Gastroenterology Today Summer 2021


Gastroenterology Today Summer 2021

Volume 31 No. 2

Summer 2021

Gastroenterology Today

What approach has 18 Week Support

taken with regards to building an

expert insourcing team?

Matthew’s Perspective:

Dr Matthew Banks is the Clinical Director for 18 Week Support Gastroenterology. He believes it starts with recruiting the

best clinicians. ‘At 18 Week Support we set the bar very high. We only recruit clinicians whose JAG performance data is well

above the national standards. In addition, we monitor each clinician’s KPIs while they work with 18 WS. While the JAG data

is an excellent quality indicator, we now want to go a step beyond that and monitor the Non-Technical skills (NTS) of each

clinician as well. We now know that NTS plays an important role in safe and effective team performance. Therefore, in our

quest to develop excellent teams who deliver a world-class service, we must focus on NTS’.

Tammy and Lisa’s Perspective:

Tammy Kingstree is Lead Nurse for Endoscopy.

‘It is extremely important that there are good working relationships within the team. This starts with strong leadership from

our senior nurse coordinators who are trained to manage the patient pathway, manage a team of staff they may not know

and to deal effectively with any issues which may arise on the day’.

Lisa Phillips is Lead Nurse for Endoscopy.

‘The team objectives are clear. Excellent patient experience and good patient outcomes. Because the objectives are clear,

team cohesion and focus are exceptionally good. It therefore shouldn’t matter that we are in an unfamiliar endoscopy unit,

the service should be seamless. If it isn’t, we do not stop until we get it right.

If you have an excellent NHS record and want to help clear NHS waiting list backlogs, reduce RTT waiting times and provide

18 Week Support Gastroenterology:

Partnering to Succeed

high-quality patient care, get in touch by calling on 020 3892 6162 or email

Dr Matthew Banks

Clinical Lead for Gastroenterology


Find out more at

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Gastroenterology Today


6 FEATURE Encouraging Uptake of Faecal Immunochemical

Tests (FIT) in Assessment of Patients with

Lower Bowel Symptoms

12 FEATURE Diagnosis and management of coeliac disease

in specialist paediatric gastroenterology centres

in the UK

14 FEATURE The incidence and prevalence of inflammatory

Matthew’s Perspective:

bowel disease in UK primary care: a

retrospective cohort study of the IQVIA Medical

Research Database

20 CASE REPORT Heavy metal in the gastroenterology clinic

22 CASE REPORT Infliximab-induced seizures in a patient

with Crohn’s disease: a case report



This issue edited by:

Hesam Ahmadi Nooredinvand

c/o Media Publishing Company



Upper Sapey, Worcester, WR6 6XR

What approach has 18 Week Support

taken with regards to building an

expert insourcing team?


Media Publishing Company

Greenoaks, Lockhill

Upper Sapey, Worcester, WR6 6XR

Tel: 01886 853715


Dr Matthew Banks is the Clinical Director for 18 Week Support Gastroenterology. PUBLISHING He believes it starts DATES: with recruiting the

best clinicians. ‘At 18 Week Support we set the bar very high. We only recruit March, clinicians June, whose JAG September performance data and is well December.

above the national standards. In addition, we monitor each clinician’s KPIs while they work with 18 WS. While the JAG data

is an excellent quality indicator, we now want to go a step beyond that and monitor the Non-Technical skills (NTS) of each


clinician as well. We now know that NTS plays an important role in safe and effective team performance. Therefore, in our

quest to develop excellent teams who deliver a world-class service, we must Media focus on Publishing NTS’. Company


Tammy and Lisa’s Perspective:


Tammy Kingstree is Lead Nurse for Endoscopy.

‘It is extremely important that there are good working relationships within Upper the team. Sapey, This starts with Worcester, strong leadership WR6 from 6XR

our senior nurse coordinators who are trained to manage the patient pathway, manage a team of staff they may not know

and to deal effectively with any issues which may arise on the day’.

Lisa Phillips is Lead Nurse for Endoscopy.


The views and opinions expressed in

this issue are not necessarily those of

the Publisher, the Editors or Media

Publishing Company.

‘The team objectives are clear. Excellent patient experience and good patient outcomes. Because the objectives are clear,

team cohesion and focus are exceptionally good. It therefore shouldn’t matter that we are in an unfamiliar endoscopy unit,

the service should be seamless. If it isn’t, we do not stop until we get it right.

If you have an excellent NHS record and want to help clear NHS waiting list backlogs, reduce RTT waiting times and provide

high-quality patient care, get in touch by calling on 020 3892 6162 or email Next

Issue Autumn 2021


In this edition we explore developments in CPD and education, in particular

how digital learning is contributing to the further development of technical

skills, diagnosis and disease management in endoscopy, all of which are vital

to quality, safety and efficiency.

Our JAG quality standards generally exceed the UK average (National

Endoscopy Database) but obviously no health organisation can afford to rest

on its’ laurels when it comes to quality and safety. This is why we have recently

partnered with GastroLearning, an endoscopic educational platform pioneered

by University College London consultants that delivers high-quality CPD and

educational content digitally.

All practitioners registered with 18 Week Support can access GastroLearning’s

education channels and content free of charge. In this post-pandemic world

the provision of education is changing fast. Formal conferences will continue

to have their place, but medical practitioners are increasingly switching to

content delivered across multiple digital channels that is directly relevant to

their need and which can be accessed at a time which best suits their busy

working lives. Read the article to see more about the content provided and

how it delivered free to any practitioner joining us here at 18 Week Support.

Subscription Information – Summer 2021

Gastroenterology Today is a quarterly

publication currently sent free of charge to

all senior qualified Gastroenterologists in

the United Kingdom. It is also available

by subscription to other interested individuals

and institutions.


Other medical staff - £18.00 inc. postage

Non-medical Individuals - £24.00 inc. postage



Commercial Organisations - £48.00 inc. postage

Rest of the World:

Individuals - £48.00 inc. postage



Commercial Organisations - £72.00 inc. postage

We are also able to process your

subscriptions via most major credit

cards. Please ask for details.

Cheques should be made


Designed in the UK by me&you creative









changed our

practice. One

such change

has been a

shift toward



which is, at

least in part,

here to stay.”

The incredible success of the COVID 19 vaccination has given us all hope. Although

most would agree this virus, like almost all others, will likely never be fully eradicated,

the success of the vaccination programme has meant a greater degree of freedom as we

gradually exit from lockdown. COVID 19 has not only affected the lives of our patients’

both physical and psychological wellbeing over the past sixteen months but the collateral

damage it has inflicted will likely be experienced for years to come. The measure of

the true impact of this is yet to be fully appreciated but given the reduction in access

to healthcare, it is inevitable that the delay in diagnosis and treatment is resulting in

increased morbidity and mortality for many patients particularly the elderly and those with

chronic conditions.

The pandemic has dramatically changed our practice. One such change has been a

shift toward remote consultations which is, at least in part, here to stay. This does not

only have the potential to improve the financial efficiency of our services but also many

patients prefer this to face to face consultation given the cost and inconvenience of travel.

Its success will however depend on being able to identify the group of patients for whom

remote consultation is appropriate and optimal as well as addressing digital literacy issues

particularly in the elderly.

Hesam Ahmadi Nooredinvand,

St George’s Hospital




We’ve made

Gastroenterology a true

7 day NHS service

Join forces with the UK’s largest campaign to see and

treat those NHS patients who need you most. All working

as part of an expert clinical team in outpatient clinics or

undertaking Endoscopy procedures, getting the right care

to those patiently waiting.

Register your support or enquire below.

Together, we can end the wait.





Keywords: Faecal immunochemical test (FIT), COVID-19, bespoke, FIT-KIT, triaging, endoscopy, waiting time.




In April 2020, all non-urgent endoscopy procedures were

suspended due to the COVID-19 pandemic. Consequently,

those referred for colorectal cancer (CRC) investigation in

England under the NG12 1 and DG30 2 guidelines faced increasing

waiting times. It became necessary to triage these patients to

allocate resources effectively. However, the pandemic makes

patient contact challenging, reducing the number of face-toface

consultations to minimise the spread of COVID-19. Faecal

immunochemical tests (FIT) offer a unique solution since the

process can be managed “contact free”, reducing risk to patients

and health workers. Faecal sample collection by patients is still

novel, compared to other sample collection methods such as

for blood tests. However, patients are often reluctant to handle

faecal samples. A solution must, therefore, have a patient-centred

approach to encourage sample collection and return, while

ensuring good quality samples for analysis. The answer lies

in the provision of bespoke patient literature. Trust and Health

Board specific leaflets with local phone numbers, QR-codes,

barcodes, and clear visuals, with non-clinical instructional text,

provide much needed support to FIT pathways which, in turn, has

aided the management of endoscopy waiting lists. The bespoke

leaflets result in noticeable increases in return rates, and the

quality of samples received by laboratories are also much


The onset of the COVID-19 pandemic caused widespread disruption to

many clinical diagnostic pathways. Already overburdened endoscopy

services faced considerable reductions, resulting in fewer procedures

and, in consequence, fewer diagnoses of colorectal cancer (CRC) and

other significant bowel diseases. CRC is highly treatable if detected in

its early stages 3 and long-term quality of life is much improved following

successful treatment. However, the waiting times for endoscopy have

resulted, and still are resulting, in concerning delays to diagnosis 4 .

Therefore, a supporting pathway is a necessary prerequisite to alleviate

pressure on the service and prioritise those with the most severe

symptoms for further investigation.

Use of FIT

It is widely appreciated that FIT is the ideal tool to use, not only to

continue supporting the existing primary care pathways, as guided by

NICE NG12 1 and DG30, 2 but also for use in secondary care and triaging

patients on waiting lists. National guidelines published in both England 5

and Scotland 6 outline how FIT can be used to support CRC referrals in

the pandemic, by using higher faecal haemoglobin concentration (f-Hb)

thresholds than that recommended originally for the low-risk cohort

under DG30. 2

The f-Hb is proportional to the risk of severe disease and has been

proven to be a valuable marker even in those referred with rectal

bleeding 7 , suggesting that FIT is suitable in both high- and low-risk

patient groups. This is further supported by recent diagnostic accuracy

studies, highlighting that the negative predictive value (NPV) for CRC

is over 98.9% 8 even when using a high threshold of 150 µg Hb/g

faeces. Other possible thresholds for investigation have been very

recently documented in detail 9 . However, ubiquitous use of FIT in the

triage for further investigation of patients presenting with symptoms

is still relatively novel in terms of sample collection and logistics, so,

while technically FIT is a suitable test, its application must be carefully

managed to ensure the issues with overburdened services are resolved,

and not just relocated.

Managing Remote Sample Collection

GP consultations dropped by 30% between the end of March and end

of May 2020 10 , and primary care is the most common starting point

for referral for patients with suspected CRC. With this decrease, there

was concern surrounding the use of FIT and how well clinical pathways

could be supported. To address this, innovative logistics strategies

were required because good engagement is a key driver to motivating

patients to collect and sample faeces and return these samples for

analysis. Since telephone and video consultations increased sharply, it

was considered that the FIT sample collection device and instructions

for use, could be posted out to the patient, as well as being collectable

at the GP surgery. After the sample is collected by the patient, the

device is either posted back to the laboratory or dropped off at the GP

surgery for onward transport. These approaches make the complete

process between consultation and the generation of a result “contact

free” and therefore considerably reduces the risk of spreading

COVID-19. With the sample collection, handling, transport, and

other logistics now in place, encouraging correct use is clearly a vital


Maximising Uptake

With such reliance on samples collected by patients, uptake is vital. With

faecal samples, there are the associated “fear” and “disgust” factors

which deter some patients from collecting the sample, in spite of the


simple, easy to use, hygienic FIT sample collection devices. However,

bespoke instruction for use (IFU) leaflets have been hugely influential in

increasing uptake and improving sample quality. Such IFU are based

around core sampling requirements but adapted to suit the specific

clinical pathway adopted by Trusts and Health Boards. With local

contact numbers, bar-codes, and detailed pathway information, patients

are made to feel included in the diagnostic process and are provided

with the tools to complete the sample collection successfully or talk to a

knowledgeable professional should they have any questions. IFU have

evolved over time, after initially being used in primary care, FIT is now

being used in a more diverse range of patients, 11 so the detail must be

regularly reviewed to ensure suitability. Usability studies, consultation

events, focus groups and feedback from cancer charities all could

contribute to the design and production of these IFU to maximise the

inclusivity of the process.

