Crohn’s
disease (regional enteritis)
Crohn’s disease became widely recognised following the report in 1932
by Crohn, Ginzburg and Oppenheimer describing young adults with a chronic
inflammatory disease of the ileum. It can affect any part of the
gastrointestinal tract from the lips to the anal margin, but ileocolonic disease
is the most common presentation.
Epidemiology
It is most common in North America and northern Europe. Prevalence rates
as high as 56 per 100 000 have been reported in the UK. Over the last four
decades there seems to have been a rise in the incidence which cannot be
accounted for by increased diagnosis. It is slightly more common in females than
in males but is most commonly diagnosed in young patients between the ages of 25
and 40. There does, however, seem to be a second peak of incidence around the
age of 17.
Aetiology
Although Crohn’s disease has some features suggesting chronic
infection, no causative organism has ever been found; similarities between
Crohn’s disease and tuberculosis have focused attention on mycobacteria. Focal
ischaemia has also been postulated as a causative factor, possibly originating
from a vasculitis arising through an immunological process. A wide variety of
foods has now been implicated but none conclusively. Smoking increases the risk
threefold.
About
10 per cent of patients have a first-degree relative with the disease and there
is an association with ankylosing spondylitis. Cell-mediated immune function may
be defective in patients with Crohn’s disease but it is not known whether this
is a consequence of the disease itself or the effects of malnutrition and
medical therapy. As with ulcerative colitis it is now believed that Crohn’s
disease can predispose to cancer, although the incidence of malignant change is
not nearly as high as in ulcerative colitis and is most manifest in the ileum.
Pathology
Ileal disease is the most common accounting for 60 per cent of cases; 30
per cent of cases are limited to the large intestine and the remainder consists
of patients with ileal disease alone or more proximal small bowel involvement.
Anal lesions are common. Crohn’s disease of the mouth, oesophagus, and stomach
and duodenum are uncommon. Resection specimens show a fibrotic thickening of the
intestinal wall with a narrow lumen (Fig. 57.30). There is usually dilated gut
just proximal to the stricture and, in the strictured area, there are deep
mucosal ulcerations with linear or snake-like patterns. Oedema in the mucosa
between the ulcers gives rise to a cobblestone appearance. The transmural inflammation
leads to adhesions, inflammatory masses with mesenteric abscesses and fistulae
into adjacent organs. The serosa is usually opaque, there is thickening in the
mesentery and mesenteric lymph nodes are enlarged. The condition is
discontinuous with inflamed areas separated from normal intestine; these are
sometimes called skip lesions. Under the microscope there are focal areas
of chronic inflammation involving all layers of the intestinal wall. There are
noncaseating giant cell granulomas but these are only found in 60 per cent of
patients. They are most common in anorectal disease. The earliest mucosal
lesions are discrete aphthous ulcers. Recent studies have also shown multifocal
arterial occlusions in the muscularis propia.
Clinical
features
Presentation depends upon the area of involvement.
Acute
Crohn’s disease
Acute Crohn’s disease occurs in only 5 per cent of cases.
Symptoms and signs resemble those of acute appendicitis but there is usually
diarrhoea preceding the attack. Rarely there could be a free perforation of the
small intestine, resulting in a local or diffuse peritonitis. Acute colitis with
or without toxic megacolon can occur in Crohn’s disease but is less common
than in ulcerative colitis.
Chronic
Crohn’s disease
There is often a history of mild diarrhoea extending over many months
occurring in bouts accompanied by intestinal colic. Patients may complain of
pain, particularly in the right iliac fossa, and there may be a tender mass
palpable. Intermittent fevers, secondary anaemia and weight loss are common.
A perianal abscess or fissure may be the first presenting feature of Crohn’s
disease; the cause is often an infected anal crypt associated with concomitant
diarrhoea, but as the disease becomes chronic specific fistulae resulting from
the Crohn’s disease itself can develop.
After
months of repeated attacks with acute inflammation the affected area of
intestine begins to narrow with fibrosis causing abdominal pain on eating,
giving rise to what has been described as ‘food fear’. Children developing
the illness before puberty may have retarded growth and sexual development.
With
progression of the disease adhesions and transmural fissuring, intra-abdominal
abscesses and fistula tracts can develop.
