. Additional extraintestinal diseases Bone metabolic disorders include osteopenia and osteoporosis. Hematologic manifestations include iron deficiency anemia, vitamin B-12 deficiency anemia, folate deficiency anemia, anemia of chronic disease, autoimmune hemolytic anemia, thrombocytosis, anemia due to GI bleeding, and thrombosis. Genitourinary manifestations include nephrolithiasis, obstructive uropathy, glomerulonephritis, and amyloidosis. Pulmonary manifestations include granulomatous lung disease, fibrosing alveolitis, and pulmonary vasculitis. Cardiovascular manifestations include pericarditis, myocarditis, and vasculitis.
- About 5-10% of patients with primary sclerosing cholangitis have Crohn disease, but only 2% of Crohn disease patients develop primary sclerosing cholangitis. There is a 2:1 male prevalence for the disorder.
- The major cause for complication is due to the flare ups and remission of the disease. During remission the inflammed tissues are healed and this will cause the formation of scarred tissue which can lead to a stricture and obstruuction Colonic malignancy is a clinically significant complication of Crohn disease with colonic involvement. Chronic inflammation is the conjectured etiology for the development of dysplasia followed by cancer. Most cases of colorectal cancer develop from early histologic lesions referred to as low-grade dysplasia (LGD) or dysplasia-associated lesion or mass (DALM). Sporadic adenomas can also progress to colon cancer. These are premalignant or precancerous lesions that progress to cancer via a pathway of inflammation and genetic mutations.
- inspection of the perianal region can reveal skin tags, fistulae, ulcers, abscesses, and scarring. A rectal examination can help to determine sphincter tone and aid in detecting gross abnormalities of the rectal mucosa or the presence of hematochezia. In addition to local complications, various EIMs may be associated with Crohn disease, usually involving the skin, joints, mouth, eyes, liver, or bile ducts. [45] The most common EIMs are arthritis and arthralgia. The large joints (eg, hips, knees, ankles) are typically involved. [6] Examination of the skin and oral mucosa may show mucocutaneous or aphthous ulcers, erythema nodosum, and pyoderma gangrenosum. Skin examination may also reveal pallor in patients with anemia or jaundice in those with concomitant liver disease with cholestasis. Eye examination may reveal episcleritis. For the diagnosis of uveitis, a slit-lamp examination by an experienced physician is necessary.
- Anal fissures, peerianal abscess, fistula
- Crohn disease is initially diagnosed on the basis of a combination of clinical, laboratory, histologic, and radiologic findings. Laboratory study results are generally nonspecific but may be helpful in supporting the diagnosis and managing the disease. Serologic studies are sometimes used to facilitate differentiation of Crohn disease from ulcerative colitis or inflammatory bowel disease (IBD) of undetermined type. Complete blood cell count A complete blood count (CBC) is useful in detecting anemia, which may be due to multiple causes, including chronic inflammation, iron malabsorption, chronic blood loss, and malabsorption of vitamin B-12 or folate. Leukocytosis may be due to chronic inflammation, abscess, or steroid treatment. Chemistry panel Electrolyte analysis can help determine the patient’s level of hydration and renal function. Hypoalbuminemia is a common laboratory finding in patients with suboptimally treated Crohn disease. Additional common abnormalities include deficiencies in iron and micronutrients (eg, folic acid, vitamin B-12, serum iron, total iron binding capacity, calcium, and magnesium). Liver function test results may be elevated, either transiently (because of inflammation) or chronically (because of sclerosing cholangitis). Inflammatory markers Acute inflammatory markers, such as C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR), may correlate with disease activity in some patients. If Crohn disease activity is suspected, however, a normal ESR or CRP level should not deter further evaluation. Stool studies Stool samples should be tested for the presence of white blood cells (WBCs), occult blood, routine pathogens, ova, parasites, and Clostridium difficile toxin. These studies should also be used to rule out infectious etiologies during relapses and before the initiation of immunosuppressive agents. [6] Fecal calprotectin has been proposed as a noninvasive surrogate marker of intestinal inflammation in IBD. [62] The level of the inflammatory marker calprotectin in feces correlates significantly with endoscopic colonic inflammation in both ulcerative colitis and Crohn disease, and fecal lactoferrin is significantly correlated with histologic inflammation. [63] However, colorectal neoplasia and GI infection also increase fecal calprotectin; therefore, this study should be used with caution. At present, fecal calprotectin is not in widespread use, except in research protocols. In the future, this marker may be made more available to clinicians for following patients’ disease activity. There are 2 serologic tests that are currently used in efforts to differentiate ulcerative colitis from Crohn disease. Antibodies to the yeast Saccharomyces cerevisiae (ie, anti-S cerevisiae antibodies [ASCA]) are found more commonly in Crohn disease than in ulcerative colitis, whereas perinuclear antineutrophil cytoplasmic antibody (p-ANCA), a myeloperoxidase antigen, is found more commonly in ulcerative colitis than in Crohn disease. Additional serologic markers, such as Escherichia coli anti-ompC (outer membrane porin C), can be found in more than 50% of Crohn disease cases and in only a small percentage of ulcerative colitis cases. Pseudomonas fluorescens (anti-12) may be found in more than 50% of Crohn disease cases and in only 10% of ulcerative colitis cases. Flagellinlike antigen (anti-Cbir1) is associated independently with small bowel, intestinal penetrating, and fibrostenosing disease. These tests further increase sensitivity and diagnostic value.