The design and application of sample collection devices are suited

to patient-based sampling and, although the attributes will not be

discussed in detail here, research has been conducted on the efficacy

of FIT in the hands of patients, 12,13 , proving them suitable for this

application. Additionally, the IFU provide supporting information such

as tips for collecting the faeces prior to using the device, which helps

familiarise using faeces as a sample and helps break some of the

barriers to the sampling process. It also helps reduce contamination risk

in terms of the faecal sample, and the sample collection device.

FIT for All

The last, and possibly most critical, barrier to uptake, is ensuring the IFU

are suitable for a range of patient groups. With FIT now being used in a

diverse range of patients, the bespoke literature must be as inclusive as

possible, ensuring patients can understand and follow the instructions.

As discussed above, the use of simple colourful pictures or diagrams

and text help those with visual impairments, or those for whom English

is not a primary language, and the additional information provided, such

as phone numbers, links to videos and websites, provide more routes

for patients to access help should this be required. It is important to

consider that a FIT device should not be simply handed to a patient with

no advice: as part of the safety-netting process, FIT should be provided

following a discussion with the patient.

Large, full-colour pictures with accompanying text provide patients

with user-friendly guidelines on the collection of faeces, using the

sample collection device to take the sample, and then how to return it

for analysis. Additional information should be provided on the clinical

pathway, why the test has been requested, and who to contact if

the patient has questions. These personalised aspects reduce the

unpleasantness associated with faecal sample collection. Their

introduction has resulted in an increase in return rate facilitating a

service to maximise impact and alleviate some waiting times.

Quality Samples

Any pathway involving a patient collected sample must yield samples

suitable for analysis. With FIT, there has been much scrutiny over the

use of a patient utilised sample collection device and the possible

impact on the laboratory result and, therefore, on patient outcome. The

primary consideration here is that FIT should never be used in isolation

and should be a tool applied in conjunction with clinical suspicion

and adjunct tests including the full blood count and iron studies when

appropriate, to further reduce the risk of missing CRC, particularly in

complex patients on waiting lists. 11

Concerns around patient sampling include over-sampling, undersampling

(or even, not sampling at all and providing an unused device

for testing). Contaminating the faeces prior to sampling with, for

example, menstrual blood and toilet cleaners can also be an issue.

To ensure continued relevance in the pathway, IFU are continuously

reviewed. Involvement with patients, key opinion leaders, and

feedback from laboratories all contribute to the ongoing improvement

programmes. Ensuring fidelity to the Trust or Health Board’s specific

clinical pathway helps the laboratories manage the samples effectively,

reducing the risk of overburdening the analytical capability. Feedback

is positive, with many reports showing over 90% of patients have been

able to follow the IFU and use the device as intended. 14


The initiation of the use of FIT following the design of an IFU includes

the logistics: some encourage the GP surgery to hold stock of the

FIT-KITs (device, plus IFU, plus return envelope) so distribution is

managed on a local level, whereas others (particularly those with

electronic test requesting) have a centralised location from which the

FIT-KITs are distributed. Both models work for their respective users,

with stock management and logistics managed in a similar way to other

consumables, slotting into already proven processes.

Sample return logistics are also well studied. Originally, postal

return services, similar to the methods used in the bowel screening

programmes conducted in all four nations of the UK, was preferred,

reducing the footfall in GP surgeries, and giving patients a quick and

convenient sample return method. The ambient temperature stability

of any haemoglobin present after collection of faeces means a postal

return service would be a suitable route for sample returns. However,

due to cost implications, the return of samples via the GP surgery is

becoming more popular, negating the postage costs. Samples can be

efficiently and effectively returned to the laboratory with other types of

specimens via existing transport services. There has been no reduction




in patient uptake in those Trusts and Health Boards that have moved

from postal to GP surgery return, showing that FIT pathways can be

flexible and adaptable to local requirements.


Without doubt, the COVID-19 pandemic has fundamentally changed

many clinical pathways in the health service. Many hope that some of

these innovative changes will continue into the future. This the widely

held opinion regarding the application of FIT, and the recent expansions,

past the original NG12 1 and DG30 2 guidelines, to use FIT in all patients

of all ages presenting with lower bowel symptoms, has provided a

clinically relevant investigation which now is a vital tool in the diagnosis

and treatment of CRC. With new logistics options, patient-centric

literature, and a sample collection device specifically designed for

patient-based sampling, the expansion of FIT will continue to support

endoscopy service for years to come, by helping avoid unnecessary

procedures, and allowing urgent referral for those most at risk of

significant bowel disease.

FIT-KITS have been developed by Alpha Laboratories, working in

collaboration with a large number of NHS and private healthcare

providers across the UK. If you would like to discuss your requirements

to facilitate an efficient process for rolling out FIT for your patients,

please contact

With thanks to Professor Callum G Fraser, Centre for Research into

Cancer Prevention and Screening, University of Dundee.


1. NICE. Suspected cancer: recognition and referral. NICE guideline

[NG12]. Last updated: 29 January 2021.

guidance/ng12 (Accessed 19 March 2021).

2. NICE. Quantitative faecal immunochemical tests to guide referral

for colorectal cancer in primary care. Diagnostics guidance [DG30].

Published date: 26 July 2017.

dg30 (Accessed 19 March 2021).

3. Colorectal Cancer Survival by Stage - NCIN Data Briefing. http://

survival_by_stage (Accessed 19 March 2021).

4. Ho KMA, Banerjee A, Lawler M, Rutter MD, Lovat LB. Predicting

endoscopic activity recovery in England after COVID-19: a national

analysis. Lancet Gastroenterol Hepatol 2021 Mar 10:S2468-

1253(21)00058-3. doi: 10.1016/S2468-1253(21)00058-3. Epub

ahead of print.


BM2025Pu-item-5-diagnostics-recovery-and-renewal.pdf (Accessed

19 March 2021).


(Accessed 19 March 2021).

7. Digby J, Strachan JA, McCann R, Steele RJ, Fraser CG, Mowat C.

Measurement of faecal haemoglobin with a faecal immunochemical

test can assist in defining which patients attending primary care

with rectal bleeding require urgent referral. Ann Clin Biochem

2020;57:325-7. doi: 10.1177/0004563220935622.

8. D’Souza N, Georgiou Delisle T, Chen M, Benton S, Abulafi M;

NICE FIT Steering Group. Faecal immunochemical test is superior

to symptoms in predicting pathology in patients with suspected

colorectal cancer symptoms referred on a 2WW pathway: a

diagnostic accuracy study. Gut 2020 Oct 21:gutjnl-2020-321956.

doi: 10.1136/gutjnl-2020-321956. Epub ahead of print.

9. Mowat C, Digby J, Strachan JA, McCann RK, Carey FA, Fraser

CG, Steele RJ. Faecal haemoglobin concentration thresholds for

reassurance and urgent investigation for colorectal cancer based

on a faecal immunochemical test in symptomatic patients in

primary care. Ann Clin Biochem 2021 Jan 21:4563220985547. doi:

10.1177/0004563220985547. Epub ahead of print.


(Accessed 19 March 2021).


11. Strachan JA, Mowat C. The use of faecal haemoglobin in

deciding which patients presenting to primary care require

further investigation (and how quickly) – the FIT approach.

eJIFCC 2021;32:52-60.

ejifcc2021vol32no1pp052-060.pdf (Accessed 19 March 2021).

12. Zahida Z, Carolyn P, Benton SC. Does visually over-loaded

HM-JACKarc collection device impact faecal haemoglobin

results? Ann Clin Biochem 2020 Dec 3:4563220976749. doi:

10.1177/0004563220976749. Epub ahead of print.

13. Benton SC, Symonds E, Djedovic N, Jones S, Deprez L, Kocna P,

Maria Auge J; International Federation of Clinical Chemistry Faecal

Immunochemical Test Working Group (IFCC FIT-WG). Faecal

immunochemical tests for haemoglobin: Analytical challenges

and potential solutions. Clin Chim Acta 2021 Feb 9;517:60-5. doi:

10.1016/j.cca.2021.01.024. Epub ahead of print.

14. Alpha Laboratories Ltd. Bespoke patient packs help support cancer

testing progress in the South West. Leading Edge. Vol. 2020, No. 1.

page_5.html (Accessed 23 March 2021).



How can you reduce the risk to

your Crohn’s disease patients

of serious COVID-19 disease? 1


Entocort ® CR:

classified by the

BSG as lowest risk

of serious COVID-19

disease, compared

to higher-risk

prednisolone 1

Entocort ® CR: BSG-recommended control patients can count on 1–3

Entocort ® CR is indicated for the induction

of remission in adults with mild to

moderate active Crohn’s disease affecting

the ileum and/or the ascending colon. 4

ENTOCORT CR 3mg Capsules (budesonide) -

Prescribing Information

Please consult the Summary of Product Characteristics

(SmPC) for full prescribing Information

Presentation: Hard gelatin capsules for oral administration

with an opaque, light grey body and an opaque, pink cap

marked CIR 3mg in black radial print. Contains 3mg

budesonide. Indications: Induction of remission in patients

with mild to moderate Crohn’s disease affecting the ileum

and/or the ascending colon. Induction of remission in patients

with active microscopic colitis. Maintenance of remission in

patients with microscopic colitis. Dosage and

administration: Active Crohn’s disease (Adults): 9mg once

daily in the morning for up to eight weeks. Full effect achieved

in 2-4 weeks. When treatment is to be discontinued, dose

should normally be reduced in final 2-4 weeks. Active

microscopic colitis (Adults): 9mg once daily in the morning.

Maintenance of microscopic colitis (Adults): 6mg once daily in

the morning, or the lowest effective dose. Paediatric

population: Not recommended. Older people: No special

dose adjustment recommended. Swallow whole with water.

Do not chew. Contraindications: Hypersensitivity to the

active substance or any of the excipients. Warnings and

Precautions: Side effects typical of corticosteroids may

occur. Visual disturbances may occur. If a patient presents

with symptoms such as blurred vision or other visual

disturbances they should be considered for referral to an

ophthalmologist for evaluation of the possible causes.

Systemic effects may include glaucoma and when prescribed

at high doses for prolonged periods, Cushing’s syndrome,

adrenal suppression, growth retardation, decreased bone

mineral density and cataract. Caution in patients with infection,

hypertension, diabetes mellitus, osteoporosis, peptic ulcer,

glaucoma or cataracts or with a family history of diabetes or

glaucoma. Particular care in patients with existing or previous

history of severe affective disorders in them or their first

degree relatives. Caution when transferring from

glucocorticoid of high systemic effect to Entocort CR. Chicken

pox and measles may have a more serious course in patients

on oral steroids. They may also suppress the HPA axis and

reduce the stress response. Reduced liver function may

increase systemic exposure. When treatment is discontinued,

reduce dose over last 2-4 weeks. Concomitant use of CYP3A

inhibitors, such as ketoconazole and cobicistat-containing

products, is expected to increase the risk of systemic side

effects and should be avoided unless the benefits outweigh

the risks. Excessive grapefruit juice may increase systemic

exposure and should be avoided. Patients with fructose

intolerance, glucose-galactose malabsorption or sucroseisomaltase

insufficiency should not take Entocort CR. Monitor

height of children who use prolonged glucocorticoid therapy

for risk of growth suppression. Interactions: Concomitant

colestyramine may reduce Entocort CR uptake. Concomitant

oestrogen and contraceptive steroids may increase effects.

CYP3A4 inhibitors may increase systemic exposure. CYP3A4

inducers may reduce systemic exposure. May cause low

values in ACTH stimulation test. Fertility, pregnancy and

lactation: Only to be used during pregnancy when the

potential benefits to the mother outweigh the risks for the

foetus. May be used during breast feeding. Adverse

reactions: Common: Cushingoid features, hypokalaemia,

behavioural changes such as nervousness, insomnia, mood

swings and depression, palpitations, dyspepsia, skin reactions

(urticaria, exanthema), muscle cramps, menstrual disorders.

Uncommon: anxiety, tremor, psychomotor hyperactivity.

Rare: aggression, glaucoma, cataract, blurred vision,

ecchymosis. Very rare: Anaphylactic reaction, growth

retardation. Prescribers should consult the summary of

product characteristics in relation to other adverse reactions.