1.Entero-enteric fistulae can occur into
adjacent small bowel loops or the pelvic colon and entero-vesical fistulae may
cause repeated urinary tract infections and pneumaturia.
2. Entero-cutaneous fistulae rarely
occur spontaneously and usually follow previous surgery.
Anal
disease (see Chapter 58)
In the presence of active disease, the penianal skin appears bluish.
Three or more oedematous pinky-blue fleshy tags protrude from the anal margin;
they may have superficial ulceration on the inner surface extending into the
anal canal. Superficial ulcers with undermined edges are relatively painless
and can heal with bridging of epithelium. Deep cavitating ulcers are usually
found in the upper anal canal; they can be painful and cause perianal abscesses
and fistulae, discharging around the anus and sometimes forwards into the
genitalia.
The most distressing feature of anal disease is sepsis from secondary
abscesses and perianal fistulae. Remarkably the rectal mucosa is often spared
and may feel normal on rectal examination. If it is involved, however, it will
feel thickened, nodular and irregular.
Investigation
Sigmoidoscopic
examination
Sigmoidoscopic examination may be normal or show minimal involvement.
Ulceration in the anal canal will, however, be readily seen.
Colonoscopy
As a result of the discontinuous nature of Crohn’s disease there will
be areas of normal colon or rectum. In between these there are areas of inflamed
mucosa which are irregular, ulcerated with a mucopurulent exudate. The earliest
appearances are aphthoid-like ulcers surrounded by a rim of erythematous
mucosa. These become larger and deeper with increasing severity of disease. In
colonic Crohn’s disease there may be stricturing and it is important to
exclude malignancy in these sites (Fig. 57.31). At the ileo-colic anastomosis of
a patient having had previous ileocaecal resection, recurrent disease is usually
seen on the ileal side of the anastomosis.
Radiology
Barium enema will show similar features to those of colonoscopy in the
colon. The best investigation of the small intestine is small bowel enema (Fig.
57.32). This will show up areas of delay and dilatation characterising
partial obstruction. The involved areas tend to be narrowed, irregular and
sometimes, when a length of terminal ileum is involved, there may be the string
sign of Kantor. Sinograms are useful in patients with entero-cutaneous fistulae.
CT scans are used in patients with fistulae and those with intra-abdominal
abscesses and complex involvement.
Treatment
Medical
therapy
Steroids are the mainstay of treatment. Patients with a relapse of their
Crohn’s disease are treated with up to 40 mg prednisolone orally, daily
supplemented by 5-ASA corn-pounds in those patients with colonic involvement,
although there is some evidence that this may help small bowel disease as well.
Those who have symptoms and signs of a mass or an abscess are also treated with
antibiotics. Azathioprine is used for its additive and steroid-sparing effect.
Nutritional support is essential. Severely malnourished people may require
intravenous feeding or nasoenteric feeding regimens. Anaemia, hypoproteinaemia,
electrolyte, vitamin and metabolic bone problems must all be addressed.
Indications
for surgery
Surgical resection will not cure Crohn’s disease. Surgery is therefore
focused on complications of the disease. As many of these indications for
surgery may be relative, joint management by an aggressive physician arid a conservative
surgeon is thought to be ideal. These complications include:
•
recurrent intestinal obstruction;
•
bleeding;
•
perforation;
•
failure of medical therapy;
•
intestinal fistula;
•
fulminant colitis;
•
malignant change;
•
perianal disease.
Surgery
To preserve functional gut length, resection is kept to a minimum so
as to deal with the local problem. The whole of the gastrointestinal tract has
to be examined carefully at the time of laparotomy. If on occasion Crohn’s
disease is diagnosed during the course of an operation for suspected
appendicitis, the appendix should be removed. If the ileum is thick, rigid and
pipe-like, senior help should be sought so that an ileocaecal resection can be
carried out.
The
course of the disease after surgery is unpredictable but recurrence is common.
It does not seem to be related to the presence of disease at the resection line.
Recurrence rates vary from site to site hut the cumulative probability of
recurrence requiring surgery for ileal disease is of the order of 20, 40, 60 and
80 per cent at 5, 10, 15 and 20 years, respectively, after previous
resection. Restorative operations have a higher incidence of recurrence than,
for example, proctocolectomy and ileostomy.