- Plain Abdominal Radiography Abdominal radiography is a nonspecific test for evaluation of IBD; however, it can useful if there is concern about obstruction or perforation. If abdominal radiographs are obtained, findings may include mural thickening and dilatation, small bowel and colonic mucosal abnormalities, and abnormal fecal distribution with areas of colonic involvement without fecal material. Nuclear imaging:Leukocytes labeled with either technetium-99m-HMPAO (hexamethylpropylamine oxime) or indium-111 can be used to assess for active bowel inflammation in inflammatory bowel disease.
- Barium enema is noninvasive and usually well tolerated for evaluating features such as pseudodiverticula, fistulization, and the severity and length of colonic strictures Mucosal fissures, bowel fistulae, strictures, and obstructions can be visualized. However, barium studies are contraindicated in patients with known perforation, and water-soluble agents should be used in place of barium. Barium can also cause peritonitis.
- Computed tomography (CT) scanning is helpful in—and considered the imaging technique of choice for—the assessment of extramural complications as well as hepatobiliary and renal complications in adults and children. [ It may show bowel wall thickening, bowel obstruction, mesenteric edema, abscesses, or fistulae
- Magnetic resonance imaging (MRI) has been shown to yield a higher sensitivity and specificity than ileocolonoscopy (the criterion standard) both for diagnosing Crohn disease and for determining its severity It is especially useful for evaluating pelvic and perianal disease when one is investigating for evidence of perianal fistulae and abscesses
- Ultrasonography is a quick, inexpensive, and noninvasive screening method used for the diagnosis of IBD or for repeated evaluation for complications. [65, 66, 67] Abdominal ultrasonography can rule out gallbladder and kidney stones as well as detect enlarged lymph nodes and abscesses. However, it has a steep learning curve that yields a range of sensitivity that is operator-dependent. Because of their lack of radiation exposure, ultrasonography and MRI are often preferred to CT, especially in younger patients. Rectal endoscopic ultrasonography has been used as an alternative to MRI in the assessment of perianal disease.
- Colonoscopy also enables dilation of fibrotic strictures in patients with long-standing disease and has been used in the assessment of mucosal healing. In addition, it may be used in the postoperative period to evaluate surgical anastomoses as a means of predicting the likelihood of clinical relapse as well as the response to postoperative therapy. Endoscopy:In combination with chromoendoscopy (methylene blue), it is possible to analyze the surface staining pattern further to help identify neoplastic changes in situ and take targeted biopsies
- Anti-inflamatory Products such as mesalamine, which release 5-ASA in the distal small bowel when triggered by pH changes, are more useful in patients with small bowel Crohn disease. Controlled release of mesalamine is thought to begin at the pylorus and to continue at a constant rate throughout the small bowel and colon; consequently, this drug is sometimes used when proximal intestinal and gastric Crohn disease is found. steriodsA short course of corticosteroid therapy is indicated in patients with severe systemic symptoms (eg, fever, nausea, or weight loss) and in those whose condition does not respond to anti-inflammatory agents. Prednisone is generally helpful in acute inflammation without signs of obvious infection. Adding antibiotics such as ciprofloxacin or metronidazole is always beneficial if coexisting infection exists. Steroids are not indicated for maintenance, because of serious complications (eg, aseptic necrosis of the hip, osteoporosis, cataract, diabetes, and hypertension). Accordingly, once remission is achieved, the agent is slowly tapered. It should be noted that steroids do not modify disease or induce sustained mucosal healing. immunosuppresantIf steroid withdrawal proves difficult, immunosuppressants such as azathioprine or its active metabolite 6-MP may be considered. Treatment response is usually observed within 3-6 months. Because of the risk of bone marrow suppression, careful supervision is needed. Azathioprine (Azasan, Imuran) and mercaptopurine (Purinethol, Purixan). These are the most widely used immunosuppressants for treatment of inflammatory bowel disease. Taking them requires that you follow up closely with your doctor and have your blood checked regularly to look for side effects, such as a lowered resistance to infection and inflammation of the liver. They may also cause nausea and vomiting. Infliximab is a chimeric mouse-human monoclonal antibody against TNF-α that has shown promise in Crohn disease treatment; it blocks TNF-α in the serum and at the cell surface, leading to the lysis of TNF-producing macrophages and T cells. According to the American Gastroenterological Association (AGA), infliximab is indicated for the following: Treatment of patients with Crohn disease who do not achieve adequate clinical response despite treatment with conventional therapy (ie, a corticosteroid or an immunosuppressive agent) Treatment of fistulizing Crohn disease that is refractory to conventional therapy (ie, antibiotics, surgical drainage with examination under anesthesia, immunosuppressive therapy, or combinations thereof) Ustekinumab Ustekinumab inhibits interleukin (IL)-12 and IL-23 cytokines, which play a key role in inflammatory and immune responses. Diarrhea:Chronic diarrhea in Crohn disease responds well to antidiarrheal agents such as loperamide, bile acid binders (for bile acid diarrhea), diphenoxylate with atropine, and tincture of opium. Such agents should be considered with care in active colitis because of the risk of toxic megacolon. Anticholinergic:Abdominal cramps may be reduced with anticholinergic agents such as propantheline, dicyclomine, or hyoscyamine. These drugs should not be used if there is the possibility of a bowel obstruction.
- Proctocolectomy surgery to remove the colon and rectum is called a proctocolectomy.
- The risk of surgery at 5-year intervals after diagnosis is as follows [41] : 5 years after diagnosis – The cumulative probability of having only 1 surgical procedure is 37%; 2 or more surgical procedures, 12%; and no surgical procedures, 51% 10 years after diagnosis – The cumulative probability of having only 1 surgical procedure is 39%; 2 or more surgical procedures, 23%; and no surgical procedures, 39% 15 years after diagnosis – The cumulative probability of having only 1 surgical procedure is 34%; 2 or more surgical procedures, 36%; and no surgical procedures, 30%