Marketing Authorisation Numbers, Package

Quantities and basic NHS price: PL 36633/0006. Packs of

50 capsules: £37.53. Packs of 100 capsules: £75.05. Legal

category: POM. Marketing Authorisation Holder: Tillotts

Pharma UK Ltd, The Stables, Wellingore Hall, Wellingore,

Lincoln, LN5 0HX. Date of preparation of PI: February 2020

Adverse events should be reported.

Reporting forms and information can be found at Adverse events

should also be reported to Tillotts Pharma UK Ltd.

Tel: 01522 813500.


References: 1. Kennedy NA et al. Gut 2020; 0: 1–7. 2. Campieri M

et al. Gut 1997; 41(2): 209–214. 3. Lamb CA et al. Gut 2019; 0: 1–106.

4. Entocort ® CR 3 mg capsules – Summary of Product Characteristics.

Date of preparation: July 2020. PU-00377.



NHS trusts with:

2WW Urgent referrals

Routine referrals


Surveillance cases

Bowel cancer screening services


NHS Facility NHS Staff NHS




Enhanced sedation (Propofol) lists

Additionally, we can support Direct Access

and Rapid Access endoscopy referrals by

working with the local clinical leads to agree

strong governance for the management of

these patients.

Continuing Professional Development is an integral part of

a doctors life. Continuous learning in endoscopy is equally

important and furthers our technical skills, disease diagnosis and

management, decision making, recognition and avoidance of

complications, non-technical skills and ongoing care.

Criteria & Quality

We select Endoscopists with an endoscopy

orientated career path and performance

measures above the national average. JAG

audit data is constantly monitored to ensure

ongoing quality. Furthermore, we have a

Quality, safety and efficiency are central to our culture in 18 Weeks Support.

This is why we have partnered with GastroLearning, an endoscopic

educational platform pioneered by University College London consultants.

18 Week Support JAG quality standards generally exceed the UK

average (National Endoscopy Database) and our complications are

lower than those quoted by most studies. However our aims, through

rigorous governance, webinars and GastroLearning, are to enrich

education focussing on the following areas:

• Technical endoscopic skills

clinical governance department that is crucial

• Endoscopic diagnosis (detection and characterisation)

to maintaining quality and safety but also

provides support to both Endoscopists and

the units within which we work.

• Endoscopic management of disease (guidelines and therapy)

Covid has changed how professional education is delivered

The Covid pandemic has acted as a catalyst for a change in the approach

to providing medical education. However, changes in medical education

were already happening long before it’s unwanted arrival. The current and

younger generations of doctors, surgeons and allied health professionals

are more than competent digital learners. Education through digital channels

can be tailored by content and delivered very flexibly. “Snack” learning has

become particularly popular - everything you need to know on a subject in a

concise, clear format delivered by an engaging educator. Today’s generation

of practitioners are now less likely to see value – or to justify - the time and

expense involved in spending days in conference halls listening to lectures

that may or may not be relevant to their specific need or practice. The modern

approach in education is where GastroLearning excels.

We provide tailored solutions to manage

capacity from straight forward supply of staff

to a team based managed solution to a full

patient pathway including pathology review.

Our commitment to improving the

NHS Conference experience organisers must learn to adapt

Like the NHS Trusts we work with, patient

care is at the centre of everything we do. By

using any spare weekend capacity within a

Trust, the 18 Week Support insourcing teams

are able to see a high volume of patients

in a short space of time, in the familiar

surrounding of the NHS Trust.

Of course there is still a place for face-to-face conferences, both

from an educational and social networking point of view. Conference

organisers with an innovative and dynamic approach to education will

likely learn from the many new digital trends that have taken centrestage

in the past year. But some will not and will likely be less popular.

Whilst the past year has seen a plethora of digital learning events,

transplanting the traditional format of a conference online does not

work. Few can sit in front of a screen for an endless stream of lectures

for hours on end without interaction and there is little educational benefit

in doing so. Digital education is here to stay but it must be delivered in

an innovative fashion that meets the needs of the modern generation.

New ways of digital learning in CPD provision

An ethical company

We’re an ethical and transparent company

that’s financially accountable and financially

through a bespoke platform on iPad and, in November 2020, we

responsible. We’re committed to the NHS


and the delivery of high-quality care, and to

helping Trusts reduce RTT waiting times.

GastroLearning has been involved in the provision of Gastroenterology

education for over 10 years, most notably through running national and

international conferences. But we have always recognised the need to

modernise. For the past 3 years we have supplemented the traditional

face-to-face conference with the delivery of interactive digital education

launched our online platform which already has a global following.

Clinical team

All 18 Week Support Practitioners Access Free Education

Our weekly “Express Packages” published every Thursday provides a

selection of educational material utilising varying formats, from edited

video cases and 5 minute lectures to “Top Tips” presentations and

literature summaries. These Happy packages patient are aimed at covering important

topics in a concise fashion while catering for differing educational needs.

We also run a hugely popular 30 minute “Live Show” on the first

Wednesday of every month in which an expert is interviewed on a topic

relevant Who to we’re every Gastroenterologist. looking for The show is supplemented by

additional educational material to maximise the learning opportunities

We are interested in meeting with Consultant

and key topics are accompanied with interactive quizzes to reinforce the



Finally, we understand the




of social




and are

active on Twitter (@GastroLearn) with a rapidly rising number of followers.

Twitter nurse is becoming specialists an increasingly throughout popular method the for UK. individuals to

access and share education. It provides the opportunity to receive “snack”

learning and key messages can be shared, reaching a global platform.

Our remuneration package is second to

none and is per session rather than per case

which allows our teams to work in a safe and

calm environment’

All practitioners registered with 18 Week Support are able to access all

of this education content free of charge.

A future of effective partnerships and even newer


Ways in which CPD and its associated learning are delivered will

continue to evolve rapidly. Although digital approaches are already

the norm in many areas of medical education, there is an increasing

footprint of artificial intelligence and virtual reality in our day to day lives

About you

which provides immensely exciting possibilities to enhance education

further. GastroLearning and 18 Week Support will strive to be at the

forefront If you of have this and an ensure excellent high-quality NHS education record is delivered and to all of

its practitioners and to the wider gastroenterology community in the UK.

want to help clear NHS waiting list

backlogs, reduce RTT waiting times and

provide high-quality patient care, get in

If you have an excellent NHS record and want to help clear waiting

touch by calling on 020 3966 9081 or email

list backlogs, reduce RTT waiting times and provide high-quality

patient care, get in touch by calling on 0203 869 8790 or email us

Dr David Graham and Dr Matthew Banks

Join us: Follow us on Twitter: @Gastrolearn


Alternatively if you are procurer of 18 Week Support services,

please contact

18 Week Support

Dr Matthew Banks Banks

Clinical Lead for Gastroenterology

18 Week Support

London 3rd Floor, 19-21 Great Tower Street, London EC3R 5AR

Birmingham Unit 25, Lichfield Business Village, The Friary WS13 6QG






A first-line test to prioritise

gastroscopy referrals


BIOHIT HealthCare’s GastroPanel is a simple and effective

first-line test to diagnose Helicobacter pylori (H. pylori) and

atrophic gastritis in patients presenting with dyspepsia and

upper abdominal symptoms. Where endoscopy resources are

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identifying those at greatest risk in a primary care setting prior

to referral.

Chronic H. pylori infection is the primary cause of atrophic

gastritis – a condition of the gastric mucosa considered to be

the greatest independent risk factor for developing gastric

cancer – and current guidance recommends that individuals

with extensive gastric atrophy undergo regular endoscopic

surveillance to closely monitor their disease progression.

Early detection of those individuals with a significant risk

of developing gastric cancer is the key to effective patient

management, helping to reduce unnecessary referrals, and

improving survival rates through earlier diagnoses.

GastroPanel comprises reliable and automatable assays

for four stomach-specific biomarkers, enabling thorough

and objective investigation of the whole gastric mucosa, and

offering clinicians more confidence in their diagnoses. The

highly specific IgG antibody test for identifying H. pylori is

combined with the analysis of pepsinogen I, pepsinogen II and

gastrin-17 to establish the structure and function of the entire

gastric mucosa. Implementing this first-line diagnostic test

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effectively ruling out gastrointestinal (GI) diseases for others.

This patient-friendly blood test can help transform the

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GastroPanel is a simple, effective and low cost blood test for

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By Alice Andrews, Coeliac UK

Coeliac disease (CD) is a systemic autoimmune condition,

characterised by enteropathy of the small intestine, triggered

by dietary gluten in genetically susceptible individuals. CD

is estimated to affect 1% of the UK population however, only

around 30% of those with the condition have been diagnosed

[1]. The clinical presentation of CD varies from intestinal and

extraintestinal symptoms to asymptomatic presentations, making

diagnosis challenging for healthcare professionals.

Recent research published in the Journal of Pediatric Gastroenterology

and Nutrition has demonstrated excellent uptake of no-biopsy diagnosis

guidelines, but sheds light on variations in follow up care amongst 29

specialist paediatric gastroenterology centres in the UK [2].

Diagnosis via the no biopsy pathway

In 2012, European Society for Paediatric Gastroenterology, Hepatology and

Nutrition (ESPGHAN) revised guidelines to allow some children with CD to

be diagnosed without having a duodenal biopsy. Within these guidelines, a

no biopsy pathway was suitable for symptomatic children who:

• have IgA based anti-tissue transglutaminase antibodies (TGA-IgA)

>ten times the upper limit of normal

• positive anti-endomysial antibodies (EMA-IgA)

• Positive HLA-DQ2/DQ8 haplotype.

These guidelines have since been updated in 2020 with two notable

changes. Diagnosis can now be made without the need for HLA-DQ2/

DQ8 testing and secondly, a no biopsy approach can also be offered to

asymptomatic children [3].

NICE guidelines recommend that the need for a DEXA scan should

be considered on an individual basis at annual review [5]. A minority

(4/29) of centres reported that they performed routine DEXA scan post

diagnosis and some centres only offered a scan if there was a risk of

fractures or reported low vitamin D levels. Most children do not need to

have a DEXA scan as early diagnosis and adherence to the GFD has

been shown to improve bone density.

Most centres (28/29) routinely measured vitamin D status but practice

around supplementation varied. Most centres based their approach on

vitamin D levels, but in some centres vitamin D supplements are offered

to all CD patients regardless of their vitamin D status.

Since 2015, NICE guidelines have recommended that patients can

introduce gluten free (GF) oats to the diet at any stage [5]. GF oats add

variety to the gluten free diet and are also a good source of soluble fibre

but a small minority of people with CD are sensitive to GF oats. Less

than a third of centres recommended that children included GF oats

from diagnosis and the majority of centres waited until normalisation of

TGA-IgA before introducing GF oats to the diet [2].

New developments in paediatric coeliac

disease management

As there is limited research to inform the best management strategies,

current guidance is based on expert consensus opinion. There is a

need for more research in this area and an opportunity to undertake

prospective research to assess different follow up strategies.

An infographic summarising this publication is available at http://links.


The survey carried out in 2019 concluded that in the UK, there was

excellent uptake of the ESPGHAN 2012 diagnostic guidelines, with 76%

centres (n=22) adopting the no biopsy pathway by 2013. Diagnosis

should only be made by a paediatric gastroenterologist or consultant

paediatrician with a special interest in CD however, at some UK centres

the diagnosis is made by a general paediatrician [4] or an expert dietitian.

Follow up care

The research also investigated follow up care and found discrepancies

across the UK [2]. Adopting a gluten free diet (GFD) is challenging

for children and their families as they face several difficulties, from

the increased cost of gluten free staple foods to school meals and

socialising with friends, which can all affect their quality of life and

adherence to the diet. For this reason, regular follow ups are important

for providing support and help maintaining adherence to the GFD.


[1] West, J. et al. (2019) “Changes in Testing for and Incidence of Celiac Disease in

the United Kingdom,” Epidemiology. Ovid Technologies (Wolters Kluwer Health),

30(4) e23–e24. doi: 10.1097/ede.0000000000001006.