1. Ileocaecal resection is the usual
procedure for ileocaecal disease with a primary’ anastomosis between the ileum
and the transverse colon.
2. Segmental resection: short segments of small or large bowel
involvement can he treated by segmental resection.
3. Colectomy and ileorectal
anastomosis. In patients with widespread colonic disease with rectal sparing and
a normal anus this can be a useful option.
4. Temporary loop ileostomy. This
can be used either in patients with acute distal Crohn’s disease allowing
remission and later restoration of continuity or in patients with severe
penianal or rectal disease.
5.Proctocolectomy. Patients with
colonic and anal disease failing to respond to medical treatment or defunction
will eventually require a permanent ileostomy.
6.Strictureplasty. Multiple
strictured areas of Crohn’s disease (Fig. 57.33) can be treated by a local
widening procedure, strictureplasty, to avoid excessive small bowel resection (Fig.
57.34) (Lee).
7. Anal disease is usually treated conservatively by simple drainage of abscesses, placing setons around any fistulae, and occasionally in patients with inactive disease primary repair of a recto-vaginal or high fistula in ano could be attempted.
Infections
Intestinal amoebiasis. Amoebiasis is an infestation with Entamoeba
histolytica. This parasite has a world-wide distribution.
Life
history of the parasite. The active
form of the parasite or trophozoite lives in the intestinal mucous membrane
where it ingests red blood corpuscles and other cells and multiples by mitosis.
Should the parasite become pathogenic, it makes its way into the follicles of
Lieberkuhn and, by dissolving into glandular tissue via the cytolysins,
submucous loculi are produced. Some of these burst through the mucous membrane
to become amoebic ulcers. While the trophozoites continue their activities in
the base of the ulcer, others cease to feed, migrate towards the surface and
become transformed into cysts which pass into the outer world with the faeces.
Amoebiasis is transmitted mainly in contaminated drinking water.
Pathology.
The ulcers, which have been described
as ‘bottlenecked’ because of their considerably undermined edges, have a
yellow necrotic floor, from which blood and pus exude. Although on rare
occasions the ulcers are scattered throughout the large intestine, in 75 per
cent they are confined to the lower sigmoid and upper rectum.
Biopsy.
Endoscopic biopsies or fresh hot
stools are examined carefully to look for the presence of amoebae. It is
important to emphasise, however, that the presence of the parasite does not
indicate that it is pathogenic (Fig. 57.35).
Clinical
features. Dysentery is the principal manifestation of the disease but it may come
in various other guises.
Appendicitis
or amoebic caecal mass. In tropical
countries where amoebiasis is endemic, this is a constantly recurring problem.
To operate on a patient with amoebic dysentery without the precautions
subsequently described is to invite an exacerbation of amoebiasis which may
prove fatal. The bowel is friable and satisfactory closure of the appendix stump
becomes difficult or impossible, especially in cases where a palpable mass is
present. When there is an amoebic mass there tends to be tenderness on deep
palpation over the caecum and the sigmoid.
Perforation.
The most common sites are the caecum
and recto-sigmoid; usually perforation occurs into a confined space where
adhesions have previously formed and a pericolic abscess results which
eventually needs draining. When there is sudden faecal flooding in the general
peritoneal cavity, drainage of the region of the perforation, gastrointestinal
aspiration, intravenous fluid, antibiotics and a full course of emetine are
sometimes successful.
Severe
rectal haemorrhage as a result of
separation of the slough is liable to occur.
Granuloma.
Progressive amoebic invasion of the
wall of the rectum or colon, with secondary inflammation, can produce a
granulomatous mass indistinguishable from a carcinoma.
Fibrous
stricture may follow the healing of extensive amoebic ulcers.
Intestinal
obstruction is a common complication
of amoebiasis, and the obstruction is the result of adhesions associated with
pericolitis and large granuloma.
Paracolic
abscess, ischiorectal abscess and fistula occur from perforation by amoebae of
the intestinal wall followed by secondary infection.
Ulcerative
colitis. A search for amoebae should always be made in the stools of patients
believed to have ulcerative colitis.
Treatment.
