may be possible, by graClOplasty or by an artificial anal sphincter.

Inflammatory bowel disease

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel
diseases that pursue a protracted relapsing andremittingcourse, usually
extending over years. The diseases have many similarities and it is some
times impossible to differentiate between them. One crucial distinction
is that ulcerative colitis involves only the colonic mucOsa, while
Crohn's
disease can involve any part of the gastrointestinal tract from mouth to
anus. A summary of the main features of ulcerative colitis and Crohn's
disease is provided in Box 23.61.
The incidence of inflammatory bowel disease (BD) varies
widely
between populations. The highest incidence is in North America, Europe
and Oceania. A rapid increase in incidence in the 21st century
has been
seen in newly industrialised countries in Asia, Africa and South
America,
with the adoption of an increasingly Westernised lifestyle. 23
Both diseases most commonly start in the second and third
decades
of life, with a second smaller incidence peak in the
seventh decade. The
number of people with IBD over the age of65 years, however, is increas
ing, and it is becoming more common in younger children.
620000 people are affected by IBD in the UK, with a Approximately
prevalence of
0.5%-1%. Life expectancy in patients with IBD is similar to that of the
t general population. Although many patients require surgery and admis
sion to hospital for other reasons, with substantial associated
morbidity,
the majority have an excellent work record and pursue a normal life.

Pathophysiology
IBD has both environmental and genetic components, and evidence
from genome-wide association studies suggests that genetic variants
that predispose to Crohn's disease may have undergone positive selec
tion by protecting against infectious diseases, including tuberculosis
(Box 23.62). It is thought that IBD develops because these geneticaly
Susceptible individuals mount an abnormal inflammatory response to
8
environmental triggers,such as intestinal bacteria. This leads toinflam
sk mation of the intestine with involvement of a wide array of innate and
Se
adaptive immune cel responses, with release of inflammatory media
tors, including tumour necrosis factor alpha (TNF-«), interleukin (L)-12
and lL-23, which cause tissue damage (Fig. 23.55). There appears to
ay be an association between microbial dysbiosis and IBD. For example,
ally there isa reduced diversity, primarly of Firmicutes and Bacteroides,
 836 GASTROENTEROLOGY

disease
ulcerativecolitis and Crohn's
L23.61 Comparison of Ulcerative colitis Crohn's disease
Any
Any
Age group M=F
Slight female preponderance
Gender
Stable
Increasing
Any: more
Incidence Anv common in Ashkenazi Jewe
barrier function Defective innate
HLA DR103, colonic epithelial
ATG16L1, IRGMimmunity and
Ethnic group
Genetic factors (HNE4a, LAMB1, CDH)
More common in non-/ex-smokers
More common in smokers autophagy (NO02
Risk factors Appendicectomy protects
with variable Any part of
Colon only; begins at anorectal margin gastrointestinal tract,
Anatomical distribution proximal extension COmmon; patchy
Common
distribution, skip perlesiiaonalns disease
Extra-intestinal manifestations Common
Bloody diarrhoea Variable: pain, diarrhoea, weight \oSs al
Presentation
Inflammation limited to mucosa; crypt distortion, Submucosal or transmural common
Histology cryptitis, crypt abscesses, loss of
goblet cells deep fissuring ulcers,
fistuli
anfl
e,am ma tion
patchy commony
granulomas

Gucocort icoi ds,

charges,
5-ASA; gluCOCorticoids; azathioprine; biologic azathiopri ne;
Management
therapy (anti-TNE; anti-a4ß7 integrin,
anti-p40, therapy (anti-TNE, anti-a4p7 methotrexate: birlone
integrin, anti-pán
Janus kinase inhibitor); colectomy iscurative nutritional therapy; smOKINg cessation;
complications is not t
Curative:5-ASA0ssurgery for
not effective.
5-ASA = 5-aminosal1icylic acid; TNF = tumour necrosis factor)

23.62 Factors associated with the development of

inflammatory bowel disease
Genetic
" Both CD and UC are common in AshkenaziJews
" 10% have first-degree relative/one or more close relative
with IBD
M cll
identical twins (40%-50% CD; 20%-25% UC)
" High concordance in
significance; most
" 163 Susceptibility loci identified at genome-wide levels of
to both CD and UC; many are also susceptibility loci for
Confer susceptibility
other inflammatory conditions (especially ankylosing spondylosis and psoriasis) 2
HLA locuS, and with
" UCand CD are both associated with genetic variants at
IL-10
multiple genes involved with immune signaling (especially IL-23 and APC)
pathways) Type 1
autophagy (NOD2,
CD is associated with genetic defects in innate immunity and
Th cell
ATG16L1 and RGM genes) IL-1
function IL-6 IL-12
" UC is associated with genetic defects in barrier TNF-a IL-23
NOD2 is associated with ileal and stricturing disease, and hence a need for
" release
resectional surgery IFN-y
" HLA-DR"103 is associated with severe UC
Environmental
" UC is more common in non-smokers and ex-smokers Macrophage
" CD is more common in smokers (relative risk = 3)
"CD is associated with a low-residue, high-refined-sugar diet
disease. (1) Bactenal aniges
Fig. 23.55 Pathogenesis of inflammatory bowel epithelial cells or enet
Commensal qut microbiota are altered (dysbiosis) in CD and UC
between leaky
"Appendicectomy protects against UC are taken up by specialised Mcells. pass
After processing, they are preseled
lamina propria through ulcerated mucosa. (2)
(CD = Crohn's disease: HLA = human leucocyte antigen; IBD = inflammatory bowel disease; antiaen-oresenting cells (APCs) in the lamina propla.
tO type 1 I-helper cells by CoeFurther
L= intereukin; UC = ulcerative colitis) differentiation results in a Th. Tcell-mediated(FNy).
(3) 1-cell activation and interferon gamma
response (4) with secretion of cytokines, including actvationofno-
process with
amplification of Tcells perpetuates the inflammatory including interleukin(-12
and a relative increase in Enterobaceteriaceae. Functional changes in immune cells and release of other important cytokines, (TNF-a). These pathways
sel-limitingin
the bacteria are important and include a reductíon of anti-inflamma
IL-23, IL-1, IL-6 and tumour necrosis factor alpha andthisis immunity
insult
in all normal individuals exposed to an inflammatory dysregulationofinnate
tory metabolites, such as butyrate and other short-chain faty acids. healthy subjects. In genetically predisposedI persons,
While microbial dysbiosis has been recognised in IBD, a causal role may trigger inflammatory bowel disease.
has yet to be established. There is emerging evidence that the virome
and mycotbiome (fungal species) may be important in the development spreacs
of IBD. In both diseases, the intestinal wall is infitrated with acute and Ulcerative colitis and
rectum (proctitis) colonin
some
chronic inflanmatory cells, but there are important differences between Inflammation invariably involves the involvethe can
entire become
the conditions in the distribution of lesions and in histological features proximaly in a continuous manner to bowel
pancolitis. the
(Fig. 23.56). cases (pancolitis). In long-standing
 Ulcerative
colitis

Proctitis Left-sided colitis Extensive colitis

40-50%% 30-40% (up to pancolitis)
20%

Crohn's
disease

lleal or ileocolonic Small intestinal Crohn's colitis Perianal disease alone

40% 30-40% c. 20% <10%

Common patterns of disease distribution in inflammatory bowel disease.