[2] Paul, S. P. et al. (2021) “Celiac disease management in the United Kingdom

specialist pediatric gastroenterology centers – a service survey” Journal

of Pediatric Gastroenterology and Nutrition. 2021 Mar 17. doi: 10.1097/


[3] Husby, S. et al. (2019) European Society Paediatric Gastroenterology, Hepatology

and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. Journal of

Pediatric Gastroenterology and Nutrition. 70(1):141-156. doi: 10.1097/


[4] Paul S. P. et al. (2019) “HLA-DQ2/DQ8 typing for non-biopsy diagnosis of

coeliac disease: is it necessary?” Arch Dis Child. 104:1119-20. doi: 10.1136/


[5] National Institute for Health and Care Excellence (2015). Coeliac disease:

recognition, assessment and management. NICE guidelines 20. NICE, London.

Available at [Accessed 27.04.2021]



maintenance therapy

for ulcerative colitis:



When mesalazine doesn’t seem to be working, stepping

up to immunosuppressants isn’t the only option

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pleasant vanilla flavour, and they’re a proven way to

help patients get the most from their mesalazine 1-3

Optimising therapy with once-daily Salofalk Granules in patients

who were inadequately maintained on previous mesalazine resulted in: 2

69% 45% 50%



off work


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courses used

Mesalazine, the Dr Falk way

Prescribing Information (refer to full SPC before prescribing):

Salofalk gastro-resistant prolonged-release granules

Presentation: Stick-formed or round, greyish white gastro-resistant

prolonged-release granules in sachets containing 500mg, 1000mg,

1.5g or 3g mesalazine per sachet. Indications: Treatment of acute

episodes and the maintenance of remission of ulcerative colitis.

Dosage: Adults: Once daily 1 sachet of 3g granules, 1 or 2 sachets of

1.5g granules or 3 sachets of 1000mg or 500mg granules (equivalent

to 1.5 – 3.0g mesalazine daily) preferably taken in the morning,

according to individual clinical requirement. May be taken in three

divided doses (1 sachet of 500mg granules three times daily or 1

sachet of 1000mg granules three times daily) if more convenient.

Maintenance: 0.5g mesalazine three times daily (morning, midday

and evening) corresponding to a total dose of 1.5g mesalazine

per day. For patients known to be at increased risk for relapse

for medical reasons or due to difficulties to adhere to three daily

doses, give 3.0g mesalazine as a single daily dose, preferably in the

morning. Children: There is only limited documentation for an effect

in children (age 6-18 years). Children 6 years of age and older: Active

disease: To be determined individually, starting with 30-50mg/

kg/day once daily preferably in the morning or in divided doses.

Maximum dose: 75mg/kg/day. The total dose should not exceed the

maximum adult dose. Maintenance treatment: To be determined

individually, starting with 15-30mg/kg/day in divided doses. The

total dose should not exceed the recommended adult dose. It is

generally recommended that half the adult dose may be given to

children up to a body weight of 40kg; and the normal adult dose to

those above 40kg. Method of administration: Taken on the tongue

and swallowed, without chewing, with plenty of liquid. Contraindications:

Hypersensitivity to salicylates or any of the excipients.

Severe impairment of renal or hepatic function. Warnings/

Precautions: Blood tests and urinary status (dip sticks) should be

determined prior to and during treatment. Caution is recommended

in patients with impaired hepatic function. Should not be used in

patients with impaired renal function. Mesalazine-induced renal

toxicity should be considered if renal function deteriorates during

treatment. Cases of nephrolithiasis reported; ensure good hydration.

Patients with pulmonary disease, in particular asthma, should be

carefully monitored. Patients with a history of adverse drug reactions

to preparations containing sulphasalazine should be kept under close

medical surveillance. If acute intolerance reactions e.g., abdominal

cramps, acute abdominal pain, fever, severe headache and rash,

occur, stop treatment immediately. Severe cutaneous adverse

reactions (SCARs), including Stevens-Johnson syndrome (SJS) and

toxic epidermal necrolysis (TEN), have been reported. Discontinue

treatment at the first appearance of signs and symptoms of severe

skin reactions, such as skin rash, mucosal lesions, or any other sign

of hypersensitivity. Salofalk granules contain aspartame, a source of

phenylalanine that may be harmful for patients with phenylketonuria.

Salofalk granules contain sucrose: 0.02mg, 0.04mg, 0.06mg and

0.12mg (500mg/1g/1.5g and 3g granules respectively). Interactions:

Specific interaction studies have not been performed. Lactulose

or similar preparations that lower stool pH: possible reduction of

mesalazine release from granules due to decreased pH caused by

bacterial metabolism of lactulose. With concomitant treatment with

azathioprine, 6-mercaptopurine or thioguanine consider a possible

increase in their myelosuppressive effects. There is weak evidence

that mesalazine might decrease the anticoagulant effect of warfarin.

Use in pregnancy and lactation: There are no adequate data. Do

not use during pregnancy unless the potential benefit outweighs

the possible risks. Limited experience in the lactation period. Use

during breast-feeding only if the potential benefit outweighs the

possible risks; if the infant develops diarrhoea, breast-feeding

should be discontinued. Undesirable effects: Headache, dizziness,

peri- and myocarditis, abdominal pain, diarrhoea, dyspepsia,

flatulence, nausea, vomiting, aplastic anaemia, agranulocytosis,

pancytopenia, neutropenia, leukopenia, thrombocytopenia,

peripheral neuropathy, allergic and fibrotic lung reactions

(including dyspnoea, cough, bronchospasm, alveolitis, pulmonary

eosinophilia, lung infiltration, pneumonitis), acute pancreatitis,

impairment of renal function including acute and chronic interstitial

nephritis and renal insufficiency, nephrolithiasis, photosensitivity

especially with pre-existing skin conditions, alopecia, Stevens-

Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), myalgia,

arthralgia, hypersensitivity reactions such as allergic exanthema,

drug fever, lupus erythematosus syndrome, pancolitis, changes in

hepatic function parameters, hepatitis, cholestatic hepatitis and

oligospermia (reversible), asthenia, fatigue, changes in pancreatic

enzymes, eosinophil count increased. Legal category: POM. Basic

cost: Salofalk 500mg granules, pack size 100 sachets - £28.74;

31.47€. Salofalk 1000mg granules, pack size 50 sachets – £28.74;

32.87€. Salofalk 1.5g Granules, pack size 60 sachets - £48.85;

51.29€. Salofalk 3g Granules pack size 60 sachets - £97.70; 104.06€

(UK- NHS price; IE - PtW). Product licence number: Salofalk 500mg

granules – PL08637/0007; PA573/3/1. Salofalk 1000mg granules –

PL08637/0008; PA573/3/2. Salofalk 1.5g granules PL08637/0016;

PA573/3/7. Salofalk 3g granules PL08637/0025; PA573/3/6. Product

licence holder: Dr Falk Pharma GmbH, Leinenweberstr.5, D-79108

Freiburg, Germany. Date of preparation: November 2020

Further information is available on request.


Adverse events should be reported. Reporting forms and

information can be found at

(UK residents) or in Ireland at

about-us/report-an-issue/human-adverse-reaction-form. Adverse

events should also be reported to Dr Falk Pharma UK Ltd at


1. Salofalk Granules. Summary of Product Characteristics.

2. Aldulaimi D et al. Poster DRF16/057 presented at the BSG

Annual Meeting, June 2016, Liverpool UK.

3. Keil R et al. Scand J Gastroenterol 2018; 21: 1-7.

UC: ulcerative colitis


Date of preparation: January 2021 DrF 20/226






Karoline Freeman 1* , Ronan Ryan 2 , Nicholas Parsons 1 , Sian Taylor‐Phillips 1 , Brian H. Willis 2 and Aileen Clarke 1

Freeman et al. BMC Gastroenterol (2021) 21:139


Background: Our knowledge of the incidence and prevalence of

inflammatory bowel disease (IBD) is uncertain. Recent studies reported

an increase in prevalence. However, they excluded a high proportion

of ambiguous cases from general practice. Estimates are needed to

inform health care providers who plan the provision of services for IBD

patients. We aimed to estimate the IBD incidence and prevalence in UK

general practice.

Methods: We undertook a retrospective cohort study of routine electronic

health records from the IQVIA Medical Research Database covering 14

million patients. Adult patients from 2006 to 2016 were included. IBD was

defined as an IBD related Read code or record of IBD specific medication.

Annual incidence and 12-month period prevalence were calculated.

Results: The prevalence of IBD increased between 2006 and 2016 from

106.2 (95% CI 105.2–107.3) to 142.1 (95% CI 140.7–143.5) IBD cases

per 10,000 patients which is a 33.8% increase. Incidence varied across

the years. The incidence across the full study period was 69.5 (95% CI

68.6–70.4) per 100,000 person years.

Conclusions: In this large study we found higher estimates of IBD

incidence and prevalence than previously reported. Estimates are highly

dependent on definitions of disease and previously may have been


Keywords: Inflammatory bowel disease, Primary health care,

Epidemiology, Electronic health care records



Inflammatory bowel disease (IBD) includes a group of related, chronic

relapsing disorders. They place significant demand on healthcare

resources including consultation time, testing and treatment. In order

to plan healthcare resources, knowledge of the size of the problem

is required. This can be inferred from the incidence and prevalence

of IBD in the population. A recent systematic review published in the

Lancet assessed the incidence and prevalence of IBD around the

world [1]. Studies using UK data from the 1990s reported incidence

rates ranging from 21 to 32.2/100,000 [2–4] and prevalence estimates

ranging from 328 to 409/100,000 [2, 5–7]. The review suggested that

incidence rates have stabilised in the western world, while other studies

reported an ongoing increase in incidence rates [8, 9]. Two recent UK

studies, that excluded a high proportion of ambiguous diagnoses from

general practice, reported considerably higher prevalence estimates

of 725–781/100,000 [10,11]. A third recent study reported estimates

for ulcerative colitis and Crohn’s disease but excluded cases of IBD

unclassified (IBDU) [12]. However, IBD cannot be classified in 20–30%

of patients at first presentation and 13% remain unclassified 1 year

later [13]. This may have resulted in underestimates of the true IBD

prevalence in UK general practice. Our aim is to establish estimates of

incidence and prevalence of IBD in adult patients in UK general practice

using routine primary care electronic health records.

UK primary care data, such as the IQVIA Medical Research Database

(IMRD-UK) [formerly known as the Health Improvement Network (THIN)],

are unique and particularly suitable for research. Over 95% of the UK

population is registered with a GP [2, 14]. General practitioner (GPs)

act as gatekeepers to all services and specialists in secondary care

(excluding emergency care). Patients are usually only registered with one

GP at any one point in time; and for each patient the registration date

and the date when the patient leaves the practice is known. This provides

longitudinal data with known start and end date of follow-up. The role of

the GP extends to the management of chronic patients.

The IMRD population is broadly representative of the UK population and

prevalence of chronic diseases is comparable to national rates [15]. Findings

can be generalised to the broader UK primary care population [15].


Data source

Study data consisted of electronic health care records available in

the IMRD. The IMRD consists of anonymised, longitudinal individual

level patient data from more than 670 UK GP practices using the

Vision practice software. In 2015 a total of over 14 million patients had

contributed data to IMRD which reflects a coverage of about 6% of the

UK population [16]. Data are based on patient consultation information

including symptoms, diagnoses, investigations and medications recorded

as clinical codes. Data were included into the study from GP practices

from the date that the practice was deemed to be reporting all-cause

mortality reliably compared to national statistics and from 1 year after the

installation of the electronic medical record system. We applied these

quality control measures to ensure data reliability and completeness.

The IMRD has received Research Ethics Committee approval by the

NHS South-East Multicentre Ethics Committee for research as a whole.

Scientific Review Committees (SRCs) have been established to review

IMRD study protocols for scientific merit and feasibility. This project was

given approval by the SRC (SRC Reference Number 17THIN089) on

23rd October 2017.





Warwick Medical School, University of Warwick, Coventry, UK

Full list of author information is available at the end of the article


Study design and study population

We undertook a retrospective cohort study of patients with data in the

IMRD who were at least 18 years of age during the period 1 January

2006 to 31 December 2016. The study cohort was dynamic with patients

entering and exiting the study at different times. Patients entered the

study 1 year after they registered with the GP practice or at age 18 years,

whichever came later. Patients exited the study at the earliest of the

following dates: deregistration with the practice; death; or 1 January 2017.

Definition of IBD diagnosis

The outcome of interest was newly diagnosed IBD. We searched the

medical records of the study population for patients with a diagnosis of IBD.