High-dose intravenous steroids in this
situation can he catastrophic. Metronidazole (Flagyl) is the first-line drug,
800 mg three times daily for 7—10 days. Diloxanide furoate is best for chronic
infections associated with the passage of cysts in stools. Intestinal
antibiotics improve the results of the chronic stages, probably by coping with
superadded infection.
Typhoid
and paratyphoid. Surgical complications. Paralytic ileus is the most
common complication of typhoid.
Intestinal
haemorrhage may be the leading
symptom.
Perforation.
Perforation of a typhoid ulcer usually
occurs during the third week and is occasionally the first sign of the disease.
The ulcer is parallel to the long axis of the gut and is usually situated in the
lower ileum.
Paratyphoid
B. Perforation of the large intestine
sometimes occurs. Vigorous intravenous antibiotic therapy is given; occasionally
surgery is required to defunction the colon or in late cases remove the colon as
for ulcerative colitis.
Cholecystitis.
Acute typhoid cholecystitis is not
uncommon and perforation can occur; gallstones occasionally contain typhoid
bacilli and some patients may become typhoid carriers.
Phlebitis.
Venous thrombosis, particularly of the
left common iliac vein, is an occasional complication of typhoid fever.
Genitourinary
complications. Typhoid cystitis,
pyelitis and epididymo-orchitis may all occur.
Joints.
All degrees of arthritis, from a mild
effusion to suppuration, occur as a complication of this disease.
Bone.
Typhoid osteomyelitis and typhoid of
the spine occur.
Tuberculosis
of the intestine. Tuberculosis can affect any part of the gastrointestinal tract
from the mouth to the anus. The sites affected most often are the ileum,
proximal colon and peritoneum. There are two principal types.
Ulcerative
tuberculosis is secondary to pulmonary
tuberculosis and arises as a result of swallowing tubercle bacilli. There are
multiple ulcers in the terminal ileum,
lying transversely, and the overlying serosa is thickened, reddened and covered
in tubercles.
Clinical
features. Diarrhoea and weight loss are the predominant symptoms and usually the
patient will be receiving treatment for pulmonary tuberculosis.
Radiology.
A barium meal and follow-through or
small bowel enema will show the absence of filling of the lower ileum, caecum
and most of the ascending colon as a result of narrowing and hypermotility of
the ulcerated segment (Fig. 57.36).
Treatment.
A course of chemotherapy is given.
Healing often occurs provided the pulmonary tuberculosis is adequately treated.
An operation is only required in the rare event of a perforation or intestinal
obstruction.
Hyperplastic
tuberculosis. This usually occurs in
the ileocaecal region although solitary and multiple lesions in the lower ileum
are sometimes seen. This is caused by the ingestion of Mycobacterium
tuberculosis by patients with a high resistance to the organism. The
infection establishes itself in lymphoid follicles, and the resulting chronic
inflammation causes thickening of the intestinal wall and narrowing of the
lumen. There is early involvement of the regional lymph nodes which may caseate.
Unlike Crohn’s disease, with which it shares many similarities, abscess and
fistula formation is rare.
Untreated,
sooner or later subacute intestinal obstruction will supervene often together
with the impaction of an enterolith in the narrowed lumen.
Clinical
features. Attacks of abdominal pain with intermittent diarrhoea are the usual
symptoms. The ileum above the partial obstruction is distended, and the stasis
and consequent infection lead to steatorrhoea, anaemia and loss of weight.
Sometimes the presenting picture is of a mass in the right iliac fossa in a
patent with vague ill health. The differential diagnosis is that of an appendix
mass, carcinoma of the caecum, Crohn’s disease, tuberculosis or actinomycosis
of the caecum.
Radiology.
A barium follow-through or small bowel
enema will show a long narrow filling defect in the terminal ileum.
Treatment.
When the diagnosis is certain and the
patient has not yet developed obstructive symptoms, treatment with chemotherapy
is advised and may cure the condition. Where obstruction is present, operative
treatment is required and ileocaecal resection is best.
Actinomycosis
of the ileocaecal region. Abdominal actinomycosis is rare. Unlike intestinal
tuberculosis, narrowing of the lumen of the intestine does not occur and
mesenteric nodes do not become involved. A local abscess, however, spreads to
the retroperitoneal tissues and the adjacent abdominal wall, becoming the seat
of multiple indurated discharging sinuses. The liver may become involved via the
portal vein.
