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Tuesday, 3 December 2013

Colitis - The Causes

 Colitis is defined as a condition of inflammation of the large intestine, including the colon, caecum and rectum.

A.1. Causes The causes of colitis as a result of types
A.1.1. Inflammatory bowel disease (IBD)(Ulcerative colitis and Crohn's disease)
1. Ulcerative colitis
The pathogenesis of inflammatory bowel disease (IBD) is multifactorial, with some patients presenting additional autoimmune symptoms.. In the study to describe these features, in order to differentiate a subgroup of colitis associated with autoimmunity (CAI) from CUC and  28 consecutive children with inflammatory colitis associated with primary sclerosing cholangitis (PSC), celiac disease, or AI hepatitis were compared with a matched control group of 27 children with isolated UC., by the Hôpital Necker-Enfants Malades, Service de Gastroentérologie pédiatrique, showed that in CAI the main digestive symptoms at disease onset were abdominal pain (12/28) and bloody strings in the stool (12/28), along with a high prevalence of autoimmune diseases in relatives, as compared with bloody diarrhea in the ulcerative colitis (CUC) group (26/27)(9a).

2. Crohn's disease
Crohn's disease and ulcerative colitis evolve with a relapsing and remitting course. In the study of included 63 ulcerative colitis (UC) and 41 Crohn's disease (CD) patients. Forty-seven healthy patients were included as the control group for the determination of the frequency and factors of prolonged QT dispersion that may lead to severe ventricular arrhythmias in patients with inflammatory bowel disease (IBD), indicated that  prolonged QTcd was found in 12.2% of UC patients, and in 14.5% of CD patients compared with the control group (P < 0.05). A significant difference was found between the insulin values (CD: 10.95 ± 6.10 vs 6.44 ± 3.28, P < 0.05; UC: 10.88 ± 7.19 vs 7.20 ± 4.54, P < 0.05) and HOMA (CD: 2.56 ± 1.43 vs 1.42 ± 0.75, P < 0.05; UC: 2.94 ± 1.88 vs 1.90 ± 1.09, P < 0.05) in UC and CD patients with and without prolonged QTcd(9b).

A.1.2. Microscopic colitis (Collagenous and lymphocytic colitis)
Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. According to the study by University of Sacred Heart, the epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management(10).
Other researchers indicated that Collagenous and lymphocytic colitis are well-described conditions causing chronic watery diarrhoea. A peak incidence from 60 to 70 years of age with a female predominance mainly in collagenous colitis is observed. Both conditions are characterised by a (near) normal colonoscopy, but with specific histologic findings on colonic biopsies. Histopathologically, both conditions are characterised by distinct epithelial abnormalities and a dense lymphoplasmocytic infiltrate. Distinct features consist of a characteristic collagen band deposition in the subepithelial layer in collagenous colitis and a markedly increased number of intra-epithelial lymphocytes in lymphocytic colitis(10a)
a. Collagenous colitis (CC)
Collagenous colitis (CC), a form of microscopic colitis, is characterized by a thick subepithelial collagen layer in the colon in the presence of chronic nonbloody watery diarrhoea and macroscopically normal-appearing colonic mucosa. According to the Hepatology and Nutrition, The Hospital for Sick Children, typically affecting elderly adults, CC is rare in children with only 12 cases previously reported in the literature, but we report a case of a 4-year-old girl with CC associated with eosinophilic gastritis(10b).

b. Lymphocytic colitis
In the study to evaluate the biopsy specimens from the terminal ileum of 32 patients with the histopathological diagnosis of lymphocytic colitis or collagenous colitis and 11 control individuals  for the presence or absence of ileal mucosal abnormalities and for the number of intraepithelial lymphocytes, assessed by immunohistochemical stains for the pan T-cell marker, CD3, showed that the mean CD3 counts in patients with lymphocytic/collagenous colitis were significantly higher than those in the control group. Seven of 14 patients with collagenous colitis and 14 of 18 patients with lymphocytic colitis revealed an increase in intraepithelial T lymphocytes when compared with the control group (P =.001). Other notable changes included ileal villous atrophy in one case of lymphocytic colitis and in three cases of collagenous colitis and epithelial damage with thickened subepithelial collagen in two cases of collagenous colitis(10c).