Those with a clinical code indicative of IBD and/or at least one prescription

of an IBD specific medication in the patient record were classified as cases

of IBD. The date of IBD diagnosis was taken as the first occurrence of a

clinical code for IBD or first prescription of IBD specific medication in the

patient record. We were interested in the broad category of inflammatory

bowel disease and included clinical codes for general IBD, ulcerative colitis,

Crohn’s disease, indeterminate colitis and microscopic colitis. Clinical

code lists were adapted from those used in previous literature [6, 17].

IBD specific medication included mesalazine, olsalazine and balsalazide.

Sulfasalazine, prednisolone and budesonide preparations were considered

IBD specific if rectal. Preparations of beclometasone needed to clearly

specify use for the bowel to be included. Therefore, the definitions for

medications were purposefully narrow and decisions on inclusion were

exclusive if in doubt. The complete code list to identify IBD diagnoses is

available in Additional file 1.


The annual incidence and 12-month period prevalence of IBD were

determined for 2006–2016 considering all adult patients contributing

data to IMRD in that period. Annual incidence was defined as the

number of new cases of IBD during a 1 year period over the total time

each patient was observed (person-time at risk). Period prevalence was

defined as new and pre-existing IBD cases during a 12-month period

over the number of patients in the IMRD database during the same time

period. Confidence intervals for incidence rates were exact Poisson

confidence limits. Confidence intervals for prevalence were calculated

using the Wilson procedure for proportions without a correction for

continuity. Incidence rates for male and female patients were compared

using the two sample z test.

All analyses were undertaken in R version 3.6.1 (Vienna, Austria)

[18]. The package “epitools” was used to calculate exact confidence

intervals for incidence rates [19]. Graphs were drawn using the package

“ggplot2” [20].


IBD incidence and prevalence

We retrieved 6,965,853 records of adult patients from the IMRD

database and excluded 33,730 patients who entered the study after the

study period (Fig. 1). We included a total of 6,932,123 patients in the

analysis of IBD prevalence. The prevalence of IBD increased between

2006 and 2016 from 106.2 (95% CI 105.2–107.3) to 142.1 (95% CI

140.7–143.5) IBD cases per 10,000 in the adult IMRD population with

an average increase of 2.96% per annum. This amounts to an increase

of 33.8% from 2006 to 2016. More women than men had a recorded

diagnosis of IBD (Fig. 2).

We excluded 61,125 prevalent IBD cases from the dataset which

resulted in a dataset of 6,870,998 patients for the analysis of IBD

incidence (Fig. 1). There were 25,470 IBD incidence cases between

2006 and 2016. 4736 (18.6%) had an IBD Read code only, 9632 (37.8%)

had a prescription of an IBD medication only and 11,102 (43.6%) had

both. Incidence of IBD in the adult IMRD population varied across

the years with a maximum of 76.4 (95% CI 73.6–79.4) per 100,000

recorded in 2010 and the lowest incidence of 63.5 (95% CI 60.4–66.7)

per 100,000 recorded in 2016 (Fig. 3). The incidence across the full

study period was 69.5 (95% CI 68.6–70.4) per 100,000 person years.

The incidence rate was higher in women than men for the study period

(73.09 versus 65.83, z = 8.3, p < 0.0001).


Fig. 1 Overview of inclusion and exclusion of cases for the analyses of IBD incidence and prevalence

Fig. 1 Overview of inclusion and exclusion of cases for the analyses of IBD incidence and prevalence



Fig. 2 12‐month period prevalence of IBD per 10,000 adult IMRD population

Fig. 2 12-month period prevalence of IBD per 10,000 adult IMRD population


Summary of study findings

The analyses of IBD prevalence and incidence included a total of

6,932,123 and 6,870,998 adult patients, respectively. The prevalence of

IBD in 2016 was 142.1 (95% CI 140.7–143.5) per 10,000 adult patients.

The prevalence of IBD increased between 2006 and 2016 by 33.8%.

This is likely due to the fact that IBD is a chronic condition which is

associated Fig. 2 with 12‐month a low mortality period prevalence rate. The of mean IBD per IBD 10,000 incidence adult IMRD for the population

study period was 69.3 (95% CI 66.8–71.8) per 100,000 person years.

The drop in incidence between 2010 and 2011 may be an artefact or

caused by an administrative change in coding/reporting standards.

Over the most recent 5-year period, the incidence of IBD was relatively


Study strengths and limitations

The IQVIA Medical Research database is a rich source of routine

electronic health care records of patients managed in primary care

and is particularly useful for the study of real world problems. The

study population was large and covered nearly 50% of all UK Clinical

Commissioning Groups [16] meaning that findings are generalisable to

UK primary care in general.


Fig. 3 Annual IBD incidence per 100,000 person‐years in the adult IMRD population

Fig. 3 Annual IBD incidence per 100,000 person‐years in the adult IMRD population

Fig. 3 Annual IBD incidence per 100,000 person-years in the adult IMRD population



The criterion “registration date plus 1 year” to assess patients’ eligibility

for study inclusion avoided the systematic over-reporting of incidence

rates in the first year of follow-up for newly registered patients [21]. It

also prevented the double counting of prevalent cases when patients

transfer from one IMRD practice to another.

Limitations that might have affected the research are linked to

characteristics of routine data.

IBD diagnoses might be missing either due to incorrect coding,

missed coding or recording as free-text. This might have led to an

underestimation of IBD incidence and prevalence. However, we

included a record of an IBD specific medication in the definition of an

IBD diagnosis which mitigated the effect. This may explain our higher

figures for IBD incidence and prevalence when compared to a recent

study which only included patients with two IBD Read codes recorded

or one IBD Read code and an IBD drug code [11].

Potential misclassification through miscoding of ulcerative colitis as

Crohn’s disease and vice versa, or by using higher order codes rather

than disease specific codes was of no consequence to our study. We

were interested in the broad category of inflammatory bowel disease

rather than sub-category, severity or location of disease. We were

able to include codes for IBD and indeterminate IBD and present the

complete picture of IBD in primary care which is in contrast to a recent

study which only focused on patients with a diagnosis of ulcerative

colitis or Crohn’s disease [12].

A limitation of our study may be our inability to verify IBD cases. While

we mitigated against under-coding, over-coding is a possibility. A study

reported that about 6% of IBD codes did probably not relate to a true

IBD diagnosis [6]. However, the study relied on confirmatory data from

GP questionnaires and considered coded data from 20 years ago.

Findings in the context of existing literature

Published figures on UK IBD incidence rates range from 21 to

37.5/100,000 [2–4, 10–12]. Studies consistently report that prevalence

is rising worldwide because of the low mortality associated with this

chronic condition. UK prevalence estimates range from 328/100,000 in

the 1990s [6] to 970/100,000 in 2017 [12].

Our estimates of incidence and prevalence of IBD in the UK are about

1.8 and 1.5 times higher than the most recent estimates. Published

studies are very heterogeneous, complicating comparison of reported

rates across studies. Major variations that explain at least some of the

differences include: (1) our study included adult patients only, while

the majority of other studies covered a wider age range including

children. This impacts the incidence and prevalence rates of IBD which

has an onset that peaks in adulthood. (2) Improvements in diagnostic

technology now enable the detection of milder cases [9]. (3)

Some smaller studies used GP records to identify cases with

subsequent exclusion of unverified cases. Exclusions ranged from 8

to 26% of patients [2, 3, 10]. This could have underestimated true IBD

prevalence. (4) Studies used different definitions of disease. A number

of studies did not include indeterminate IBD or microscopic IBD in

their definition. A recent study reported the incidence and prevalence

of ulcerative colitis and Crohn’s disease in the IMRD-UK database

[12]. The study only included Read codes for Crohn’s disease and

ulcerative colitis in the definition of disease. In contrast we used a very

comprehensive and sensitive list of Read codes and drug codes (48

codes) for the identification of IBD, ulcerative colitis, Crohn’s disease,

indeterminate IBD and microscopic colitis. In addition, a previous study

using the IMRD-UK data used a similar list of Read codes to our study

for the identification of IBD. However, they included non-specific IBD

medications to identify IBD cases and only included patients with at

least two subsequent IBD records or an IBD record and a recorded

prescription of an IBD related drug [11]. According to our data, this

approach may have missed at least 37.8% of cases. We were able

to increase the sensitivity of our Read code list by using medications

to identify additional IBD cases because we restricted inclusion of

prescriptions to IBD specific medications. This is an advantage of our

study over these two recent IMRD-UK studies.

Implications for research and practice

Taken together, the evidence suggests that the IBD incidence and

prevalence in the UK adult population may be higher than the latest

published figures. Some of the differences in reported rates may be

due to differences in methodology including differences in methods

of case definition [22]. Case definition is complicated by the fact that

IBD is a heterogeneous group of disorders. Crohn’s disease and

ulcerative colitis are considered as the two extremes of a spectrum

of chronic gut disorders [23]. Furthermore, the phenotype of IBD is

not uniform resulting in IBD unclassified cases [13, 24]. The overlap

with other infectious, inflammatory and autoimmune disorders led to

suggestions to diverge from the classification of IBD into ulcerative

colitis and Crohn’s disease and to reclassify IBD considering a broader

disease spectrum [25]. This argues for a broader definition of IBD in the

estimation of IBD incidence and prevalence.


In this large study we found higher estimates of IBD incidence and

prevalence than previously reported. Estimates are highly dependent on

definitions of disease and previously may have been underestimated.

We believe that our sensitive approach to identifying IBD cases may

be more reflective of the true burden of disease in UK general practice.

Health care providers who plan services for IBD patients need to make

allowances for these updated figures and should consider the definition

of disease in published studies.


IBD: Inflammatory bowel disease; IMRD: IQVIA Medical Research

Database; THIN: The health improvement network; GP: General

practitioner; CI: Confidence interval; IBDU: IBD unclassified.

Supplementary Information

The online version contains supplementary material available at https:// s12876-​021-​01716-6.

Additional file 1. Complete list of clinical and drug codes for the

identification of IBD diagnoses in electronic health records.


Not applicable

Authors’ contributions

KF, STP, BHW, RR and AC designed the study. RR extracted the data

from IMRD and created the datasets. KF and NP carried out the

analysis. KF, BHW, STP, NP and AC contributed to the interpretation of

the findings. KF drafted the manuscript. All authors read and approved

the final manuscript. KF takes responsibility for the integrity and

accuracy of the data analysis. KF acts as guarantor. The corresponding

author attests that all listed authors meet authorship criteria and that no

others meeting the criteria have been omitted.






KF is funded by a National Institute for Health Research (NIHR) DRF

award (DRF-2016-09-038) for this research project. AC is supported

by the National Institute for Health Research (NIHR) Applied Research

Collaboration (ARC) West Midlands. This report presents independent

research funded by the National Institute for Health Research (NIHR).

The views expressed are those of the authors and not necessarily those

of the NHS, the NIHR or the Department of Health and Social Care. The

funder had no role in the study design, data collection, data analysis

and interpretation, writing of the report or the decision to submit for


Availability of data and materials

The datasets generated during and/or analysed during the current study

are not publicly available under the data sharing agreement with the

University of Birmingham on behalf of IQVIA.


Ethics approval and consent to participate

Anonymised data were provided by the data provider IQVIA. Studies

using IMRD have initial ethics approval from the NHS South-East

Multicentre Ethics Committee, subject to prior independent scientific

review. The Scientific Review Committee (IQVIA) approved the study

protocol (SRC reference number 17THIN089).

Consent for publication

Not applicable.

Competing interests

The authors declare: KF is funded by the NIHR through a doctoral

research fellowship. AC is supported by the NIHR ARC West Midlands

initiative. STP is funded by the NIHR through a career development

fellowship (NIHRCDF-2016-09-018). BHW reports grants from the

Medical Research Council. RR and NP have nothing to declare.

Author details


Warwick Medical School, University of Warwick, Coventry, UK.


Institute of Applied Health Research, University of Birmingham,

Birmingham, UK.

Received: 23 September 2020 Accepted: 10 March 2021

Published online: 26 March 2021


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Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in

published maps and institutional affiliations.