Fig. 23.56

Ahodened and post-inflammatory pseudopolyps' develop: these

ommal or hypertrophied residual mucOsa within areas of atrophv
to the mucosa and
Eo 23.57). The intlammatory process is limited
23.58). Both acute and
snares the deeper layers of the bowel wall (Fig.
ohronic inflammatory cells infiltrate the lamina propria and the crypts
'enotitis'). Crypt abscesses are typical. Goblet cells lose their mucus
Dysplasia., char
and. in long-standing cases, glands become distorted.
acterised by heaping of cells within crypts, nuclear atypia and increased
mitotic rate, may herald the development of colon cancer.
Crohn's disease
The sites most commonly involved, in order of frequency, are the terminal
leum and right side of the colon, the small intestine, the colon alone, and
the perianal region (Fig. 23.56). The entire wall of the bowel is oedema
tous and thickened. and there are deep ulcers that often appear as linear
fissures; thus the mucosa between them is described as 'cobblestone' 23
These may penetrate through the bowel wall to initiate abscesses or
IStulae involving the bowel. bladder. uterus, vagina and skin of the per
neum. The mesenteric lymph nodes are enlarged and the mesentery is
UcKened. Crohn's disease has a patchy distribution and the inflamma Fig. 23.57 Pseudopolyposis in ulcerative colitis.
Uy process is interrupted by islands of normal mucosa, resulting in 'skip
sos, On histological examination, the bowel wall is thickened with a
utonic inflammatory infiltrate throughout all layers (Fig. 23.59).

Clinical features
Ulcerative colitis
The
and blcardinal Symptoms are rectal bleeding with passage of muCus
oody diarrhoea. The presentation varies, depending on the site
ad severity of the
disease (see Fig. 23.56), as well as the presence of
andextrisa-intestinal I manifestations The first attack is usually the most severe
rent fol owed by relapses and remissions. Emotional stress, intercur-
voke inferelapse.
ction, gastroenteritis, antibiotics or NSAID therapy may all pro-
accompani Proctitis
d ed by tenesmus. Some patients pass frequent, small-volume
causes rectal bleeding and mucus discharge,
of thestools, while
otherS pass pellety stools due to constipation upstream
and inflamed rectum. Constitutional Ssymptoms rarely occur. Left-sided SM

todominal extensivCramps.
e colitisIn causes bloody diarrhoea with mucus, often with
dSiogdnsomiofnail pan 0cCur and the cases
severe anorexia, malaise, weight loss and
patient is toxic, with fever, tachycardia and
Fig. 23.58 Histology of ulcerative colitis. There is surface ulceration and
inflammation is confined to the mucosa with excess inflammatory cells in the lamina
peritoneal inflammation (Box 23.63). propria, loss of goblet cells and crypt abscesses (arrows). (SM= submucosa)
 838 " GASTROENTEROLOGY

Crohn's disease of
Crohn's disease. Many
bowel andcolonic [Link]
The major symptoms are abdominal pan, diarhoea and weight loss. Afew oresent
with
dlisease, vomiting from jejunal patients present
leal Crohn's disease (Figs. 2360 and 23.61) may cause subacute or
even acute intestinal obstruction. Patients Can occasionally present with strictures syptoraol ms
Physical exarmination often reveals severe
or
a pertorated abscess. Abdomnal pain is often associated with diarhoea,
which is usually watery and does not contain blood or mucus. Patients
with glossitis and angular
most marked over the st
inflamedomat it
[Link]. evidence
There of
ulcealin
is weight
may lose weight because they avoid food, since eating provokes pain.
Weight loss may also be due to malabsorption and some patients pres
ent with features of fat, protein or vitamin deficiencies. Crohn's colitis
ble and is due tomatted loops of
abscess. Perianal skin tags.
of patients.
An
fissuresthicorkened
abdor inal
abdOminal mass tende
fistulaebowelare or an
presents in an identical manner to ulcerative colitis, but rectal sparing Differential diagnosis
and the presence of perianaldisease are features that favour a diagnosis The differential diagnosis is:
tant issue is to distinguishthe first
In general, diarrhoea lasting
Summarattack
ised in Box 23.64 The
of
acute
daysain colWestitise fromrnos
A
longer
unlikely to be the result of [Link] 10 ro
antibiotic exposure (Clostridioides whereas history of irterhir
difiincvesle/[Link]
tis) or homosexual contact
should be excluded by the increases the
appropriate possibility of
(see
Trs

SM

Fig. 23.59 Histology of Crohn's disease.A Inflammation is 'transmural'; there is Fig. 23.60 lleal Crohn's disease. Small bowel magnetic
fissuring lceration (arrow), with inflammation extending into the submucosa (SM). resonance image showng
a terminal ileum that is thickened, narrowed and enhancing (arrow), with
B At higher power, a characteristic non-caseating granuloma is seen. diataton
immediately proximal to this.

23.63 Assessment of disease severity in ulcerative colitis

Mild Moderate Severe
Daily bowel frequency <4 4-6 >6*
Blood in stools +/ +/++ +++
Stool volume < 200 g/24 hrs 200-400 g/24 hrs >400 g/24 hrs
Pulse <90 beats/min 90 beats/min >90 beats/min
Temperature Normal Normal >37.8°C*
Haemoglobin Normal 10g/dLj*
Normal < 100g/L (<
Erythrocyte sedimentation rate Normal
Normal > 30mm/hrt (or equivalent
C-reactive protein)
Serum albumin
>35g/L (> 3.5 g/dL) <30g/L (< 3g/d) isands
Abdominal X-ray Normal bowel. mucosal
Normal Dilated orabsent
numb-printinaofmucosa,
of features
Sigmoidoscopy SeveremucOsalinflammatory
Normal or erythema/granular mucosa lumel
ulceration:boodin
Changes:
*The Truelove -Witts criteria for acute severe
ulcerative colitis are >6 bloody stools/24 hrs plus one or markers.
more of: anaemia, fever, tachycardia and highhinflammatory
 Inflammatory bowel disease

23.65 Differential diagnosis of small bowel Crohn's disease

Other causes of right illac fossa mass:
Caecal carcinoma
Appendix abscess*
Infection (tuberculosis, Yersinia, actinomycosis)
Mesenteric adenitis
Pelvic inflammatory disease
" Lymphoma
*Common; other causes are rare.

