Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: an ECCO CONFER Multicentre Case Series

Abstract

Background

Hereditary colorectal cancer syndromes [HCCS] are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer [CRC]. Coexisting inflammatory bowel disease [IBD], including ulcerative colitis [UC] and Crohn’s disease [CD], with HCCS is exceedingly rare and presumably increases the risk of early-onset CRC.

Methods

This was a multicentre case series performed as a part of the European Crohn’s and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project.

Results

This report includes 26 patients with IBD (10 UC, 15 CD, and one with IBD unclassified [IBD-U]) and concomitant HCCS. Among these 26 patients([median age 33 years, interquartile range [IQR] 20–44], 15 [57.7%] were males, 24 [92.3%] Caucasians, and two [7.7%] of Arab origin. HCCS was diagnosed before the IBD diagnosis in 11 patients [42.3%], after diagnosis of IBD in 11 patients [42.3%], and concurrently in four patients [15.4%]. Sixteen patients had Lynch syndrome, seven had familial adenomatous polyposis [FAP], two had MYH-associated polyposis [MAP], and one had attenuated FAP [AFAP]. The most frequent genetic mutations were those of APC [n = 7] and MLH1 [n = 7]. Overall, CRC developed in 38.5% of patients [n = 10]: in four patients [40%] after IBD diagnosis, in four [40%] patients before IBD diagnosis, and in two patients the two conditions were diagnosed simultaneously. Eighteen [69.2%] patients underwent colectomy or abdominal surgery: nine patients due to CRC diagnosis, five patients preventively due to the underlying HCCS, three due to the underlying HCCS and concomitant active IBD disease, and one patient because of active IBD disease. One patient died due to CRC.

Conclusions

To date, this is the largest case series of patients with IBD and HCCS. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome. These data demonstrate the high malignancy rate and surgical intervention rate in this IBD cohort, despite the endoscopic surveillance. The optimal medical approach still needs to be addressed.

Crohn’s disease, ulcerative colitis, inflammatory bowel disease, hereditary colorectal cancer syndromes, colorectal cancer

1. Introduction

Inflammatory bowel diseases [IBD], including ulcerative colitis [UC] and Crohn’s disease [CD], are chronic remitting and relapsing diseases, with a significant impact on quality of life and social functioning, as well as psychological health.^1–3 The pathogenesis is partially understood, but it has been hypothesised that it arises from dysregulation of the innate and adaptive immune systems,⁴ leading to an abnormal inflammatory response to commensal bacteria in a genetically susceptible individual.⁵

Patients with IBD are 2–6 times more likely to develop colorectal cancer [CRC] than the general population.⁶ Furthermore, when cancer develops, IBD-CRC patients are affected at a younger age than sporadic CRC patients.⁷ Several known variables affect the risk of IBD-CRC: age at diagnosis and disease duration, extent of mucosal in inflammation and portion of the bowel affected, penetrating disease in CD patients, concomitant primary sclerosing cholangitis, immunosuppressive therapy, family and personal history of CRC, and geographical location.⁸ Regarding the latter, geographical differences may be driven by differences in genetics, diet, chemoprevention, and colonoscopy surveillance.⁸

The two most important high-risk conditions for CRC are IBD and the hereditary colorectal cancer syndromes [HCCS] including hereditary syndromes of familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer syndromes [HNCCS].⁹ Many individuals with HCCS remain unrecognised until the time of a cancer diagnosis, whereas others are identified through genetic testing based on family history of cancer.¹⁰ Coexisting IBD with HCCS is exceedingly rare and presumably may increase the risk of early-onset CRC.¹⁰ However in the scientific literature, the overlap of these two conditions is sparsely reported, with just a few case reports identified.^11–16

In this collaborative case series, we aimed to describe a series of patients with IBD and HCCS, trying to delineate the association between the two conditions, their association with CRC, and patient outcomes.

2. Methods

2.1. Study design

This European Crohn’s and Colitis Organisation [ECCO] observational, multicentre study retrospectively collected cases through the CONFER project. The CONFER project was initiated by ECCO in order to specifically identify and report together rare IBD disease associations, which otherwise are seldom reported due to their exceptional rarity. Once a specific topic was selected by the Steering Committee as a CONFER project, ECCO launched a call to identify similar cases encountered by IBD physicians worldwide. The call to physicians was made through announcements at the ECCO Annual Congress and in national and international IBD meetings across Europe. Furthermore, the call for similar cases was disseminated by direct emails to all ECCO members and affiliated physicians and on the ECCO website and eNews. Physicians were then prompted to report their case to the CONFER database using pre-determined standardised Case Reporting Forms [CRF]. The call for the present case series was entitled ‘Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases’.