A.1.3. Iatrogenesis
May be as a result of chance, medical error, negligence, social control, unexamined instrument design, etc.
1. Diversion colitis
Diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients,  according to the study by Department of Medicine, Medical College of Wisconsin(10d)

2. Chemical colitis
Chemical colitis can occur as a result of accidental contamination of endoscopes or by intentional or accidental administration of enemas containing various chemicals. Most cases have occurred after accidental contamination of endoscopes with glutaraldehyde and/or hydrogen peroxide. There have been multiple case reports of chemical colitis resulting from unintentional administration of caustic chemicals. Intentional administration of corrosive enemas has been implicated in sexual practices, bowel cleansing, or in suicide attempts. Patients present with nonspecific symptoms including abdominal pain, rectal bleeding, and/or diarrhea, according to the study byStanford University School of Medicine, Stanford(10e).

A.1.4. Ischemic colitis
Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underestimated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable, according to the study by
Gastroenterology Unit Venizelion General Hospital of Heraklion(10f). Other study indicated that ischemic colitis is the most common manifestation of gastrointestinal ischemia. The presumed etiologies are numerous; however, it typically develops spontaneously. It is classified into the transient type, stricture type, and gangrenous type. The majority of patients with ischemic colitis, excluding the gangrenous type, follow a benign clinical course in the absence of major vasculature occlusion. It usually presents as an acute abdominal illness with bloody diarrhea(10g).

A.1.5. Infectious colitis (Clostridium difficile colitis)
In the study of diagnosis of Clostridium difficile colitis is increasing in frequency, with worsening patient outcomes of the data of one hundred fifty-seven patients diagnosed with C difficile colitis between 1994-2000., conducted by University of Washington, showed that the frequency of C difficile colitis remains high and seems to be associated with increasing mortality. Among patients with positive C difficile toxin assay results, immunocompromise and delayed diagnosis no longer seem to be associated with higher risk for death. All patients taking antibiotics are at risk and require early recognition and aggressive medical intervention(10h). Also according to the study by Baylor College of Medicine and Kelsey Research Foundation,  infectious colitis is diagnosed in someone with diarrhea and one or more of the following: fever and/or dysentery, stools containing inflammatory markers such as leukocytes, lactoferrin, or calprotectin, or positive stool culture for an invasive or inflammatory bacterial enteropathogen including Shigella, Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (STEC) or Clostridium difficile, or colonic inflammation by endoscopy(10i).

A.1.6. Indeterminate colitis and Atypical colitis
1. Indeterminate colitis(IC)
The term indeterminate colitis (IC) is an interim, or preliminary, descriptive term used by pathologists for cases of inflammatory bowel disease (IBD) in which a definite diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) cannot be established based on the information available at the time of surgical sign-out. Most cases are due to fulminant ulcerative colitis, a condition in which the classic pathologic features of UC are often obscured and may overlap with CD. For instance, fulminant UC may show early superficial fissuring ulceration, transmural lymphoid aggregates and relative rectal sparing, simulating CD. Other common causes for establishing a diagnosis of IC include confusion of backwash ileitis in UC for terminal ileal involvement in CD, failure to accept hard criteria, such as granulomas, or segmental disease, as representative of CD, and failure to recognize unusual variants of UC that can cause CD-like patchiness of disease(10k).
Approximately 4% to 5% of all patients with inflammatory bowel disease will be left with the diagnosis of IC. A diagnosis of indeterminate colitis (IC) is based on endoscopic, histologic, and radiologic findings when the criteria for either Crohn's colitis or ulcerative colitis (UC) cannot be definitively established. Population-based studies have demonstrated that the average annual incidence of IC ranges 1.6 to 2.4/100,000 versus 7.3 to 13.6/100,000 for UC. At the time of initial diagnosis of inflammatory bowel disease, up to 10% to 15% of patients will be diagnosed as having IC, according to the study by Brigham and Women's Hospital(10j).

2. Atypical colitis
Atypical colitis is a phrase used to define  a colitis that does not conform to criteria for accepted types of colitis. By considering the clinical history and symptoms, the pathologist should be able to reach the correct diagnosis in most cases. However, the spectrum of morphologic changes associated with watery diarrhea syndrome appears to be broader than originally thought. Morphologic changes more often associated with chronic inflammatory bowel disease or even chronic ischemic or infectious colitis have been noted in patients with clinically established microscopic colitis, according to the study by St. Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust(10l).