02 61 Barium follow-through showing terminal ileal Crohn's disease.

proximally there is ulceration with
Aon0 stricture is present (arrow A), andB).more
(arrow
characteristic 'rose thorn' ulcers

23.64 Conditions that can mimic ulcerative or Crohn's colitis

Infective
Bacterial
" Gonococcal proctitis
" Salmonella
" Pseudomembranous colitis
Shigella Chlamydia proctitis
" Campylobacter jejuni
" Escherichia coli 0157
Viral
"Herpes simplex proctitis " Cytomegalovirus colon due to
Fig. 23.62 Plain abdominal X-ray showing a grossly dilated 'thumb
Protozoal severe ulcerative colitis. There is also marked mucosal oedema and
" Amoebiasis printing' (arrows).
Non-infective
Ischaemic colitis " Diverticulitis
Collagenous colitis " Radiation proctitis Fistulae
"Non-steroidal anti-inflammatory " Behçet's disease can cause 23
" Colonic carcinoma These are specific to Crohn's disease. Enteroenteric fistulae
drugs EnterOvesical
diarrhoea and malabsorption due to blind loop syndrome.
fistulation causes recurrent urinary infections and pneumaturia. An enter
dagnosis of Crohn's disease is usually more straightforward and
is Ovaginal fistula causes a faeculent vaginal discharge. Fistulation from the
fissures and
made on the basis of imaging and clinical presentation, but atypical bowel may also cause perianal or ischiorectal abscesses,
cases biopsy or surgical resection is necessary to exclude other dis fistulae.
eases (Box 23.65).
Cancer
ulcerative coli
Complications Colorectal cancer accounts for one in six deaths in
with the duration and
Lie-threatening colonic inflammation tis. The risk of dysplasia and cancer increases
patients who have
Ihis can ocCur in both ulcerative colitis and Crohn's colitis. In the most extent of uncontrolled colonic inflammation. Thus therapy
at highest risk. 5-ASA
rreme cases, the colon dilates (toxic megacolon) and bacterial toxins long-standing, extensive colitis are
neoplasia in ulcerative colitis.
báss freely across the diseased mucosa into the portal and then sys may reduce the risk of dysplasia and colorectal cancer in ulcer
Thiopurines alsO seem to reduce the risk of
eic circulation. This complication arises most commonly during the However, these benefits must
S attack of colitis and is recognised bythe features described in Box ative colitis, but not Crohn's disease.
be weighed against the very small increase in lymphoma, especially in
00. An abdominal X-ray should be taken daily because, when the cumulative incidence for IBD-associated colorectal
older patients. The
ransverse Colon is dilated to more than 6cm (Fig. 23.62), there is a high
risk of colonic perforation, although this Complication can also occur in cancer has been reported at 1% at 10 years after
diagnosis, which
risk is par
the absence of toxic megacolon. Severe colonic inflammation with toxic increases to 7% after 30 years. For unknown reasons, the
chol
dilatation is asurgical emergency and often requires colectomy. ticularly high in patients who have concomitant primary sclerosing
areas of dysplasia and may be multiple.
angitis. Tumours develop in
Haemorhage Patients with long-standing colitis are therefore entered into
lance programmes beginning 8 years after diagnosis, with
surveil
patients with
botHah emconditions,
orrhage This is
due to erosion of a major artery is rare, but can occur in colonoscopy
more common in Crohn's disease, where deep primary sclerosing cholangitis having annual surveillance
lceration erodes larger vessels. from diagnosis. Targeted biopsies of areas that show abnormalities on
 840 GASTROENTEROL0GY

staining with indigo camine or methylerne blue increase the chance Bacteriology
ofdetecting dysplasia and this tochnique (temed pancolonic chromo At initial presentation, stool
endoscoy) has replaced colonosoopy with random biopsies taken
every 10cm in screening for malignancy The procedure allows patients
Clostridiodes difficile toxin
serological tests should ova
be performer
or miforcroscopy,andcultcysts,
ure and
to be stratified into hioh, mdium or iow risk groups to determine repeated in established disease to blc
excludeTheseSuperinivmesp0Sed examinat
oftigations
the interval between suveillance procedures. Family history of colon tion in patients who present
with
cancer is also an important factor to consider. If high-grade dysplasia
is found, panproctocolectomy is usually recommended because of the
high risk of colon cancer
flares necessitating hospital admission.
should be sent for bacteriology to exacerbations
maximitsheree separate stoencter , tes,
Extra-intestinal complications Endoscopy sensitivty
Extra-intestinal complications are common in lBD and may dominate the Patients who present with diarrhoea
clinical pcture Some of these occur during relapse of intestinal disease; or alarm features, such as plus raised inflamr
weight loOSs, rectal
others anpear to be unrelated to intestinal disease activity (Fig. 23.63). should undergo ileocolonoscopy. Flexible
diagnosis, mayespeciallyble ding andis anaeri
nmalony mate
Investigations
Investigations are necessary to confim the diagnosis, define disease
ally performed to make a
presentations wheni
ileocolonoscopy should ileocolonoscopy
stil be confer duingsigmoidoSCopy
performed at a lateran acute se rsy
distnbution and activity, and identfy complications. Full blood count may
showanaemia resuting from bleeding or malabsorption of iron, folic acid
or vitamin B,. Platelet count can also be high as a marker of chronic
order to evaluate disease extent. In
unac eplatle
cular pattern, granularity, friability andulcerative colitis, date.,is howeNe
ulceration (Fig. 23.64). In Crohn's Contact bleedinthg,ere withlosSot of vas
discrete, deep ulcers, strictures anddisease, patchy
often with rectalinfl(afms mauretsio, n, lae.
infammation. Serum albumin concentration falls as a consequence of
protein-Iosing enteropathy. inflammatory disease or poor nutrition. ESR and skin tags), is typically observed, perianal disease wrth
ist
and CRP are elevated in exacerbations and in response to abscess
fomation. Faecal calprotectin has a high sensitivity for detecting gas
lished disease, colonoscopymay show
polyps or a complicating carcinoma.
vactive inflammatsparioning, In estat
trointestinal inflammation and may be elevated, even when the CRP is anatomical segment (terminal ileum, right Biopsies should be takenwith pseut
nomal. It is particularly useful for distinguishing inflammatory bowel dis colon and rectum) to confirnm the colon, transverse from ea
diagnosis and define
andingdsease
ease from irritable bowel syndrome at diagnosis, and for subsequent and also to seek dysplasia in patients
with
monitoring of disease activity. by pancolonic chromo-endoscopy. In Crohn's long-stdisease, coitis etent
wireless squded
Cansue

Occur during the active phase of Unrelated to inflammatory

inflammatory bowel disease bowel disease activity
Conjunctivitis
Iritis
Episcleritis Autoimmune hepatitis
Mouth ulcers

Primary sclerosing cholangitis

and cholangiocarcinoma
Fatty liver (ulcerative colitis)
Liver abscess/portal pyaenia Gallstones
Amyloidosis and oxalate calculi

Mesenteric or portal vein thrombosis

Sacroilitis/ankylosingspondylitis
(Crohn's with HLA-B27)

