Refer under 16s to Paed gastro. Patients prefer cf adult services!

Microbiome pivotal to development of IBD (among other things, eg allergy).  Plus genetic factors – first degree relatives of Crohn’s patients have up to 35x greater risk!  When risk assessed on basis of genotype and smoking, 32% of apparently asymptomatic had evidence of small bowel inflammation (and quite a few had moderate-severe inflammation).

In this study calprotectin over 150microg/g was 95% specific for inflammation (32.6% sensitive). [Poster 2016]

Higher calprotectin in relatives correlates with dysbiosis (ie lower microbial diversity and shifts in composition, including more enterobacteriaceae). [Cell Molec Gastroenterol Hepatol. 2016 Jul 4. doi: 10.1016/j.jcmgh.2016.06.004]

Pathology is leaky tight junctions, innate and adaptive immunity defects.

Types:

• Crohns  – transmural, skip lesions, mouth to anus.  70% have granulomas.
• Ulcerative colitis – always involves anorectal region, continuous, more superificial
• IBDU (undifferentiated)- mucosal only, colon only (cf rectal in UC).  Some evolve into more typical Crohns or UC.

Still rising incidence of Crohns in Scotland (5x in 34 years)!

Presentation

Abdominal pain, diarrhoea (esp bloody), weight loss.  Nocturnal stooling.

Small bowel IBD can present like anorexia nervosa!

Acute/chronic “appendicitis” = terminal ileum Crohns.

Drop in height centile can precede gut symptoms.

Clinical Features

• Cobblestoning of oral mucosa, buccal tags
• Swollen joints,
• Erythema nodosum,
• Anal fissures or tags.
• Growth parameters.
• Ileocaecal mass.
• Pyoderma gangrenosum is a rare association.

Investigations

Calprotectin is a neutrophil protein.  False pos in infection, polyps, under 5s.  Reduces endoscopy rate by 35%, and earlier diagnosis for some.

200-250 is starting to get specific.  Don’t do under 5yrs!

MR better detail, less radiation for small bowel.  But low availability and expertise.

Treatment

2016 BSPGHAN ArchDisChild guidelines. 

Emphasis on mucosal healing, not just symptoms eg bloods, calprotectin, imaging.

Crohn’s disease

Exclusive nutritional mx 6-8/52 is preferred for active luminal Crohns, mucosal healing better cf steroids.  Microbiome changes, but not to normal!

Solid food version of Modulen being developed.

Early Azathioprine for maintenance.  (Mercaptopurine more appropriate for young children).  Check TPMT enzyme activity to avoid toxicity, start full dose rather than titrating up (2mg/kg unless enzyme pos).  Check metabolite levels if poor response or side effects. Using “discordant metabolites” (6TG, 6MP) benefit from split dosing.

MTX for failed aza (preferred if arthritis).

Surgery good for local disease – no need to fail medical!

Weighted paed CD activity index (wPCDAI) – app available!  PUCAI app not strictly legal…

Anti-TNF treatment – occ non-responders, check levels first!  First line in US, similar to rheumatology: use best Rx first!  Biosimilars available now, cheaper but more complex to make so higher risk of reactions?  Prescribe by brand name.  So far no concerns.

VEDOLIZUMAB – vs gut-tropic lymphocyte migration.  Approved in adults.

20% Crohns don’t get change in bloods with acute exacerbations!  Check stool cultures and C diff, can start EEN pending results.

See Ulcerative Colitis.

Prognosis

Mean final height in CD 2.4cm below target.

Transition only when completed growth and development and without education/psych issues.

SSPGHAN guidelines 2014

About a third of IBD in kids, incidence stable unlike Crohn’s.

Associated with autoimmune disease especially sclerosing cholangitis.
80% kids have pancolitis (cf 20% adults), otherwise proctitis alone or
other local disease.

Acute Severe Colitis

“About saving lives, not saving colons”.

15% severe at presentation, 28% have at some point in childhood.