Massardi C, Cooney J, Poullis A, Department of Gastroenterology, St George’s Hospital, London

Case Study

A 29-year-old male had attended the Emergency Department

on several occasions over the previous month with worsening

abdominal pain, constipation, nausea and vomiting. He had

no past medical or surgical history and worked as a builder

and decorator. There was no significant smoking or alcohol

history and he had no known family history of gastrointestinal

disease. Clinical examination was unremarkable. No cause

had been found for his symptoms so he was referred to the

Gastroenterology outpatient clinic.

Routine blood tests showed deranged liver function tests (LFTs), with

elevated bilirubin (31 umol/L) alanine transaminase (192 units/L) and

gamma-glutamyl transferase (65 iU/L) Autoimmune and viral liver

screens were negative. Ultrasound of the liver was normal apart from

some hyperechogeneity in the liver in keeping with fatty infiltration.

An abdominal radiograph was performed which found small specks

of high attenuation material in the colon [Figure 1]. A porphyria

screen was arranged due to the unclear aetiology of the patient’s

symptoms and blood tests.

The patient’s urine porphyria screen was found to be abnormal, with

a porphyrin/creatinine ratio of 472 nmol/mmol creatinine, therefore

further porphyria assays were requested.


These demonstrated a porphobilinogen of 27.8 umol/L (normal



of toxicity. Clinical manifestations of lead toxicity are varied and can

be non-specific. Acute toxicity often manifests as abdominal pain,

constipation, body pains, decreased libido, headaches, memory

problems and irritability. Chronic exposure can produce anaemia,

reduced neuro-cognitive function, nephropathy, tremor, hearing loss

and hypertension 2 .

In the paediatric population lead toxicity risks significant and

irreversible neurodevelopmental damage and should be investigated

in any child presenting with an unexplained alteration in mental

state and behavioral changes in the presence of risk factors for lead

exposure 3 .

An elevated blood lead level reflects recent exogenous exposure as

well as release of endogenous lead from bone and soft tissue stores.

Toxicity is thought to develop due to lead competing with calcium in

several biological processes, inhibiting enzymes, and altering the

permeability of the blood brain barrier.

The mainstay of management is the separation of the patient from

the source of the lead exposure. In patient with very elevated lead

levels (>50 mcg/dL) or symptoms of acute toxicity chelation therapy

can be considered under specialist guidance 4,5 . The two most

commonly used chelating agents are DMSA (2,3-dimercaptosuccinic

acid) or EDTA (calcium disodium ethylenediaminetetraacetic acid).

Chelation should not be undertaken unless exposure to lead has

been curtailed, as in the presence of ongoing lead exposure,

chelation may lead to enhanced absorption of lead and therefore

worsening toxicity.

Regular and long-term monitoring of lead levels is required until

normal levels are achieved, as lead can be stored in bone for several

decades. Patients with established sequelae of lead toxicity such as

cardiovascular disease, cognitive dysfunction and renal failure are

unlikely to see reversibility of their symptoms over time even with

chelation therapy.


Lead toxicity is an uncommon yet important differential in patients

presenting with persistent abdominal pain. Prompt diagnosis and

subsequent treatment is imperative in negating the potentially long-term

damaging effects of lead on multiple organ systems. In these patients,

a through social history is the most crucial, but often overlooked, step in

reaching the diagnosis.


1. J. Route Reigart, British Medical Journal Best Practice

Guidelines; Approach to Lead Toxicity. Updated 17th April 2021.

2. National Toxicology Program. Health effects of low-level lead

evaluation. Research Triangle Park, NC: US Department of Health

and Human Services; 2012.


3. D. A. Gildow, Lead Toxicity, Occupational Medicine 2004;54:76–81

DOI: 10.1093/occmed/kqh019

4. Lin JL, Ho HH, Yu CC. Chelation therapy for patients with

elevated body lead burden and progressive renal insufficiency. A

randomized, controlled trial. Ann Intern Med 1999; 130:7.

5. Association of Occupational and Environmental Clinics. Medical

management guidelines for lead-exposed adults. April 2007. http://

6. Centres for Disease Control (CDC) and Prevention. Adult blood lead

epidemiology and surveillance (ABLES).


Table 1: Risk Factors for Lead Exposure 1


Pica syndrome

Housing environment


Recreational activities

Traditional / herbal medicines

Children between the ages of 9-36 months are at the most risk of ingesting lead-containing substances in

their environment.

Compulsive ingestion of material with no nutritional value. Most commonly seen in children and pregnant


Older homes (built before 1970) may have lead piping or lead paint.

Any job that involves handling material that may include lead, especially construction and decorating. The

risk is increased if the job entails sanding down walls or removing paint which generates a fine dust of lead

particles that are easily inhaled and ingested.

Including painting, figurine or jewelry making and stained glass making.

Any herbal remedy may contain lead. Most common sources are Ba- baw-san (traditional Chinese remedy

for colic), Daw Tway (used in Thailand and Burma as a digestive aid), Greta (traditional Hispanic remedy

for digestion or used during teething) and Ghasard (Indian folk medicine used as a tonic)







Zhijie Lv 1 , Xiaoqi Zhang 2 and Li Wu 3*

Lv et al. BMC Gastroenterol (2021) 21:193


Background: Infliximab-induced seizures in patients with Crohn’s

disease are extremely rare and the mechanism of infliximab-induced

seizures is unclear.

Case presentation: A 60-year-old woman with Crohn’s disease

experienced infliximab-induced seizures, diagnosed on normal

magnetic resonance imaging of the brain. Moreover, the rechallenge

with infliximab was positive.

Conclusions: Neurological assessment and tight clinical monitoring

before and during therapy with infliximab should be performed in

patients with pre-existing seizure disorders.

Keywords: Infliximab, Seizures, Crohn’s disease, Case report



Infliximab is currently used as the first-line treatment for Crohn’s

disease(CD). During the 20 years since its first approval in 1998,

infliximab has revolutionized the treatment of inflammatory bowel

disease(IBD). Over half a million patients have been treated with tumor

necrosis factor (TNF)-α antagonists, but concerns regarding their

safety have been raised worldwide [1].The most commonly reported

adverse reactions to infliximab include acute or delayed hypersensitivity

reactions; serious infections including reactivation of tuberculosis and

hepatitis B virus; malignancy, especially lymphoma and hematologic

reactions [2, 3]. However, new and rare side-effects have been

increasingly reported in post-marketing reports. Here, we have reported

a rare case of a patient with CD who experienced infliximab-induced

seizures, diagnosed on normal magnetic resonance imaging (MRI) of

the brain. Moreover, the rechallenge with infliximab was positive.

Case presentation

A 60-year-old female presented to our hospital with a 10-day history of

small intestinal stenosis due to CD. The patient was diagnosed with CD

in 2015 due to chief complaints of abdominal pain and watery diarrhea

(3−4 times per day). The patient’s medical history was unremarkable.

She was treated with mesalazine (3 g/day), which partially alleviated the

symptoms of abdominal pain and diarrhea (2−3 times per day). Ten

days before admission, she underwent colonoscopy, but it was difficult

to advance the colonoscope due to secondary intestinal stenosis. Biopsy

and three-dimensional computed tomography of the small intestine

confirmed the diagnosis of CD. Following admission to the hospital, a

series of related examinations were performed. Electrocardiography

revealed a normalized rhythm. Further evaluation revealed the following:

slight leukopenia (leukocytes count, 3.2 × 10 9 / L); serum albumin level,

36.1 g/L (normal range,40−55 g/L); platelet count, 123 × 10 9 / L (normal

range, 125−350 × 10 9 /L); serum calcium level, 2.18 mmol/L (normal

range, 2.25−2.75 mmol/L); fecal calprotectin level, 827.162 µg/g

(normal range 0−50 µg/g) and serum magnesium level, 0.82 mmol/L

(normal range, 0.7−1 mmol/L). T cell spot test for tuberculosis (T-SPOT.

TB) revealed negative findings. She also had no history of alcohol use

or drug abuse. Subsequently, treatment with infliximab was initiated

at a dosage of 5 mg/kg. She did not experience any side effects after

the first infliximab infusion. Two weeks later, she received the second

infliximab infusion (5 mg/kg), but after 5 days, she suddenly developed

short episodes of impairment of consciousness at home along with

limbs twitches and the extroversion of eyeball. During the episode, her

tongue was bitten, and her head was hurt. The episodes lasted for

approximately 3 min, and she was taken to a local hospital for treatment

by her family. However, she was not treated after observation at the

hospital (details unspecified). According to the schedule, the patient

received the third infliximab infusion at a loading dose of 5 mg/kg. She

experienced repeated episodes after 5 days of the third infusion. She was

taken to the local hospital, and craniocerebral CT showed no obvious

abnormalities. She was then admitted to the Department of Neurology

for further evaluation. Laboratory data showed normal findings, except a

high L-cholesterol level (3.35 mmol/L; normal range, 1.89−3.1 mmol/L)

and low lencocyte count (2.7 × 10 9 /L; normal range, 3.5−9.5 × 10 9 /L).

All physical examination findings were unremarkable. On the third day of

admission, she experienced another similar seizure episode. Therefore,

diazepam (5 mg) and sodium valproate(800 mg) were administered

intravenously to control the seizures. No recurrence was observed after

treatment during hospitalization. She underwent a brain 3.0 T magnetic

resonance angiography (MRA), which showed no apparent abnormality.

Video electroencephalography revealed background activity in the alpha

range with an amplitude reduction but a good waveform. On both sides of

the forehead and temporal area, scattered sharp waves were observed;

the waves were more obvious on the right side. During the monitoring

period, the patient was cooperative and did not show any behavioural





Center of Clinical Evaluation, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, Zhejiang, China

Full list of author information is available at the end of the article


Table 1 Summary of patient characteristics, seizures, and outcome

Features of




onset to




Patients Age at



EEG CSF Other Treatment

for the









each lasting

about 1 min

and followed

by several

periods of


tonic clonic


lasting more

than 6 min

Mild excess

slow wave


Focal paroxysmal


Normal MRI revealed


T2 and fluidattenuated



signal hyperintensities

in a broadly



affecting the




poles, medial


lobes, and


frontal lobes

Not recorded MRI showed



mainly cortical






5 days after

the first






1 14, male Crohn’s






Not recorded MRI showed

scattered T2/

FLAIR signal


in the subcortical


matter predominantly

in the frontal

and posterior

parietal lobes




No more



No more



No more



Study author

and year

of publication

Remission for

6 months

and finally



in colectomy

and ileostomy.

Zamvar,2009 [9]

Not recorded Brigo,2011 [10]

Not recorded Chow,2016 [12]

abnormalities. The Electroencephalogram (EEG) confirmed the diagnosis

of seizures and so far we highly suspected that the occurrence of the

seizures may be associated with the use of infliximab. The patient

Impairment of



and arrest

of volitional



and disorientation,


2 days after

the second



2 74, male Crohn’s


Experienced 2

episodes of


tonic clonic


3 days following





3 24, female Crohn’s


started maintenance therapy with valproic acid (500 mg/day) and was

discharged after 6 days. Although there was a clear response to infliximab

with a reduction of diarrhoea and abdominal pain, the infliximab treatment





Table 1 (continued)

Study author

and year

of publication






EEG CSF Other Treatment

for the


Features of




onset to




Patients Age at



Haddock,2011 [11]

was ceased and no seizures occurred after discharge. Now thalidomide

(25 mg/d) was used to maintain remission of CD. The patient was

following up for the moment.

Well controlled,

and no further


at two year

follow up.

Three focal

seizures post







Normal MRI showed


high signal in

the subcortical




lobes, and

on the right

side with

extension to

involve the

right temporal


Right temporal

lobe dysfunction

Nausea, visual



dilated reactive



and hypertensive.

13 days after

the first



4 8, female Crohn’s


TNF, tumor necrosis factor; EEG, electroencephalogram; CSF, cerebrospinal fluid; MRI: magnetic resonance imaging

Discussion and conclusions

Infliximab is a chimeric monoclonal antibody against the soluble and

the membrane tumour necrosis factor (TNF)-α [4]. It is effective in

inducing and maintaining remission in patients with moderate-to-severe

CD refractory to conventional therapy [5]. However, administration of

infliximab is associated with a well-recognized risk of infusion-related

adverse events, such as infusion reactions, autoimmune disorders,

malignancies, opportunistic infections, and serious infections [6]. The

neurological effects of infliximab have also been reported. Headache is

the most commonly reported, occurring in 12–18 % of patients studied

in the clinical trial setting [7]. The other commonly reported events

include peripheral neuropathy [8] and central nervous system and/

or spinal cord demyelination. Most patients have good tolerance to

infliximab; however, with its wide use in various autoinflammatory and

immune diseases, it is expected that more adverse drug reactions will

be reported in the future.