Venous thrombosis Metabolic bone disease

Large-joint arthritis

Erythema nodosum

Pyoderma gangrenosum

Fig. 23.63 Systemic complications of inflammatory bowel disease. See also Chapters 24 and 26. (HLA = human leucocyle age
 atory bowel disense B41
23,66 Non-biologio
Class
Intlammatory bowel agents
diseaseused in the troatment of
Drug Indication
Aminosalicylates Mesalazino
Olsalazine
Induce romission or
maintenance in mild/
Sultasalazine
Balsalazide moderate ulceratlve
Glucocorticoids colitis
Prodnisolone Induce remission in
Hydrocortisone acute ulcerative colitis
Budesonide or Crohn's clsease
Beclomethasone
Anti-metabolites
Metthylprednisolone
Azathioprine Maintenance therapy
mocua Mercaptopurine in ulcerative colitis or
Crohn's disease
Methotrexate Maintenance therapy in
Crohn's disease
Calcineurin inhibitors Ciclosporin Severe ulcerative
Sigmoidoscopic view of moderately active ulcerative colitis.
enthematousandfriable with contact bleeding. Submucosal blood vessels
colitis refractory to
s visIble
Masanger glucocorticoids
JEnO Antibiotics
Ciprofloxacin Peri-anal Crohn's
Metronidazole disease and pouchitis
sensitivity for detecting small bowel disease
enoscopyhas a greater
comoarisonto radiological techniques
and is useful when there is a roles in education, reassurance and coping. The key
n despite normal imaging. Enteroscopy may be aims of medical
suspicion of Crohn's therapy are to:
hah to make a histological diagnosis of smalll bowel Crohn's disease,
RUTed
" treat acute attacks (induce
whenthe inflamed segment is out of reach of standard endoscopes, or remission)
" prevent relapses (maintain remission)
indication, such as dilatation of strictures. In individuals
bratherapeutic " prevent bowel damage
nner gastrointestinal symptoms, an upper gastrointestinal endos " detect dysplasia and prevent carcinoma
May be useful. However, this is not routinely used in adults with select appropriate patients for surgery.
disease.
SISDected or proven Crohn's
Radiology Medical therapy
Where colonoscopy is incomplete, a CT colonogram is preferred, Small Several medical treatment options exist in the management for IBD.
el imaging is essential to complete staging of Crohn's disease. Whilst traditional management for IBD has been through the use of
Tadtionl contrast imaging by barium follow-through denmonstrates non-biologic treatments, there has been a rapid expansion in the use of
sftected areas of the bowel as narrovwed and ulcerated, often with mul biologics, with common treatments described below.
re stictures (see Fig. 23.61). This has largely been replaced by MRI
gnterography, which does not involve exposure to radiation and is a sen Non-biologic therapies
stive way of detecting extra-intestinal manifestations and of assessing Non-biologics used in IBD are summarised in Box 23.66. 23
pevc and perineal involvement. These studies use an orally adminis
ed smallbowel-distending agent and intravenous contrast to provide Aminosalicylates (5-ASA)
TaSmUral imaging that can usefuly distingish between predominantly 5-ASAs are more commonly used in ulcerative colitis than in Crohn's
rfammatory strictures (that should respond to anti-inflammatory medi disease. 5-ASAs are thought to have multiple anti-inflammatory effects,
a strategies) and fibrotic strictures (that require a mechanical solution, including inhibition of mediatiors of lipoOxygenase and cyclo0xygenase,
SJCh as surgical resection, stricturoplasty or endoscopic ballOon dilata modulating cytokine release from the mucOsa. Several types are availa
m. Aplain abdominal X-ray is essential in the management of patients
MO present with severe active disease. Dilatation of the colon (see
ble, with diferent means of delivery to the colon; pH-dependent (Asacol,
Salofalk), time-dependent (Pentasa) or bacterial breakdown bycolonic
79 23.62), mucosal oedema (thumb-printing) or evidence of bacteria from a carrier molecule (sulfasalazine, balsalazide). While sul
perfora
ay De fOund. Patients with proctitis may have features of fasalazine was the first 5-ASA to be used in IBD, side-effects are com
proximal
a oa0ing. In small bowel Crohn's disease, there may be mon, such as headache, nausea, diarrhoea and blood dyscrasias. Other
evidence
estinal otbstruction or displacement of bowel loops by a 5-ASAs are better tolerated. 5-ASAs can be administered oraly or top
Duno is a very powerful tool to detect small bowel mass.
ad stricture inflammation ically (suppositories or enema). Patients commencing a 5-ASA should
formation,
nted to sCreening for but it is operator-dependent. The role of CT is have their urea and electrolytes checked at baseline, after 2-3 months
Imation, in the acutely complications,
unwel.
such as perforation or abscess and then annually, as nephrotoxicity can occur rarely (1 in 4000 patient
years).
MaMWenicaalgetmheernapty plays an important role in the mannagement of IBD.
Glucocorticoids
Glucocorticoids such as prednisolone, hydrocortisone, budesonide and
optimal
tesapmec-biaalissetds management
ery beclomethasone can be used to induce clinical remission in both ulcer
depends on establishing a multidiscipli-
MSe approach involving physicians, surgeons, radiologists, ative colitis and Crohn's disease, but have no role in preventing relapse.
and dietitians. Both ulcerative colitis and Crohn's dis- They can be administered orally, topically (suppositories or enema) or
|
Ins,
speciaist nurConditions and have
ses, Counsellors and important
psychosocial implica-
patient support groups have key
intravenously and have powerful anti-inflammatory effects. When admin
istered, it is important to have high vigilance for complications, such as
 842 " GASTROENTEROLOGY

calcium and vita Anti-TNF antibodies

osteoporosis,diabetes andweight gain, SimultaneouS These include infliximab.
min Dsupplementation should be
is a potent glucocorticoid, which
given
is
for bone
efficienty
protection. Budesonide
cleared from circulation by They are monoclonal antibodies adalimumab,
golimtoumabTNF and
that bind
inflammatory and pathological cytokine
the liver, thereby minimising adrenocortical
suppression and
It is commonly considered for active ileitis and
ileocolitis.
side-effects.
(anaphylactic) and delayed (serum
occur after multiple infusions. sickness)
-a,
release by DTNE-reyerting
also measured to Anti-drug antiinbfusion cerolzurnak, ro
assess ody trreesactionS
levels oan be
Can
infection; [Link] Anti-
Thiopurines ies are contraindicated in
Thiopurines used in IBD are azathioprnine and mercaptopurine.
They are
losis and moderate to severe of INF and dhg
failure can latent antit
Azathioprine and mer
immunnmodulators that induce T-cell apoptosis. cardiac
this, assessment for latent tuberc
There is a hepatitis \ubera
to thioguanine
to commencement is required. ulosis and
captopurine are administered orally and metabolised
nucleotides (TGNS). Thiopurine methyltransferase (TPMT) methylates thi
opunine metabolites away from TGNs and affects drug levels.
Leucopenia of malignancy and, rarely.
should occur until treatmentneurological adverse
possible
can occur in 3%, particularly in inherited TPMT
deficiency. TPMT levels
are checked prior to starting treatment and thiopurines
are avoided if 12 months.
failure, or should [Link]ñ
deficientvery low due to risk of
after starting treatment to be
toxicity.
effective.
Thiopurines
Around 20%
take
of
around
patients
6 weeks
will have Anti-a4p7 integrin
Vedolizumab is a monoclonal
reas es ed aftex
complications leading to drug withdrawal. Complications include influen antibody that
za-like syndrome with myalgia, nausea and vomiting. Genetic variation of
NUDT15 has been described in association with myelosuppression and
expressed on leukocytes and inhibits
leukocyt
gut-specific receptor on endothelium, reducing ebloicksnteracta4ETion integrn
testing is performed if available. Other adverse effects include hepatotox qut mucOsa. It is a gut-selective
and Crohn's disease. Side-effectss
biologic used inleukocyt
bothe migration nto
ioity and pancreatitis. Patients are counselled on the increase lymphoma include ulceraive colis,
(approximately 2-3-fold) and non-melanoma skin cancer (life-long sun
protection advised) risk. Caution is taken in prescribing thiopurines in
patients presenting over the age of 60 years due to risk of malignancy.
Methotrexate
headache. Treatment is discontinued if
14 weeks. Treatment should occur until
reassessed after 12 months.