The first attack of colitis tends to be more severe and disease more
extensive in children than in adults. Many respond to conventional
medical therapy but 8-30% at 1 year will have undergone colectomy for
failed medical treatment (depending on disease severity).

Acute severe colitis is characterised by greater than 6 bloody stools
per day, abdominal tenderness, fever, anaemia, leucocytosis, and
hypoalbuminaemia. This is a typical presentation of ulcerative colitis
or may occur as an exacerbation, but the differential includes:

• Infectious colitis eg Shigella, E. coli O157
• Crohn’s colitis
• pseudomembranous colitis
• ischaemic colitis

Equivalent to PUCAI >65. Moderate colitis 35-60.  Day 3 PUCAI already predictive of future colectomy, second line therapy.

Clostridioides prev Clostridium difficile- less in kids than adults.  Intermittent shedding so multiple samples required.

CMV colitis – not always immunosuppressed.  But no evidence for treatment or prophylaxis…

1-1.5mg/kg max 60mg IVMP.  If toxic or colonic dilatation then NBM, antibiotics, surgical opinion.

Day 3 under 35 PUCAI can consider oral steroids (120% IV dose).  Over 45 refer tertiary centre, screen for second line therapy, start involving surgeons/stoma therapist, sigmoidoscopy (safer than full colonscopy), check HBV/HCV/TB for starting ANti TNF Rx.

Day 5 over 65 start second line (infliximab).  “Sponge, sieve, shark”.  Dose, timing?  Sponge soaks up Abs.  Shark is immune system removing Ab.  Sieve – leaking Ab?  Not much evidence yet!

No response at day 11 consider colectomy.

Alternative second Rx are ciclosporin, tacrolimus.

Toxic megacolon – pain, distension.  Signs less if already on steroids.  Amp, gent, metro.  40mm under 10, 56mm otherwise.

Thrombosis – recognized risk of stroke.  Consider 3+/12 treatment prophylaxis eg OCP, FH

No evidence for bowel rest!

Number of stools can be over estimated if very close episodes. Some may conceal or underestimate number/blood.

Investigations

• FBC, coag
• Group and save – consider Cross match esp if possibly for surgery
• CRP, ESR
• U&Es, LFTs, Ca – hypokalaemia can precipitate toxic megacolon
• Blood culture, stool cultures, stool microscopy, C diff toxin
• CMV serology if immunocompromised
• AXR – toxic megacolon = 5.5cm+ dilatation

These also used for monitoring, in addition to PUCAI score, a clinical score:

• abdominal pain (can be ignored or not),
• rectal bleeding (some stools, most stools, more blood than stool),
• stool consistency and frequency,
• nocturnal stooling,
• activity level (limitation or not).

Under 10 normal, 10-30 mild, 30-60 moderate.  Best averaged over 2 days unless rapidly changing clinically.

Endoscopy is not considered first line investigation given risk of
performation. Limited sigmoidoscopy may give useful information
however.

Management

• Fluids and nutrition
• Blood transfusion, esp if Hb<8 or <10 and symptomatic
• Consider antibiotics (IV Cef and met) if high risk of infection or pre-surgery
• Stop aminosalicylates until improving
• Steroids – Hydrocortisone 10mg/kg in 4 divided doses, max 400mg/d else Methylprednisolone 1mg/kg, max 60mg. Do not delay pending microbiology!
• TED stockings, LMWH
• Surgical review

Joint medical/surgical care is appropriate. If surgery is likely to be
needed, a stoma nurse would be useful. PUCAI >45 on day 3 suggests
failure to respond (30-70%, depending on severity). Cyclosporin and
Infliximab are second line.

Maintenance

Azathioprine and 6MP are useful for maintenance, less useful acutely
given delayed onset of action. TPMT deficiency predicts myelotoxicity
(use lower doses). 6MP has less side effects (nausea, vomiting,
headache, fatigue). prob best for younger kids.

Sulphasal liquid, various granule products for older kids.

Mesalazine enemas good but low acceptability.

[Richard Hansen 2016]