A literature review revealed that infliximab-related seizures have been

rarely reported (Table 1). In 2008, a 14-year-old boy with active CD

experienced probable occipital lobe seizures, followed by several

episodes of generalized tonic clonic seizures, 5 days after the first

infliximab administration [9]. In 2011, Francesco Brigo et al. [10] reported

a case of a 74-year-old man with CD who developed a sudden seizures

2 days after the second infliximab administration. His medical history was

notable for hepatitis C virus cirrhosis with normal liver function and for

an ischemic right temporo-occipital stroke, but he did not have a history

of previous seizures. Electroencephalography showed any paroxysmal

activity. In 2011, Rosemary Haddock et al. [11] reported a case of

posterior reversible encephalopathy syndrome in an 8-year-old girl with

CD after infliximab administration and colectomy. In 2016, Chow et al. [12]

reported a similar case of a 24-year-old woman who developed posterior

reversible encephalopathy syndrome(PRES) after the second treatment

with infliximab. Among the abovementioned, two cases occurred after the

second injection of infliximab, and two occurred after the first injection of

infliximab. There seemed to be no apparent consistency in the time of the

occurrence of the adverse reaction and definitely none of the patients had

a history of previous seizures.

In our case, there was a direct correlation between seizures and

infliximab administration. To the best of our knowledge, this is one of few

case reports of infliximab-induced seizures. In contrast to the previous

cases, our patient experienced the rechallenge events. Five days after

the second infusion, the patient experienced actually a seizure, just

failing to give enough attention. She again experienced seizures after

the third infusion. This positive rechallenge was the strongest proof

of side effects of infliximab. In the absence of infective, metabolic

encephalopathy and other known etiologies, symptoms regressed

quickly and completely. We also ruled out the possibility of seizures

caused by other drugs because no special drugs were administered

before the first three seizures except infliximab. MRA revealed no

abnormalities. Based on the video electroencephalography findings,

we speculated that the seizures were clearly associated with infliximabrelated

neurotoxicity. In previously reported cases, Posterior Reversible

Encephalopathy Syndrome (PRES) has been reported, but in our case,

both clinical symptoms and neuroradiological results were incompatible

with the diagnosis of PRES. Therefore, this case was different from the

other previously reported cases.



The mechanism of infliximab-induced seizures is unclear. However, it

may be due to the systemic pro-inflammatory effects of α-TNF agents

that cause an inflammatory response in the nerves [13]. Therefore,

infliximab should be cautiously administered to patients to minimize

possible morbidity for patients. Medication withdrawal is the first step

in managing patients with suspected drug-induced neuropathy [14],

The adverse events can occur in the initial stage of infliximab treatment

during induction phase. Moreover, all cases reported thus date had

no history of previous seizures and no other plausible cause of the

seizures. Consequently,we must underline the possibility of serious

and unexpected adverse reactions to infliximab, which are rare and

unpredictable. Considering the elimination half-life of infliximab (10

days), we should pay particular attention to the adverse reactions after

infliximab injection, especially before and after the second injection.

Various neurological complications such as demyelination and

peripheral neuropathy after treatment with TNF-α inhibitors have been

reported [14, 15]. For patients with a history of demyelination, seizures

or other serious neurological disorders, the use of TNF-α inhibitors

may increase the risk of exacerbation of neurological symptoms.

Neurological assessment and tight clinical monitoring before and

during therapy with infliximab should be performed in patients with

pre-existing seizure disorders. If absolutely necessary, prior assessment

and appropriate measures should be still taken before initiating therapy.

Further studies are still needed to evaluate the exact relationship

between infliximab and seizures.


CD: Crohn’s disease; IBD: inflammatory bowel disease; TNF-α: Tumor

necrosis factor-alpha; MRI: Magnetic resonance imaging; MRA:

Magnetic Resonance Angiography; EEG: Electroencephalogram; CT:

Computed tomography; PRES: Posterior Reversible Encephalopathy



All authors thank the patient for her support.

Authors’ contributions

LZJ performed the literature review. ZXQ collected the clinical data. WL

prepared the first version of the manuscript. All authors participated

in further drafting and revision of the manuscript. All authors read and

approved the final manuscript.


This research was funded by Health Commission of Zhejiang Province

(No.2020KY201) and Zhejiang Chinese Medical University (No.KC201936).

The funding bodies had no role in the design of the study and collection,

analysis, and interpretation of data and in writing the manuscript.

Availability of data and materials

This case report contains clinical data from the electronic medical record

in the Nanjing Drum Tower Hospital. The datasets used during the current

study are available from the corresponding author on reasonable request.


Ethics approval and consent to participate

Authors’ institution does not require ethical approval for publication of

a single case report. Written informed consent was obtained from the


Consent for publication

Written informed consent was obtained from the patient for publication

of this case report and the accompanying images.

Competing interests

The authors declare that they have no competing interests.

Author details


Department of Pharmacy, Sir Run Run Shaw Hospital, School of

Medicine, Zhejiang University, 3 Qingchun Road, Hangzhou 310006,

Zhejiang, China. 2 Department of gastroenterology, Nanjing Drum Tower

Hospital, The Affiliated Hospital of Nanjing University Medical School,

321 Zhongshan Road, Nanjing 210008, Jiangsu, China. 3 Center of

Clinical Evaluation, The First Affiliated Hospital of Zhejiang Chinese

Medical University, 54 Youdian Road, Hangzhou 310006, Zhejiang,


Received: 30 November 2020 Accepted: 20 April 2021

Published online: 27 April 2021


1. Khanna D, McMahon M, Furst DE. Safety of tumour necrosis factor-alpha

antagonists. Drug Saf. 2004;27(5):307–24.

2. Melsheimer R, Geldhof A, Apaolaza I, Schaible T. Remicade ® (infliximab): 20

years of contributions to science and medicine. Biologics. 2019;13:139 – 78.

3. Aubin F, Carbonnel F, Wendling D. The complexity of adverse side-effects to

biological agents. J Crohns Colitis. 2013;7(4):257–62.

4. Bramuzzo M, Arrigo S, Romano C, et al. Efficacy and safety of infliximab in very

early onset inflammatory bowel disease: a national comparative retrospective

study. Unit Eur Gastroenterol J. 2019;7(6):759–66.

5. Zaltman C, Amarante H, Brenner MM, et al. Crohn’s disease-treatment with

biological medication. Rev Assoc Med Bras. 2019;65(4):554–67.

6. Wang X, Cao J, Wang H. Risk factors associated with Infusion Reactions to

Infliximab in Chinese Patients with Inflammatory Bowel Disease: A Large Single-

Center Study. Med Sci Monit. 2019;25:2257–64.

7. Gill C, Rouse S, Jacobson RD. Neurological complications of therapeutic

monoclonal antibodies: trends from oncology to rheumatology. Curr Neurol

Neurosci Rep. 2017;17(10):75.

8. Shivaji UN, Sharratt CL, Thomas T, et al. Review article: managing the adverse

events caused by anti-TNF therapy in inflammatory bowel disease. Aliment

Pharmacol Ther. 2019;49(6):664–80.

9. Zamvar V, Sugarman ID, Tawfik RF, Macmullen-Price J, Puntis JW. Posterior

reversible encephalopathy syndrome following infliximab infusion. J Pediatr

Gastroenterol Nut. 2009;48(1):102–5.

10. Francesco Brigo 1, Luigi Giuseppe Bongiovanni. et al. Infliximab-related seizures:

a first case study. Epileptic Disord. 2011;13(2):214–7.

11. Haddock R, Garrick V, Horrocks I, Russell RK. A case of posterior reversible

encephalopathy syndrome in a child with Crohn’s disease treated with infliximab. J

Crohns Colitis. 2011;5(6):623–7.

12. Chow S, Patnana S, Gupta NK. Posterior reversible encephalopathy syndrome in a

patient with Crohn’s disease on infliximab. J Clin Gastroenterol. 2016;50(8):687.

13. Tsouni P, Bill O, Truffert A, Liaudat C, Ochsner F, Steck AJ, et al. Anti-TNF alpha

medications and neuropathy. J Peripher Nerv Syst. 2015;20(4):397–402.

14. Stübgen JP. Tumor necrosis factor-alpha antagonists and neuropathy. Muscle

Nerve. 2008;37(3):281–92.

15. Deepak P, Stobaugh DJ, Sherid M, Sifuentes H, Ehrenpreis ED. Neurological

events with tumour necrosis factor alpha inhibitors reported to the Food and

Drug Administration A dverse Event Reporting System. Aliment Pharmacol Ther.





National Report shows

Crohn’s and Colitis healthcare

urgently needs improvement

• Evidence from over 10,000 people with Crohn’s

or Colitis and 72% of specialist IBD health

services reveals that care across the UK is

costing some patients their health and the NHS

millions in unnecessary emergency treatment.

• COVID-19 has made worse issues such

as delays in diagnosis, long waits for

investigations and surgery, and little access

to much needed psychological and dietetic


• Crohn’s & Colitis UK, the UK’s leading

charity for Crohn’s and Colitis, as part of

IBD UK, is calling for more resources and

support for services to deliver better care

for the half a million people living with this

complex condition.

• IBD must be recognised as an NHS priority

with a clear government strategy in all four

nations over the next 5 years.

A new report from IBD UK – a coalition of

leading health specialists in Crohn’s and

Colitis care, including charities, 17 professional

organisations and Royal Colleges - reveals

a UK-wide picture of IBD care which was

already stark prior to the COVID-19 pandemic.

The ‘Crohn’s and Colitis Care in the UK: The

Hidden Cost and a Vision for Change’ report 1

is the most comprehensive assessment of UK

care ever undertaken in the UK.

Sarah Sleet, CEO at Crohn’s & Colitis UK

and Chair of IBD UK summarises the current

state of play: “Crohn’s and Colitis are serious

conditions which aren’t taken seriously.

Unacceptably high levels of emergency

care and delays to diagnosis, investigations,

and surgery, exacerbated by the COVID-19

pandemic, are signs of services under

pressure and a model of care which is not

working. The report sets out a vision for

change – this needs to be prioritised by

governments across the UK and supported

with a defined long-term strategy.”

Diagnosis is taking too long

The report found that it is taking too long

for people with Crohn’s and Colitis to be

diagnosed, delaying their treatment and

support and resulting in potentially avoidable

flares and emergency care. Of over 10,000

people responding to the survey, a quarter

(26%) waited over a year for their diagnosis,

41% visited A&E at least once before

diagnosis, and 12% visited three times. For

everyone with Crohn’s and Colitis, almost three

quarters (72%) of admissions to hospital were

an emergency. This should not be the norm

for people with IBD. Not only does this have a

human health impact, but it is incredibly costly

to the NHS as the report showed that the cost

of managing someone in a flare is up to 6

times higher than when they are in remission.

Jacob is 19 years-old and lives with Crohn’s.

“Over 1–2 years before I was diagnosed, I

went to the GP several times. My diagnosis

was sudden and scary. At 4am one morning, I

was in terrible pain and couldn’t move an inch.

I felt like something inside was going to pop,

so an ambulance was called. I had a CT scan

which showed that my bowel was perforated

and I had contracted sepsis. I needed

emergency surgery, which resulted in a stoma

being formed to allow my bowel to rest... It had

a big impact on my mental health.”

Effects outside the gut are overlooked

Once diagnosed, care for people with Crohn’s

and Colitis is not proactive and is focused on

medication, rather than the wider impact of

the conditions. People are often left struggling

with severe pain, extreme fatigue, anxiety, and

problems outside the gut, with 89% of people

reporting they found it hard cope with having

Crohn’s or Colitis over the previous year.

Moreover, only 1 in 10 people (10%) said they



Gastroenterology Today welcomes the submission of

clinical papers and case reports or news that

you feel will be of interest to your colleagues.

Material submitted will be seen by those working within all

UK gastroenterology departments and endoscopy units.

All submissions should be forwarded to

If you have any queries please contact the publisher Terry Gardner via:



were assessed for how they had been coping

emotionally. Left unchecked and unchallenged,

we risk losing the potential of more future

generations of young people with IBD unable

to live fulfilling, productive lives.