Janus kinase inhibitor

nasopharyngits,arhralga rd
there is no
improvement
treatment failure, or
nt ater
shoud be
Methotrexate can be used for maintanence therapy in Crohn's disease, Tofacitinib is a Janus kinase inhibitor that
with no role in ulcerative colitis. It is commonly used in individuals who Janus-associated tyrosine kinases JAK1 andselectively inhibits the
have failed to respond with thiopurines. It is a folic acid antagonist, which inflammatory cytokine signalling via the STAT JAK3, blocking pro-
inhibits dihydrofolate reductase, preventing DNA synthesis. The bio advantage of oral administration in pathtoway. It has the
availability of oral methotrexate is variable when compared to parental comparison
ics being used in ulcerative colits. High doses should other bidlog-
in patients at risk of pulmonary be
administration, with the subcutaneous injection being generally preferred embolism and it is contraindaod avoided
to intramuscular due to ease of administration. Nausea, stomatitis, diar in pregnancy. Herpes zoster has been noted to occur more
rhoea, hepatotoxicity and pneumonitis can occur with methotrexate. active treatment;zoster vaccination is therefore often on
Folic acid should be given concurrently to reduce gastrointestinal and over age of 70 years or high-risk individuals recommendedin thosa
(recurrent shingles) oyer
liver toxicity. Women of child-bearing potential must use a robust con 50 years.
traceptive method and should be counseled to plan pregnancy with a
6-month methotrexate-free period prior to conception as it is teratogenic. Anti-p40 antibodies
Ustekinumab is a monoclonal antibody that binds to p-40 subunit of
Ciclosporin both IL-12and IL-23 to prevent T-cell activation; it is used in both ucer
Ciclosporin is a calcineurin inhibitor, inhibiting in particular the transcrip ative colitis and Crohn's disease. Side-effects include nasopharyngt's.
tion of interleukin-2. It is used in ulcerative colitis that has responded headache and arthralgia. Treatment should occur until treatment failue
poorly to glucocorticoids and has no role in Crohn's disease. Major or should be reassessed after 12 months.
side-effects indlude nephrotoxicity, infections and neurotoxicity (including
fits). Minor complications include tremor, paraesthesiae, abnormal liver Therapeutic drug monitoring
function tests and hirsutism. Acutely, ciclosporin is usually administered Up to one-third of patients do not respond to biologic therapy (or
intravenously, with responders to treatment converted to oral admin mary non-response), with up to a half discontinuing biologic therapy
istration, which is continued for several months as a bridging therapy. after initial response due to secondary loss of response or advese
Thiopurine manintence therapy is commonly given as maintanence sub effects. This can be due to pharmokinetic or pharmodynamic sSe
sequently, as ciclosporin has no benefit as maintenance therapy of the drug. Favourable outcomes have been associated win 9
drug concentrations, with low levels leadina to immunogenicity au
Antibiotics drug tailure. Therapeutic drug monitoring can be performed WIU
Antibiotics are useful in peianal Crohn's disease and pouchitis. There pree
logic therapy, ensuring patients have adeauate drug levels, treatment
is little evidence comparing different antibiotics for acute pouchitis, levels. Combination
tively preventing flares due to low drug
although ciprofloxacin is better tolerated with fevwer adverse effects than of biologics with thiopurines or methotrexate can be Useu alsobe
metronidazole. The major concern is peripheral neuropathy with long monitoring can
vent and reduce anti-drug antibodies. Drug metabolites measuredto
term metronidazole, with tendon inflammation and damage potentially
performed with thiopurines, with thiopurine
OCcurring with ciprofloxacin. Combination antibiotics may be needed for tailor therapy.
chronic pouchitis. Antibiotics tend to be used in combination with thio
purines and anti-TNF therapyin perianal disease. Ulcerative colitis
Active ulcerative colitis treatedwvithtoolcalorord
Biologic agents Patients with active ulcerative colitis areeinitially or
extensie

Several classes of biologic agents are used in the Patients with left-sided prevent
termto
IBD, with their indication shown in Box 23.67 and site management
of 5-aminosalicylate (5-ASA) therapy. inthe long
of action shown
in Fig. 23.65. The majority of biologics are administered either ulcerative colitis should continue oral 5-ASA Individuals with ansysten
with
intra relapse and minimise the risk of dysplasia. treatmentGlucocortcotS
venously or subcutaneously, with the exception of tofacitinib, which plete response to 5-ASA treatment may
require
is administered orally. therapy.
glucocorticoids,immunomodulator or biologic
 Inflammatory

Lumen
-Antigen
Epithelium
T cell Anti-TNE
Dendritic
cell IL-12 TNF
Macrophage

IL-23 Anti-p40
Lamina propria
T cell
Janus
Multiple T cell kinase
cytokines inhibitors
MAdCAM-1 T cell e.g. IL-21

Anti-a4B7
integrin
Blood vessel RBC
RBC

T cell

of action of biologics. (TNF tumour

= necrosis factor; IL =interleukin; RBC =red blood cell)
Fig. 23.65 Site

inflammatory
23.67 Biologic agets used in the treatment of Active ulcerative colitis
bowel disease
Drug Indication
Class
Anti-TNF antibodies Infliximab Moderate to severe
Crohn's disease and
ulcerative colitis
Acute severe ulcerative Left-sided or extensive
Proctitis ulcerative colitis
colitis as rescue
therapy
Adalimumab Moderate to severe
Crohn's disease and
ulcerative colitis
Golimumab Moderate to severe
Oral 5-ASA and
ulcerative colitis 5-ASA suppository
(usually at night) 5-ASA enema
23
Certolizumab Moderate to severe
Crohn's disease
Moderate to severe Incomplete
Anti-a4ß7 integrin Vedolizumab response
Crohn's disease and
ulcerative colitis
Addition of oral 5-aminosalicylate Incomplete
Janus kinase Tofacitinib Moderate to severe therapy. Consider glucocorticoid
ulcerative colitis suppository if intolerant of 5-ASA response
inhibitor
suppository but less effective
Anti-p40 antibodies Ustekinumab Moderate to severe
Crohn's disease and
Incomplete
ulcerative colitis response

