Primary non-specific intestinal inflammations

·         Crohn‘s disease (ileitis terminalis, morbus Crohn) – chronic non-specific inflammation (up to granulomatous) affecting the entire thickness of the intestinal wall, inflammatory changes are segmental or plurisegmental, can affect any part of the digestive tube, most often the terminal ileum

·         Ulcerous colitis (proctocolitis idiopathica) – haemorrhagic-purulent to ulcerative inflammation of the mucosa and submucosa of the rectum and adjacent part of the colon (or the whole colon - proctocolitis, never affects the small intestine)

Etiopathogenesis is not known, the essential characteristics of IBD are considered to be:

Crohn disease – T_H lymfocyties produce a little of IL-4

Ulcerous colitis – reduced production of leukotrienes

Patological anatomy – comparison Crohn's disease and colitis ulcerosa

-          in Crohn's disease, the entire intestinal wall is affected (macroscopic thickening of the intestinal wall and mesentery), lymph nodes are enlarged, the involvement is segmental or plurisegmental - the affected sections alternate with unaffected ones (mucosa is hypertrophic and edematous, the image of cobblestones - elongated aphthous ulcers over lymphoid follicles surrounding the unaffected mucosa, serosal involvement leads to adhesions in which fistulas are formed, further progression with fibroproduction leads to stenosis, microscopically mucosal edema with polymorphonuclear infiltration, subsequent fibroproduction with formation of tuberculoid granulomas (epitheloid cells and Langhans  giant cells, unlike tbc, do not caseify) in submucosa, subserosa and regional nodules

-          in ulcerative colitis, only the mucosa and submucosa are affected (macroscopically we see contraction of the affected section) - the involvement is continuous, unlike in m. Crohn's - mucosa is hypertrophic and edematous with numerous ulcers with rolled edges, microscopically crypt abscesses (dilated crypts filled with polymorphonuclei, their disintegration leads to mucosal detachment and ulceration), serosa is shiny, mesocolon is not thickened

clinical course – comparison Crohn's disease and colitis ulcerosa

-          the course of m.Crohn is rather continuous (chronic), or acute imitating acute appendicitis, carcinogenesis is possible

-          the course of ulcerative colitis is rather sudden (or chronically exacerbating), manifested by rectal or colitis syndrome, carcinogenesis more pronounced than in m. Crohn

-          m. Crohn and ulcerative colitis are associated with extra-intestinal symptoms (immune diseases):

·         primary sclerosing cholangiitis, cholelithiasis, chronic pancreatitis

·         arthritis, ankylosing spondylitis

·         erythema nodosum, pyoderma gangrenosum, urticaria

·         uveitis, episcleritis, iritis, amyloidosis and others

localisation of GIT involvement

-          in Crohn's disease most often terminal ileum, then colon, small intestine, anorectal area, rarely other localisations (isolated involvement of oesophagus, stomach, duodenum, appendix)

-          in ulcerative colitis, the rectum is always affected, possibly with the adjacent colon (left-sided form) or the whole colon is affected (pancolitis)

complications

1.)   Crohn´s disease

-          abscesses (interstitial, pelvic, retroperitoneal, hepatic)

-          internal fistulas (enteroenteric, enterocolic, enterovesical, rectovaginal) and external (perineal, abdominal wall)

-          intestinal stenosis – ileus

-          perforation of the intestine– peritonitis

-          massive bleeding

-          toxic megacolon

-          malignant transformation (carcinoma)

2.)   colitis ulcerosa

-          massive bleeding

-          toxic megacolon

-          perforation of the intestine – peritonitis

-          anorectal affection (fissures, stricturas)

-          malignant transformation (carcinoma)

clinical manifestations and diagnosis of Crohn's disease

-          abdominal pain, diarrhea, weight loss, fat malabsorption, subfebrile, other symptoms depend on localization:

·         ileocoecal – pain in the right-lower abdomen, sometimes a palpable infiltrate mimicking appendicitis

·         small intestine - no diarrhea, but gas, belching and gagging 1-2 h after eating, stenosis - up to subileus

·         colon - mild enterorrhagia (unlike ulcerative colitis, where blood in stool is the rule)

·         anorectal - fissures, stenoses, fistulas

extraintestinal manifestations:

-   segmental colon involvement in the elderly, the whole colon is affected in the young, the rectum may or may not be affected

-   laboratory in active stage ↑ FW, ↑ CRP, signs of malnutrition, hypalbuminemia, ASCA (antibodies against brewer's yeast)

imaging techniques:

-          endoskopy (coloscopy with biopsy, enteroscopy)

-          X-ray (intestinal passage, enteroclysis, fistulography) – shows ulcers, stenosis

-          US, CT – assessment of intestinal wall thickness, abscesses, infiltration around the intestine

-          99Tc-leu scintigraphy - extent, activity, local complications, ev. Screening

clinical manifestations and diagnosis of colitis ulcerosa

-          according to the localization of two basic syndromes:

1.)   rectal syndrom – tenesmus (urge to pass stool with defecation of small amounts of stool or mucus with blood)

2.)   colitic syndrom – crampy abdominal pain with watery diarrhea with admixture of blood and mucus, loss of albumin

-          general symptoms include anorexia, weakness, anaemia, weight loss and extraintestinal manifestations

-          pANCA, cANCA (perinuclear and cytoplasmic neutrophil antibodies)

-          stool examination – appearance (mucus+blood), culture (differentiation from infectious colitis)

imaging techniques:

-          endoskopy (rectoscopy, coloscopy)

-          X-ray (irrigography - not in acute condition, can cause megacolon)

-          US, CT (low outcomes), NMRi (abscesses)

-          scintigraphy ¹¹¹In-leu

conzervativ treatment of primary non-specific intestinal inflammations

1)  aminosalicylates (sulfasalazine, mesalazine, olsalazine)

2)  corticoids

3) imunosupresives (azathioprin and mercaptourin, cyclosporin A, metotrexat, infliximab – blocator of TNF-α receptor)

4) ATB (metronidazol, ciprofloxacin)

5) dietary restrictions (most often high protein low residual diet, temporary PEN)

surgical treatment of m.Crohn

-          conservative treatment is only symptomatic, delays surgery but does not prevent it (on the contrary, long-term administration of corticosteroids worsens healing - 50% of patients need surgery within 10 years, half of them have an ileostomy) - the response to surgery is small, however, recurrences occur more often the later the surgery was performed

-          surgical treatment is indicated when conservative treatment fails and for complications (urgent - massive bleeding, intestinal obstruction, toxic megacolon, perforation peritonitis, abscess, elective - intestinal stenoses, fistulas, infiltrates, dysplasia and carcinoma):

·         resection with anastomosis or stomia

·         stricturoplasty and balloon dilatation of stenoses

·         drainage of abscesses

·         fistulotomia

-          resections should be as short as possible (possibility of repeated resections in case of recurrences, necessity to preserve at least 60 cm of the small intestine, stricturoplasty rather than resection is preferred), end-to-end anastomosis, stoma in acute conditions or if the rectal area cannot be reconstructed, no pouch creation during reconstruction in the rectal area:

·         segmental resection of the small and large intestine

·         ileocecal resection with ileo-acendentoanastomosis

·         right-sided hemicolectomy with ileo-transversoanastomosis

·         subtotal colectomy with ileo-rectoanastomosis

·         proctocolectomy with ileostomy

·         abdominoperineal amputation with colostomy

-          if the rectum is not affected, it is preferable to keep it even with a permanent ileostomy (saving the pelvic nerve plexus - sexual function, the disadvantage is the need for repeated checks of the rectum for inflammatory lesions)

surgical treatment of colitis ulcerosa

-          as contrasted with Crohn's disease, resection in ulcerative colitis provides a definitive solution to the problem

-          urgent in case of perforation, bleeding, endotoxemic shock and toxic megacolon - subtotal colectomy with ileostomy and blind closure of the rectum sec. Hartmann or its removal as a mucosal fistula in the lower pole of the surgical wound according to Mikulicz

-          elective in case of failure of conservative treatment, dysplasia or carcinoma, stricture or extracolonic manifestations, total proctocolectomy with ileostomy or with ileo-anal anastomosis using a pouch (J, S or W) is recommended

Non-specific intestinal inflammations (secondary)

a)      ischemic colitis

-          diseases caused by ischemia of a section of the large intestine (based on atherosclerosis, abdominal aortic aneurysm, embolism, vasculitis, after surgery and angiography, when the inferior mesenteric artery is injured), presents as:

1)   acute complete ischemia – infarction of the colon, leading to gangrene and manifesting as acute abdomen

2)   transient subacute ischemia – affects the mucosa and submucosa, does not lead to gangrene of the entire wall, manifests itself as haemorrhagic colitis with diarrhoea with blood, tenesmus and abdominal pain (diff. dg. ulcerative colitis), usually resolves or turns into

3)   chronic stadium – ischemic strikture – fibosis of the bowel wall and segmental strikture (dif. dg. Crohn, tumor)

-          the subacute and chronic form is located in the area of the ileal flexure (Griffith's critical point - in the case of imperfect collateral circulation between the a. mesenterica sup. et inf.), other authors question the existence of this point and place the maximum incidence of ischaemic colitis in the area of the colon ascendens

-          in the acute stage it is necessary to resect the gangrenous wall (often with colostomy and closure of the rectum sec. Hartmann), it is also necessary to resect the stenosis in the chronic stage, the subacute stage is treated conservatively - diet, vasodilators, ATB, analgesics

b)     postradiation colitis

-          it is an inflammatory damage to the colon due to radiation. A special subtype is radiation proctitis, which is an inflammation of the rectal mucosa

·      acute radiation proctitis, resp.colitis

-          Early changes are caused by the effect of radiation on rapidly dividing tissues in or near the irradiated area. As a result of radiation proctitis and colitis predominate increased stool counts, eventually mild diarrhea and tenesmus. Possible but rare complications include profuse diarrhea or rectal bleeding. The frequency of such more serious complications is around 1-3% depending on the technique used.

-          Endoscopy may show non-specific changes (oedema, loss of vascularity), but in 50% of patients the findings are normal. Histologically, focal involvement of the intestinal mucosa with edema of the lamina propria is characteristic, with "thinning" of the crypts. Intestinal epithelia lose their cylindrical shape and show regressive changes. In particular, condensation and disintegration of nuclear chromatin are characteristic. Small superficial erosions or deeper ulcerations appear in the mucosa. In the submucosa there is marked oedema and significant dilatation of the vascular structures, which are engorged.

·       chronic radiation proctitis, resp.colitis

-          the rate of chronic side effects is dose-dependent, but also related to the rate of radiation response and, in some rare cases, determined by the genotype of the individual (there are individuals with reduced tolerance to radiotherapy due to insufficiency of enzymes and proteins that repair DNA damage caused by the treatment). These side effects occur gradually and are very difficult to control

-          chronic mucosal involvement occurs most often within 24 months after the end of treatment, with most patients experiencing improvement or even resolution of symptoms within 2 years. In severe involvement, symptoms may persist for life. Grade 2 toxicity is 90 % responsive to treatment, grade 3 toxicity about 75 %

-          the damage is caused by involvement of the vascular plexus in the intestinal wall, where progressive obliterative endarteritis occurs. This results in tissue ischemia with fibroproductive changes and mucosal ulceration. Specific findings include neovascularization and hyalinization of connective tissue predominantly in the submucosa and under the serosa, with atypical fibroblasts and telangiectasias. Vascular changes with endothelial pooling, accumulation of foamy cells in the subendothelial region and atrophy and interstitial fibrosis of the muscularis propria are evident

-          endoscopically, we find focal redness and swelling, single to multiple confluent telangiectasias, which may bleed small spontaneously or contact. We see wiped submucosal vascular pattern, small superficial ulcerations, scars, rarely ulcers are deep or flat larger than 1cm2, strictures, fistulas. Typically, there is completely normal mucosa above the affected segment of the intestine

Treatment

-          in the acute phase, the problems are usually manageable with diet and regime measures or medication. We suppress intestinal motility, flatulence. Analgesics, spasmolytics are suitable for painful tenesmus. Antibiotics are usually not necessary for radiotherapy-induced diarrhoea. Probiotics are recommended for severe dysmicrobia

-          mucoprotective agents that stimulate cellular regeneration of the intestinal epithelium and increase mucus production and stimulate mucosal macrophages- e.g. sucralfate- may show a good effect

-          in the treatment of ulcerations of radiation proctitis we use suppositories or enemas with mesalazine, in severe cases corticosteroids in suppositories or topical corticosteroids in enemas. We treat telangiectasias with argon plasmacoagulation. Balloon dilatation is used for strictures. Painful fissures and fistulas or periproctal abscesses are indications for surgical management

c)      postantibiotic colitis

-          it is an acute inflammatory bowel disease associated with antibiotic administration. It includes a variety of manifestations ranging from transient mild diarrhoea to severe colitis with inflammatory mucosal plaques ('pablans' - 'pseudomembranes'). The severe form of inflammation is called pseudomembranous colitis.