People do not have access to a full range

specialist care

The report also found that people do not have

access to the full range of specialist care they

need. Most services are falling far short of

meeting the IBD Standards 2 recommendations

for crucial roles, including IBD nurse

specialists, dietitians, and psychologists. Less

than half (48%) of people felt their care was

coordinated with other specialist services.

The effects of Covid-19

Covid-19 has exacerbated issues which were

already stark prior to the pandemic, such as

delays in diagnosis, long waits for elective

care, surgery, and investigations, and little

access to multi-disciplinary teams. The report

shows that people with IBD cannot be left

behind as services rebuild post-Covid.

A vision for change

This coalition of experts in IBD care, wants

political decision makers across the four

nations to ensure that IBD is recognised as an

NHS priority with a clear government strategy

over the next 5 years.

In response to the findings from the report, Dr Ian

Arnott, IBD Section Chair at the British Society

of Gastroenterology says: “Despite fantastic

work to improve IBD care over the last couple of

decades, it’s clear that something fundamental

needs to change to deliver care that is more

personalised, preventative and proactive. It’s

time that IBD was recognised as the serious

condition it is, with appropriate prioritisation

and support provided to enable significant

improvements to be made across all services.

This comes at a pivotal moment as services

reconfigure in response to the COVID-19

pandemic. We can and we must do more to

ensure people with IBD receive safe, consistent,

high-quality, personalised care whatever their

age and wherever they live in the UK.”


1. IBD UK, ‘Crohn’s and Colitis Care in the UK:

The Hidden Cost and a Vision for Change’,


2. IBD Standards, IBD UK, 2019.

Coeliac UK poll highlights

concerns when eating out

post lockdown

• 36% of people said their biggest concern

was being an inconvenience 1

• Nearly half of people (48%) are worried

about being ‘glutened’ when eating at family

or friends 1

• 60% said they were less confident –

compared to before the lockdown – in

finding gluten free venues 2

In a recent poll by Coeliac UK, the national

charity for people with coeliac disease and

those who need to live without gluten, over a

third (36%) of people responding, said their

biggest concern when eating at a friend or

family’s house post lockdown, was about

being an inconvenience 1 .

Nearly half (48%) were most worried about

being accidentally ‘glutened’. A term used

by people diagnosed with coeliac disease

when they eat food that contains, or is crosscontaminated

with, gluten; a protein found in

wheat, barley or rye.

In another poll 2 nearly 60% of people said they

were less confident - compared to before the

pandemic - in finding gluten free venues post


Coeliac UK, aims to #ShineALightOnCoeliac in

a campaign running from 10-16 May 2021. The

campaign is focussing on the needs of children

and young people, by providing resources, tips,

recipes and advice for people when they are

eating away from home, which can be shared

with those catering for them, and in addition the

charity has launched a fundraising challenge to

raise £50,000 to support children with coeliac

disease in the future.

Hilary Croft, Coeliac UK CEO said: “Trusting

other people to provide gluten free food can

cause major feelings of anxiety and lead to

people avoiding social events. The last thing

anyone, let alone a young person needs now

is more isolation. So we are aiming to shine a

light on coeliac disease to make life better for

everyone who needs to live gluten free.”

Coeliac disease is not an allergy or an

intolerance but an autoimmune disease where

the body’s immune system damages the lining

of the gut when gluten is eaten. There is no

cure and no medication; the only treatment is

a strict gluten free diet. People diagnosed with

coeliac disease must maintain a strict gluten

free diet for the rest of their lives to reduce

the risk of very serious complications such

as osteoporosis, infertility and although rare,

small bowel cancer.

“As more people venture back out to eat at

their favourite restaurants, the poll results show

a worrying majority who are now less confident

about finding venues that offer safe gluten free

food. Before the pandemic, social distancing

and lockdowns there were venues across the

UK, accredited by Coeliac UK, serving safe

gluten free menu options. However, as we

know the hospitality industry has been severely

impacted by the pandemic, and we have

unfortunately seen closures and suspensions

of gluten free menus as the sector tried to

survive and weather the storm.”

“As lockdown eases, we are strongly

supporting our accredited partners to help

them continue to provide safe gluten free

options. Over the coming weeks and months,

we are preparing to shine a light on places

you can visit again, confident in the knowledge

of their commitment. And in the meantime,

to assist the community when eating out, we

have produced a handy pocket checklist of

things to ask venues both before and when

you visit them,” continued Ms Croft.

Coeliac UK’s Gluten Free Accreditation

programme provides customers with

assurance that they can enjoy safe gluten free

options and identify venues, which follow strict

procedures in food handling and ingredient

use, to ensure a safe gluten free experience.

1 in 100 people in the UK is estimated to

have coeliac disease but of these, only 30%

are currently diagnosed, meaning there are

nearly half a million people in the UK with

undiagnosed coeliac disease.

For more information about Coeliac UK

Awareness Week and the Challenge Week,

please see:





EoS Network launches

ground breaking online

educational series for

patients, clinicians & the

general public

‘An urgent need to raise awareness of this

poorly understood condition’

To mark National Eosinophilic Awareness

Week, the charity EoS Network launched a

series of publicly available webinars to shed

light on Eosinophilic Gastrointestinal Disease

(EGID), an underdiagnosed set of chronic

conditions which affect the oesophagus and/or

lower gut and creates lifelong difficulties with

swallowing, eating and digestion.

Eosinophilic Diseases are immune-mediated,

most probably caused by food allergies or

other environmental triggers which occurs

in the upper gut (Eosinophilic Oesophagitis)

and/or the lower gut (Eosinophilic Gastritis,

Eosinophilic Gastroenteritis, Eosinophilic


In the most common of these conditions,

Eosinophilic Oesophagitis (EoE) this

immune response results in inflammation

of the mucosa in the oesophagus which,

if left untreated, can lead to oesophageal

remodelling including the formation of

strictures or furrows. In turn this creates

difficulties with swallowing certain foods or

tablets including food sticking or even food

obstructions. (SEE NOTES). In the UK it is the

single most common reason for emergency

admission to A&E for food bolus (obstructions)

removal. 1

Patients with EoE report living with constant

fear of choking, often avoid ‘tough’ ‘chewy’

foods and are embarrassed to eat with others

or in public due to coughing fits and/or

retching when food sticks. They often develop

avoidance tactics such as eating with lots of

water or eating very slowly. As a consequence,

understandably some develop anxiety around

eating and socialising.

Often misdiagnosed as GORD (gastrooesophageal

reflux disease) 2 or heartburn,

many sufferers go undiagnosed due to lack

of clinical and general awareness. Research

has found that the average time to receive a

diagnosis is around eight years 3

‘As a relatively newly recognised disease,

it is extremely important that we improve

eosinophilic gastrointestinal disease

awareness amongst the public, patients and

healthcare professionals,’ says Amanda

Cordell, CEO of the EoS Network. ‘These

webinars provide a valuable resource for

all these groups and feedback has been

extremely positive not only for patients but

also Health Care Practitioners (HCPs) who are

eager to learn more about this disease.’

The series of webinars, which have been

supported by the National Lottery Community

Fund in conjunction with government Covid

19 funding, are led by experts from across

the field of gastroenterology, dietetics and

allergy. They provide a complete overview of

Eosinophilic Oesophagitis, covering topics

such as the role of allergy in EoE, emergency

issues, long term management and dietary

solutions, along with information on paediatric

care and on the more complex EGIDs. They

will go live on the EoS Network website during

the Awareness Week and will be available for

anyone to access at

‘Along with these webinars, we also provide

educational tools, support and other resources

via our educational hub,’ explains Amanda. ‘In



Gastroenterology Today welcomes the submission of

clinical papers and case reports or news that

you feel will be of interest to your colleagues.

Material submitted will be seen by those working within all

UK gastroenterology departments and endoscopy units.

All submissions should be forwarded to

If you have any queries please contact the publisher Terry Gardner via:



addition, we host a dedicated network section

for registered healthcare professionals from

around the world, allowing them to exchange

advice, research and support on treating these

unpleasant and life changing conditions.’

‘EoE is a chronic disease that, if left untreated,

can cause a severe food obstruction requiring

emergency medical removal. If you are having

the symptoms, we describe on our website

then you should discuss them with your GP

without delay.’

‘In the meantime, vital research continues into

the rarer, more complex lower gut eosinophilic

diseases which are severely life impacting,

an area where currently patients remain

desperate for emerging clinical guidelines and

treatments.’ 6

For more information or to interview

Amanda Cordell, please contact Graeme

Whitcroft at Healthy PR on 07793980500 or

About the EoS network charity

The EoS Network works to ensure that every

person with an Eosinophilic Gastrointestinal

Disease receives a prompt accurate diagnosis,

the right treatment for them and support

to live with their condition. Its vision is for a

world where everyone with an Eosinophilic

Gastrointestinal Disease can eat without pain.

The EoS Network provides information and

support for patients and their families, a

global platform for clinicians and researchers,

educational resources and events and works

with medical bodies, manufacturers and

funders to ensure that the patient’s voice is


Notes on EoE

EoE is clinically characterized by oesophageal

dysfunction and histologically characterized by

an eosinophil-rich inflammation, most probably

caused by common food allergies or other

environmental triggers. Often misdiagnosed as

GORD, 2 adult symptoms include dysphagia,

bolus obstruction and chest pain related

to swallowing, heartburn and regurgitation.

In children they can include reflux-related

symptoms, nausea, vomiting, abdominal pain,

refusal to eat or failure to grow. 2 Untreated

EoE can lead to oesophageal remodelling

including the formation of strictures and EoE is

the cause of more than 50% of all emergency

presentations for oesophageal food bolus Current clinical guidelines can be found @

impactions. 1

Annual incidence rates of EoE in western

countries are 10 per 100,000 with prevalence References

rates of 86 per 100,000. 4 However, for patients

with oesophageal symptoms who undergo 1. Prevalence of eosinophilic oesophagitis in

gastroscopy the prevalence is 7% whilst in

adults presenting with oesophageal food

patients with dysphagia and bolus obstruction, bolus obstruction. World J Gastrointest

prevalence increases to 23-50%. 1 Many

Pharmacol Ther 2015;6:244–247.

patients have a history of atopy, particularly Heerasing N, Lee SY, Alexander S, et al

asthma, allergic rhinitis and eczema. 5

2. Eosinophilic esophagitis N Engl J Med.

2015;373(17):1640–8. Furuta GT, Katzka

EoE only received classification in the 1990s DA.

and disease awareness, amongst both

3. Gastrointest Pharmacol Ther 2016; 7(2):

clinicians and the general public, is thought to 207-13. Ahmed M. World J

be low. Currently, average time to diagnosis 4. Limketkai BN et al Gut 2019 ; 68 : 2152-

is up to 8.1 years. 2 Due to the patchy nature 2160

of the disease, diagnosis requires 6 biopsies 5. Aliment Pharmacol Ther 2016; 43(1): 3-15.

to be taken from around the oesophagus

Arias Á et al

via endoscopy. Diagnosis is defined by 6. Eosinophilic gastrointestinal diseases

histological presence of eosinophils ≥15hpf. below the belt

jaci.2019.10.013 https://www.jacionline.

Treatment for EoE is focused around three


areas: dietary exclusion, drugs and dilatation. Pesek RD Rothernberg ME

Dietary exclusion is generally considered hard

to maintain and costly. Dilatation, ScheBo_GastroToday_Aug_2020 carried out Registered Multi-Ad_Address_Change

Charity 1143267

when the disease

has progressed

to oesophageal

strictures, is an

invasive procedure

which manages the

symptoms but not

the cause of EoE

and often has to be


Until recently, all

drug treatments

were off-label and

topical steroid

therapy was not

optimised for delivery

to the oesophagus.

However, NICE

and the SMC have

now recommended


orodispersible tablet

(Jorveza ®) for

active EoE in adults,

a treatment option

designed to reach the

area of inflammation

in the oesophagus

(final NICE guidance

due 23rdJune).






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A recent study published by the research group of Professor

Francesco Di Mario at Parma University, Italy, found a strong

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1. Di Mario F, Crafa P, Franceschi M, et al. Low Levels of Gastrin 17 are Related

with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD. JGLD

[Internet]. 12Feb.2021 [cited 11May2021];30(1):25-9. Available from:






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If you have any queries please contact the publisher Terry Gardner via:



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