Oral prednisolone
Snould never be used for maintenance therapy. Analgorithm for the man (40 mg daily, tapered
agement of active ulcerative colitis is shown in Fig. 23.66. by 5 mg/week over
8-week course)
Severe ulcerative colitis Incomplete
Patients who fail to respond to maximal oral therapy andthose who pres- response
l With acute severe colitis (meetina the Truelove-Witts criteria; see Box
23.63) are best
managedin hospital and should be monitored jointly by
a
physician and surgeon: Immunomodulator/
biologic therapy
clinically: for the presence of abdominal pain, temperature, pulse
rate, stool blood and Fig. 23.66 Medical management of active ulcerative colitis.
frequency
 844 " GASTROENTEROLoGY

23.69 Monitoring of
2368 Medical management of
tulinant ulcerative colitis inflammatory bowel disease
" Admit to hospital for intensive therapy and
monitoring
" Assess symptoms, Including extra-
intestinal manilestations
Eyamine for abdominal mass or perianal disease
(B0)
" GheVfluids and corect electrolte inbalance " Pertorm full blood count, urea and
is < 1000l (<10g'd) electrolytes, liver
" Consider transtusion it haemoglobindaily)
" Gve Nmethviprednisolone (60mg
or hydrocortisone (100 mgour times
C-reactive protein (CRP)
" Check haomatinics (vitamin B,,folate, Iron tunction tests,
studies) least altxumin,
" Check faecal calprotectin (to monitor each disease at
daily)
annually
" Gie antibiotics untlenteric infecton is
" Arange nutritonal supoort
" Gve subutaneous
excluded

low-molecular-weight heparin for prophylaxis of venous

assess response)
" Perform stool cultures (at each flare to exclude
Assess mucosal healing:: Surrogate markers
(larelchange
infection)
in
Theracoy an
thromboembolism
" Avoid opiates and antidianhoeal agents
" Consider infiximab (5ma ka)or ciclosporin
(2 mg/ka) in stable patients not
capsule, ileocolonoscopy and/or small bowel
" Enrol patient in a dedlcated IBD clinic
(monitoring(CRP/[Link])n,ce
magnetic
of
small bowel
patients may be carried out by a nurse or phone clinicstable, imanjing
responding to 3-5 days of glucocorticoids " Arrange lBD multidisciplinary
" Check vaccinations are up to
meeting for acutely ill or
date; live cormplex
uncomplicates
ther and at leastgivpat
N=ntaenous) vaccinations may be ients
weeks before starting immunosuppressive therapy en at least 4
stopping immunosuppressive therapy. Patients on (3 monthis ater

count, albumin, elec

should receive influenza andpneumOcoccal vaccination
" Ensure Surveillance colonoscopy is scheduled where immunosup res ive IheraN
appropriate
by laboratory testing: haemoglobin, white cell
including Clostridioides dificile
trolytes, ESR and CRP stool culture,
toxin assay Crohn's disease
radiologicaly: for colonic dilatation on plain abdominal X-rays. Principles of management
intravenous flu Crohn's disease is a progressive condition that may
Allpatients should be given supportive treatment with result in
imporinducetantsticure
pro fistula formation if suboptimally treated. It is therefore or
ids to corect dehydration and enteral nutritional support should be long-term treatment goals with the patient; these are to to agree
vided for malnourished patients (Box 23.68). Intravenous glucocorticoids
normalrqality
emission
and then maintain glucocorticoid--free remission with a
(methylprednisolone 60mg every 24 hours or hydrocortisone 100mg
life. Treatment should focus on monitoing the patient of
four times daily) should be given by infusion or bolus injection. Patients carefuly for ei-
dence of disease activity and complications (Box
should receive prophylactic low-molecular weight heparin, as the risk that mucOsal healing is achieved. 23.69), and ensuring
of venous thromboembolism is 2-3-fold higher compared to inpatients
without lIBD. Topical and oral aminosalicylates have no role to play in
Induction of remission in mild to moderate dsease
the acute severe attack. Response to therapy is judged over the first 3
days. Patients whodo not respond promptly to glucocorticoids should
Glucocorticoids remain the mainstay of treatmernt for active Crohn's dseasa
be considered for medical rescue therapy with ciclosporin (2 mg/kg daily The drug of first choice in patents with ileal disease is budesonide sinooà
by intravenous infusion followed by 5mg/kg daily, then orally after 7 days)
undergoes 90% first-pass metabolism in the lver and has very litle se.
or infiximab (5mg/kg), which can avoid the need for urgent colectomy in temic toxicity. Atypical regimen is 9mg once daily for 4 weeks, wih asteo
approximately 60% of cases. wise reduction of 3mg every 4 weeks untl therapy is stopped. If there sm
Patients who develop colonic dilatation (> 6cm), those whose clinical response to budesoide within 2 weeks, the patient should be switcheai to
and laboratory measurements deteriorate and those who do not respond prednisolone, which has greater potency. This is typicaly given in adose of
after 7-10 days' maximal medical treatment usualy require urgent sur 40mg daily, reducing by 5mg/week over &weeks, at which point treatnert
gery. Subtotal colectomy with end ileostomy is the operation of choice is stopped. Oral prednisolone inthe dose regimen descrbed above is the
and can be performed open or laparoscopically, dependent upon local treatment of choice for inducing remission in colonic Crohn's disease.
expertise. The surgical and medical teams should liaise early in the dis As an alternative to glucocorticoid therapy, enteral nutrition with ether
ease course and, if possible, the patient should have the opportunity to an elemental (constituent amino acids) or polymeric (liquid protein) det
speak with the stoma nurse prior to colectomy. may induce remission. Both types of diet are equally effective, but the
polymeric one is more palatable when taken by mouth, and this improves
Maintenance of remission adherence. It is particularly effective in children, in whom equal eficacy to
Life-long maintenance therapy is recommended for all patients glucocorticoids has been demonstrated. and in extensive leal disease n
with left-sided or extensive disease, but is not necessary in those adults. As well as resting the qut and providing excellent nutrtiona su
with proctitis (although 20% of these patients wil develop proximal port, it also has a direct anti-inflammatorv effect, It is an effective broge
and can be gven oy
'extension' over the lifetime of their disease). Once-daily oral 5-ami T0 Urgent staging investigations at first presentation encouay
nosalicylates are the preferred first-line agents. Sulfasalazine has a mouth or by nasogastric tube, With sufficient explanation,
higher incidence of side-effects, but is equally effective and can be ment and motivation, most patients willtolerate it well.
considered in patients with coexistent arthropathy. Patients who fre
quently relapse despite aminosalicylate drugs have in the past always Induction of remission in severe disease glucocort
been offered thiopurines (azathioprine or 6-mercaptopurine). While systemic
Patients with severe disease can be treated with considered, pro
thiopurines still have an important role for treatment, other immuno be
coids. The early introduction of biologics can alsoas abscess. havenot
Suppressive drugs may also be used. Biologic therapy with anti-TNF viding that acute perforating complications, Such integrin (ved
antibodies (infliximab, adalimumab or golimumab) can be consid anti-a4ß7
ered for maintenance treatment in patients with moderate to severe arisen. Anti-TNF (infliximab or adalimumab), can be consideredas
olizumab) and anti-p40 (ustekinumab) therapy disease
ulcerative colitis. Combination therapy of infliximab persistentlyactive
with a thiopurine first-line biologics. Patients with evidence of
should be used, as it is more effective than
monotherapy
mab. patients where anti-TNF treatment has failed,
In with inflixi require further maintenance treatment (see beloW).
grin antibodies (vedolizumab), Janus kinase anti-a4p7 inte
inhibitors (tofacitinib) and Maintenance therapy Crohnsds
in
anti-p40 antibodies (ustekinumab), can be considered to remission
azathioorine
and
remíssion. maintain Glucocorticoids are rnot effective at maintaining
treatment with thiopurines
ease. Immunosuppressive
 Inflammatory bowel dis