Clinical
features. The usual history is that appendicectomy has been carried out for an
appendicitis. Some 3 weeks after surgery a mass is palpable in the right iliac
fossa and soon afterwards the wound begins to discharge. At first this is thin
and watery, and then later it becomes thicker and malodorous. Other sinuses may
form and a secondary faecal fistula develop. Pus should be sent for
bacteriological examination where the characteristic sulphur granules can be
seen.
Treatment.
Penicillin or cotrimoxazole has to be
prolonged and high dosage.
Tumours
of small intestine
Compared with the large intestine, the small intestine is rarely the
seat of a neoplasm and these become progressively less common from the duodenum
to the terminal ileum.
Benign.
Adenoma, submucous lipoma and leiomyoma occur from time to time, and sometimes
reveal themselves by causing an intussusception.
The second most common complication is intestinal bleeding from an adenoma in which event the diagnosis is frequently long delayed because the tumour is overlooked at barium radiology, endoscopy and even surgery.
Peutz—Jeghers syndrome consists of:
• familial intestinal hamartomatous polyposis affecting the jejunum,
where it is a cause of haemorrhage, and often intussusception;
• melanosis of the oral mucous membrane and the lips.
The melanosis takes the form of melanin spots sometimes present on the
digits and the perianal skin, but the pigmentation of the lips is the sine qua non (Fig.
57.37).
Histology.
The polyps can be likened to trees.
The trunk and branches are smooth muscle fibres and the foliage is virtually
normal mucosa.
Treatment.
As malignant change rarely occurs,
resection is necessary only for serious bleeding or intussusception. Large
single polyps can be removed by enterotomy or short lengths of heavily involved
intestine can be resected. Those lesions within reach can be snared by
colonoscopy.
Malignant. Lymphoma. There are three main types as follows.
1.Western type lymphoma. These are annular ulcerating lesions, which
are sometimes multiple. They are now thought to he non-Hodgkin’s B-cell
lymphoma in origin. They may present with obstruction and bleeding, perforation,
anorexia and weight loss.
2.
Primary lymphoma associated with coeliac disease. There is an
increased incidence of lymphoma in patients with coeliac disease; this is now
regarded as a T-cell lymphoma. Worsening of the patient’s diarrhoea, with
pyrexia of unknown - origin together with local obstructive symptoms, is the
usual feature.
3.
Mediterranean lymphoma. This is found mostly in North Africa and
the Middle East and is associated with alpha-chain disease.
Unless there are particular surgical complications these conditions are
usually treated with chemotherapy.
Carcinoma.
As with other small bowel tumours
these can present with obstruction, bleeding or diarrhoea. Complete resection
offers the only hope of cure (Fig. 57.38).
Carcinoid
tumour. These tumours occur throughout the gastrointestinal tract, most
commonly in the appendix, ileum and rectum in decreasing order of frequency.
They arise from neuroendocrine cells at the base of intestinal crypts. The
primary is usually small but when they metastasise, the liver is usually
involved with numerous secondaries, which are larger and more yellow than the
primary, and when this has occurred the carcinoid syndrome will become evident.
The tumours can produce a number of vasoactive peptides, most commonly
5-hydrox-ytryptamine (serotonin), which may be present as 5-hydroxyindoleacetic
acid in the urine during attacks.
The
clinical syndrome itself consists of reddish-blue cyanosis, flushing attacks,
diarrhoea, borborygmi, asthmatic attacks and, eventually, sometimes pulmonary
and tricuspid stenosis. Classically the flushing attacks are induced by alcohol.
Treatment.
Most patients with gastrointestinal
carcinoids do not have carcinoid syndrome. Surgical resection is usually
sufficient. In the cases found incidentally at appendicectomy nothing further is
required. In patients with metastatic disease, multiple enucleations of hepatic
metastases or even partial hepatectomy can he carried out. The treatment has
been transformed by the use of octreotide (a somatostatin analogue) which
reduces both flushing and diarrhoea, and octreotide cover is usually used in
patients with a carcinoid syndrome who have surgery to prevent a carcinoid
crisis. Carcinoid tumours generally grow more slowly than most metastatic
malignancies; the patients may live with the syndrome of metatastic disease for
many years.