Causes, risk factors

-          various antibiotics can alter the balance of the normal bacterial population (flora) in the colon, allowing certain abnormal bacterial strains to overgrow. The most common bacterium is the rod-shaped Clostridium difficile. This microbe produces two poisonous substances (toxins) capable of damaging the colonic mucosa

-          the most commonly involved antibiotics are clindamycin, ampicillin and so-called cephalosporins. Other causative agents are penicillins, erythromycin, co-trimoxazole, chloramphenicol and tetracyclines

-          diarrhoea is more common after antibiotics given by mouth, but can also develop after drugs given by injection (intramuscular or intravenous). The likelihood of developing the disease increases with age, however, children and young adults can be also affected

Structural changes in the colon

-          in mild disease, the colon mucosa may show only minimal inflammatory changes or swelling, or it may look quite normal. More severe inflammation is manifested by "crumbling" of the mucosa and the formation of mucosal ulcers that may mimic other intestinal inflammation. In the most severe cases, we see raised yellowish plaques covering the mucosa in the intestine. In the microscopic picture, the plaques are made up of a protein called fibrin, white blood cells and sloughed off, dead mucosal cells

Symptoms, course of the disease

-          symptoms usually begin during antibiotic treatment, less often appearing 1 to 10 days after the antibiotic is stopped, and rarely 6 weeks after the antibiotic is given

-          manifestations vary from simple diarrhoeal stools to severe colitis with bloody diarrhoea, abdominal pain and fever. In the most severe cases, loss of fluid from the body (dehydration) results in a drop in blood pressure and a decrease in urine production, which are expressions of circulatory failure; complications can also occur in the colon itself - enormous distension of the colon (called toxic megacolon) and perforation of the colon

Diagnosis

-          confirmation of the diagnosis requires examination of the stool for the presence of C. difficile toxin, or culture examination of the stool for the presence of the microbe

-          the severity of the disease is best determined by colonoscopy. As most cases affect the aboral part of the colon, it is usually sufficient to examine the colon to the extent of the rectum and the sigmoid colon. A plain X-ray of the abdomen may show swelling of the mucosa. Administration of a contrast agent into the colonic lumen (irrigography) should not be performed, particularly in severe cases, as it may contribute to perforation of the bowel

-          the cause of diarrhoea after antibiotic treatment is not clear in the absence of C. difficile; the presumed reason is reduced absorption of sugars in the presence of impaired bacterial colonisation of the gut

Treatment

-          if significant diarrhoea occurs during antibiotic treatment, the antibiotic should be stopped immediately unless absolutely necessary.  It is completely inappropriate to administer antidiarrhoeal drugs which are based on the principle of inhibiting the rhythmic contractions of the intestinal musculature (peristalsis), as this would prolong the contact of the colon with the harmful substance

-          uncomplicated antibiotic-induced diarrhoea, without signs of overt colitis or general toxicity, usually resolves spontaneously within 10 to 12 days after discontinuation of antibiotics; no further specific treatment is necessary. If mild symptoms persist, the drug cholestyramine is given to bind the bacterial toxin

-          for most post-antibiotic colitis, the most appropriate antibacterial drug is metronidazole; in the most severe cases of the disease, or when metronidazole treatment fails, the antibiotic vancomycin is given

-          in the most severe cases of the disease, hospital stay with supportive treatment with intravenous infusions and correction of the upset internal environment is necessary. Very rarely, surgical treatment is necessary to save life - removal of the colon or temporary stomia of the small intestine

Prevention

-          the best way to prevent post-antibiotic colitis is to avoid the indiscriminate administration of antibiotics and to keep the duration of antibiotic administration to a minimum