370-How to give anti-tumou DeCrosis factor (TNF therapy in

inflanmatory bowel disease' 23.71 Indications for surgery in ulcerative colitis
V nfuSioni is given as three ioadina dosSes (at 0,2 and E
nfnnab(5 mag ko Impaired quality of life
" Weeisi, wth 8.-weekty maintenancethereafter. Some patients may require dose
4 weekty Loss of occupation or education
esralatn to 10mg kg up to trained to gye
nmab is ghen as SC Injections, which patrents can be " Disruption of family life
ma 2 weeks ater and
omsehes Loading ose is 160mg. followed by 80 Failure of medical therapy
second week thereafter. some patients require dose escalation to
mg eVey
40 " Dependence on oral glucocorticoids
40mg onoe weeky
" Resistant to drug therapy
Concomitant immunoSuppression with thiopunne or methotrexate may be
a
" but has more side-effects " Intolerable side-effects of drug therapy
more effcacious than monotherapy infection and
[Link] theraoy is contraindicated in the presence of active Fulminant colitis
ubercuiosis without appropriate prophylaxis; it carnes an increased risk
atent " Life-threatening bleeding
oonortunistc infections and a possible increased risk of malignancy: rarely.
of
m°ltipie scierosis may be unmasked in suSceptible individuals. Counselling Toxic megacolon
for each patient is im0ortant
abaut the balance of isk and benefitmust . Perforation
therapy, latent tubercuosis be e excluded, as well as checking
Prior to Colon cancer or severe dysplasia
immunisation status, as wel as hepatitis B, hepatitis C, HIV and VZV status
shouid not be gven
. Live accines colitis
Goimumab is effective for ulcerative
Cartlumab is effective for luminal Crohn's disease, but is not licensed in
Europe
Surgical management
Ulcerative colitis
UN-hman immunodehciency vrus, V =Intavenous, SG= subcutabeous: TNF = fumour
zoster virus)
nacrosis factor; VZV= vanicella Up to 60% of patients with extensive ulcerative colitis eventually require
surgery. The indications are listed in Box 23.71. Impaired quality of life,
with its impact on occupation and social and family life, is the most
important of these. Surgery involves removal of the entire colon and rec
tum, and cures the patient. One-third of those with pancolitis undergo
mercaptopurine) may be Used as maintenance therapy, but methotrexate colectomy within 5 years of diagnosis. Before surgery, patients should
is also effective and can be given once weekly, either orally or by subcu be counselled by doctors, stoma nurses and patients who have under
taneous injection; subcutaneous administration has better bioavailabiity gone similar surgery. The procedure of choice is usually an initial subtotal
Patients refractory to immunomodulator therapy should be considered colectomy with ileostomy and a subsequent ileorectalanastomosis, or a
for biologic therapy with anti-TNF (infliximab or adalimumab) (Box 23.70). proctocolectomy and ileal pouch-anal anastomosis. The Companion text
anti-a4B7 integrin (vedolizumab) or anti-p40 (ustekinumab) therapies). to this book, Principles and Practice of Surgery, should be consulted for
Combination therapy of infliximab with a thiopurine should be used, as further details.
it is more effective than monotherapy with infliximab. Combination ther
Crohn's disease
any of infiximab with methotrexate may also be used to reduce immu
nogenicity. In patients who still require glucocorticoids despite optimal Operations are often necessary to deal with fistulae, abscesses and per
treatrment with biologics, other options must be considered including ianal disease, and may also be required to relieve small or large bowel
surgery. obstruction. In contrast to ulcerative colitis, surgery is not curative and
Cigarette smokers with Crohn's disease should be strongly coun disease recurrence is the rule. The only method that has consistently
selled to stop smoking at every possíble opportunity. Those that do been shown to reduce post-operative recurrence is smoking cessa
not manage to stop smoking fare much worse, with increased rates tion. Antibiotics are effective in the short term only. Use of thiopurines
of relapse and surgical intervention, with adverse effects of smoking post surgery is suggested if there are indicators of a high chance of 23
being more pronounced in women than in men. Careful monitoring recurrence, i.e. more than one resection or evidence of penetrating dis
of disease activity (see Box 23.69) is the key to maintaining sus ease, such as fistulae or abscess. Otherwisse, it is common to undertake
tained remission and preventíng the accumulation of bowel damage colonoscopy 6 months after surgery to inspect and biopsy the anas
in Crohn's disease. tomosis and neo-terminal ileum. Patients with endoscopic recurrence
are then prescribed immunomodulators or biologics to prevent further
Fistulae and perianal disease complications.
Fistulae may develop in relation to active Crohn's disease and are Surgery should be as conservative as possible in order to minimise
often associated with sepsis. The first step is to define the site by the loss of viable intestine and to avoid the creation of a short bowel
imaging (usually MRI of the pelvis). Endoanal ultrasound is another syndrome (p. 771). Obstructing or fistulating small bowel disease may
option for assessment, but is limited in patients with luminal stenoses, require resection of affected tissue. Patients who have localised seg
as well as by local expertíse. Surgical exploration by examination ments of Crohn's colitis may be managedby segmental resection and/
er anaesthetic is usually then required, to delineate the anatomy or multiple stricturoplasties, in which the stricture is not resected but
and drain abscesses. Seton sutures can be inserted through fistula instead incised in its longitudinal axis and sutured transversely. Others
wavts to ensure adequate drainage and to prevent future sepsis. who have extensive colitis require total colectomy but ileal pouch for
diuCocorticoids are ineffective. UJse of antibiotics, such as metroni mationshould be avoided because of the high risk of recurrence within
dazole and/or ciprofloxacin, can aid healing as an adjunctive treat- the pouch and subsequent fistulae, abscess formation and pouch
oL. Ihiopurines can be used in chronic disease, but do not failure.
usually
vouil in tistula healing. Anti TNF therapv can heal fistulae and peri Historical datasets show that around 80% of Crohn's patients
anal
disease in many patients and are indicated when the measures undergo surgery at some stage and 70% of these require more than
described above have been ineffective. Higher trough infliximab drug
are aimed for in
one operation during their lifetime. Clinical recurrence following resec
efit in perianal Crohn's disease. The evidence of ben tional surgery is present in 50% of all cases at 10 years. Emerging
perianal
unclear. Other fistulating
Or laecal
diseasefor the newer biologics is presently
options for refractory perianal disease are proctectomy
data demonstrate that aggressive medical therapy, coupled with
intense monitoring, probably reduces the requirement for surgery
diversion with an upstream stoma. substantially.
 846 " GASTROENTEROLOGY