A.1.7. Fulminant colitis
Fulminant colitis is defined as any colitis that has become worse rapidly.
There is a report of a  33-yr-old white male presented with bloody diarrhea, leukocytosis, and left lower quadrant direct and rebound tenderness after a self-administered concentrated hydrofluoric acid enema while intoxicated from intranasal cocaine administration. Intraoperative flexible sigmoidoscopy and a gastrografin enema revealed severe mucosal ulceration and edema in the rectum and sigmoid colon. Laparotomy revealed an ulcerated, necrotic, and purulent sigmoid colon and intraperitoneal pus(10m).
Other in the review of the records of 4796 inpatients diagnosed as having C difficile colitis from January 1, 1996, to December 31, 2007, and identified 199 (4.1%) with fulminant C difficile colitis, as defined by the need for colectomy or admission to the intensive care unit for C difficile colitis, showed that the inhospital mortality rate for fulminant C difficile colitis was 34.7%. Independent predictors of mortality included the following: (1) age of 70 years or older, (2) severe leukocytosis or leukopenia (white blood cell count, >or=35 000/microL or <4000/microL) or bandemia (neutrophil bands, >or=10%), and (3) cardiorespiratory failure (intubation or vasopressors). When all 3 factors were present, the mortality rate was 57.1%; when all 3 were absent, the mortality rate was 0%. Patients who underwent colectomy had a trend toward decreased mortality rates (odds ratio, 0.49; 95% confidence interval, 0.21-1.1; P = .08). Among patients admitted primarily for fulminant C difficile colitis, care in the surgical department compared with the nonsurgical department resulted in a higher rate of operation (85.1% vs 11.2%; P < .001) and lower mortality rates (12.8% vs 39.3%; P = .001). Patients admitted directly to the surgical department had a shorter mean (SD) interval from admission to operation (0 vs 1.7 [2.8] days; P = .001)(10n).

A.2. Other causes
2. Sarcoidosis
Although clinically recognizable gastrointestinal (GI) system involvement with sarcoidosis is extremely rare, we report a case of a 51-year-old Caucasian male granulomatous as a result of Sarcoidosis. Enterocolitis Colonoscopy showed scattered right colon ulcerations and erythema. The terminal ileum appeared normal. Biopsies from the duodenum, terminal ileum, and colon showed intramucosal non-caseating granulomas with focal multinucleate giant cell formation in a background of chronic active duodenitis, ileitis, and colitis. Liver biopsy showed moderate non-specific chronic hepatitis with non-caseating granulomas present within portal and lobular parenchyma. The clinical presentations, along with biopsy results were suggestive of sarcoidosis(11).

3. Low level of both serum and tissue PON1
PON1 is known as an HDL-associated antioxidant enzyme that inhibits the oxidative modification of LDL and oxidative stress plays a role in the pathogenesis of mesenteric ischemia. According to the study to investigate the changes in PON1 activity and lipid profile in an experimental ischemic colitis model of 45male Wistar albino rats, showed that there was a significant decrease in both serum and tissue PON1 activity in ischemic colitis group (P < 0.01, for each). Similarly, arylesterase levels showed a parallel decrease in both tissue and serum of the experimental group (P < 0.01 and P < 0.001, retrospectively). MDA, an oxidative stress marker, was seen to increase in the experimental group (P < 0.01, tissue; P < 0.05, serum). In experimental group, there was a significant rise in serum total cholesterol and LDL levels (P < 0.001, for each). However, HDL level decreased significantly (P < 0.001). Triglycerides did not show any change between the groups (P > 0.05)(12).

4. Smoking, dehydration, NSAID (non-steroidal anti-inflammatory drugs) use, constipation and contraceptive use
Pathophysiology of ischemic colitis in young people is in most cases unknown. Possible contributing factors in our study were smoking, dehydration, NSAID (non-steroidal anti-inflammatory drugs) use, constipation and contraceptive use. (13a). But epidemiologic data suggest that smoking increases the risk and the severity of Crohn's disease (CD), although it may protect patients with ulcerative colitis (UC)(13), but others found no detrimental effects of smoking on the disease course of CD and no clear beneficial effects on the course of UC(14).

5. Anemia
Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. there is a report of a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel(15).

6.  Etc.

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