2372 Infammatory bowel disease in

IBD in special circumstances adolescence
Delayed growth and pubertal development:
Childhood than adults. malabsorption,malnutrition and long-term chronic actsive
Children developing IBD tend to
have more extensive disease impaired
or adolescence may result in development, with physical and Continrfilbautmmat
short stature and delayed glucocorticoids
e toion
chronic psychological
Chronic ill health in childhood
Consequences.
puberty. Loss of schooling
delaved
and Metabolic bone disease: more common with
groth, metabolic bone disease impor
freguent hospitalisation, can have
and social contact, as well as that described
from
in childhood, resulting chronic
inflammation, dietarydisease beginniandng
tant psychosocial
conseguences. Treatment
invove glucocorticoids,
is similar to
immunosuppressive drugs,
malabsorption of calcium and vitamín D
Drug side-effects and adherence 0ssues: young people deficiency
for aduts and may
However, exclusive enteral
nutrition can also require azathioprine or biologic therapy than adults. are more to
biologic agents and [Link] in Crohn's disease, as well as aid adults, younger patientsPoor likely
self-motivation to adhere and believe that drugs are mayadher
[Link]
is more common than with as
disease
be used to induce height, weight and
growth and nutntional status. Monitoring of ineeffective or cause side
ing with with IBD should be managed by effects.
orucial. Children
sexual development is gastroenterologists Loss of time from education: physical
and transitioned to adult care illness, surgery, fatique in
inflammatory bowel disease, privacy and dignity issues.
specialised paediatnc
23.72). allcontribute. and social chronic,
in dedicated clinics (Box
Emotional difficulties: may result from challenges in isolation may
problems with forming interpersonal Irelationships, and icoping with illness.
Pregnancy
managed in an MDT approach involv image or sexual function. isSues relating to body
Pregnant women with IBDare best
obstetrician. A Woman's ability to become
ing an BD physician and an counselling
affected by active IBD. Pre-conceptual
pregnant is adversely
During pregnancy, roughly
should focus on optimising disease control. and one-third remain
23.73 Pregnancy and intiammatory bowel disease 1BD
get worse
one-third of women improve, one-third
post-partum period, these changes
stable with active disease. In the pregnancy
Pre-conception
spontaneously, e.g. improvement during
sometimes reverse aminosalicy
e Outcomes are best when pregnancy Is careruly planned and disease in i
including
is followed by post-partum relapse. Drug therapy,can be safely continued remission
lates, glucocorticoids, thiopurines and biologics " Methotrexate must be stopped 6 months prior to conception; other
throughout pregnancy, but methotrexate and tofacitinib
must be avoided, should be continued until discussed with a specialist 1BD drugs
23.73). Biologics such
both duning pregnancy and pre-conception (Box " Aminosalicylates and azathioprine are safe in pregnancy
as inflbximab, adalimumab, vedolizumab and
ustekinumab may pass " Glucocorticoids are probably safe
and concentrate in the fetus, especially in the last " Biologic therapy (infliximab, adalimumab, vedolizumab, ustekinumab) in
across the placenta
choose pregnancy can continue if established pre-pregnancy
trimester. Some wormen who are in deep remission may therefore " Tofacitinib should be avoided in pregnancy
biologics can be
to omit their biologics in the last trimester. However, " Folic acid (5 mg/day) is recommended pre-conception. Consider high-dnse
safely continued throughout the pregnancy, especially in women with
limited treatment supplements in smallbOwel Crohn's disease with low levels despite 5mg dose
ongoing active disease, at high risk of relapse or when
options. Breast feeding is recommended in all women and the use of Pregnancy
not preclude women from breastfeeding. " TWo-thirds of patients in remission will remain so in pregnancy
thiopurines and biologics does
Thiopurine drug levels in breast milk are very low, with negligible levels " Active isease is likely to remain active
measured in breast-fed infants of mothers on thiopurines. Levels of bio " Severe active disease carries an increased risk of premature delivery and Iow
iogics are also very low in breastmilk and lead to negligible levels in the birth weight
breast-fed infant due to normal gut digestion. Mode of delivery should be " Perform endoscopy only when absolutely essential for clinical decision-making
discussed with pregnant women and in the absence of active rectal or (ideally in second trimester)
X-rays can be performed if clinically indicated, but discuss with the radiologist
perianal fistulatingdisease, where a caesarean section is recommended,
a vaginal delivery is safe.
first. Ultrasound is preferable but is operator-dependent. MRl small bowel can
be performed without intravenous gadolinium and oral contrast
Labour
Metabolic bone disease
" This needs careful discussion between patient, gastroenteralogist and
Patients with IBD are prone to developing osteoporosis due to the efects obstetrician
of chronic inflammation, glucocoricoids, weight loss, malnutrition and Normal labour and vaginal delivery are possible for most
malabsorption. Osteomalacia can also occur in Crohn's disease that is " Caesarean section may be preferred for patients with perianal Crohn s or al
conplicated by malabsorption, but is less common than osteoporosis. leo-anal pouch to reduce risks of pelvic floor damage, fistulation and late
The risk of osteoporosis increases wvith age and with the dose and dura incontinence
tion of glucocorticoid therapy. Patients should have their fracture risk " Venous thromboembolism prophvlaxis is important if in hospital
assessed prior to glucocorticoid therapy. Individuals who receive pro Breastfeeding
ionged (> 3months) or repeated courses of oral glucocortocid therapy " This is safe and does not exacerbate IBD mOSt
should have bone densitometry assessed. Oral bisphosphonates, in the arelimited:
Data on the risk to babies from drugs excreted in breast milk
form of alendronate and risedronate, are Commonly used for treatment
if required. DenoSumab and high dose intravenous bisphosphonates of these drugs are probably safe
should be avoided in women of childbearing age, due to their unknown " Patients should discuss breastfeeding and drug therapy wiui Uieu e
effects on the fetus.
recommended
t is therefore ileumshoua
Microscopic colitis biopsies shows a range of abnormnalities, terminal
the aliarrhoea. An
that biopsies of the right and left colon pluS
colonosCopyfor lymphocytess
Microscopic colitis, which comprises two related conditions called lym be undertaken in all patients undergoing
phocytic colitis and collagenous colitis, has no known cause. Both forms lamina propria subepthe
are commoner in women witha mean age of increased number of intraepithelial and with athickened Microscopiccolt'S
presentation of around 60 noted in both forms of microscopic colitis, dsease.
years. The presentation is with chronic non-bloody watery diarrhoea. The collagenous colitis. coeliac
lial collagen band also noted in as
colonoscopic appearances are normal, but histological examination of diseases such
may be associated with autoimmune
rheumatod athritis andthyroid disease. and some drug
as NSAIDs and
PPls. Bile acid therapies, Such
diarrhoea has also been reported to be
inthis group. Treatment with budesonide is
uSually
for inducing remiSSIOn. Up to rO% Of individuals can relapseeffec-
and
requre further treatment. but others can remain symptom free.

Gunctional bowel disorders