2.2. Patients and procedures

Adult patients suffering from HCCS with concomitant IBD were eligible for inclusion in this project. The CRF was divided into two sections. Section 1 included patient [epidemiological data, past medical history, smoking, family history] and IBD characteristics [date of diagnosis, Montreal classification, extraintestinal manifestations, prior surgery for IBD, and treatments]. Section 2 included a description of HCCS: date of diagnosis, type of diagnosis, type of genetic mutations, timing of the event [before, simultaneously with, or after the IBD diagnosis], family history, extracolonic features, IBD disease activity [clinically, biochemically, endoscopically, and radiologically] at the time of HCCS diagnosis, when the immunomodulatory therapy was prescribed and at the time of the latest follow-up visit, date of CRC diagnosis and timing [before, simultaneously with, or after the IBD diagnosis], family history of CRC, date and type of colectomy or abdominal surgery, IBD treatments after HCCS diagnosis, adverse events during treatments, diagnosis of cancers during treatments, and timing of colonoscopy/radiological surveillance. Data were collected and analysed anonymously and handled according to local regulations.

2.3. Statistics

All statistical analyses [descriptive statistics] were performed with SPSS 20.0 software package [IBM SPSS Statistics, Armonk, NJ, USA].

3. Results

From 13 different centres, 26 patients with IBD (10 with UC, 15 with CD, and one with IBD unclassified [IBD-U]) and concomitant HCCS were recruited. Main characteristics of all the included patients are reported in Table 1. The patient median age was 47 years (interquartile range [IQR] 35–55), with 57.7% [n = 15] of patients being males. The majority [92.3%; n = 24] were of Caucasian origin and two [7.7%] were Arabs, from six different countries [Belgium, Italy, France, Israel, Germany, Malta]. The demographic and clinical characteristic,s IBD-, HCCS- or CRC-related, are reported in Table 2. For completeness, we report two out of 26 family trees in Supplementary Figure 1.

Table 1.

Main characteristics of all the included patients.

N.	Country	Sex	Age	1st diagnosis	2nd diagnosis	3th diagnosis	IBD type and Montreal Classification	Treatments before HCCS	Treatments after HCCS	Treatments at the latest follow-up	HCCS type	Genetic mutation	Surgery	Indication for surgery
1	Belgium	M	40	HCCS	CRC	IBD	CD L1, B1	-	5-ASA, Steroids Infliximab	Infliximab	FAP	APC	IPAA	CRC
2	Belgium	F	35	IBD	HCCS	-	CD L3 + L4, B1, perianal disease	5-ASA, steroids, azathioprine, methotrexate, infliximab	5-ASA, infliximab	-	Lynch	MSH2	-	-
3	Belgium	F	50	IBD	HCCS	-	CD L1, B2, perianal disease	Steroids, azathioprine	Azathioprine infliximab	Infliximab	FAP	APC	Ileorectal anastomosis	FAP
4	Belgium	F	66	HCCS	CRC	IBD	CD L1, B1	-	Azathioprine, infliximab	Azathioprine	Lynch	MSH2	Sigmoid resection	CRC
5	Belgium	M	31	HCCS	IBD	-	CD L1, B3, perianal disease	-	Steroids, azathioprine and infliximab [combination therapy]	-	FAP	APC	Ileostomy	FAP
6	Belgium	M	44	IBD	HCCS	-	UC E3	5-ASA	5-ASA steroids, azathioprine and infliximab [combination therapy]	5-ASA Azathioprine and infliximab [combination therapy]	Lynch	PMS2	-	-
7	Belgium	M	63	HCCS	IBD	-	UC E1	-	5-ASA	5-ASA	Lynch	MLH1	-	-
8	Belgium	M	38	HCCS	IBD	-	UC E1	-	5-ASA	5-ASA	Lynch	MSH2	-	-
9	Belgium	M	55	IBD	HCCS	-	UC E2	5-ASA, ciclosporin, azathioprine	5-ASA, azathioprine	5-ASA, azathioprine	Lynch	-	-	-
10	Belgium	F	49	IBD	HCCS	-	IBD-U pancolitis	5-ASA, steroids, azathioprine, methotrexate, infliximab	5-ASA	5-ASA	Lynch	MLH1	-	-
11	Belgium	F	28	IBD	HCCS	CRC	CD L1, B2	Azathioprine, infliximab, vedolizumab	Vedolizumab	Vedolizumab	Lynch	MSH2	IPAA	CRC
12	Italy	M	49	IBD	HCCS	CRC	UC E1	5-ASA steroids	5-ASA steroids	-	Lynch	MSH2	Ileostomy	CRC
13	Italy	F	59	IBD	HCCS	CRC	UC E2	5-ASA	5-ASA	-	Lynch	MSH2	Ileostomy	CRC
14	Italy	M	47	HCCS	CRC	IBD	CD L3, B1,	-	5-ASA	-	Lynch	MLH1	Ileostomy	CRC
15	Italy	F	58	HCCS	IBD	-	CD L1, B1	-	Steroids Infliximab, adalimumab	-	FAP	APC	IPAA	FAP
16	Italy	M	56	HCCS	CRC	IBD	CD L3, B1	-	5-ASA teroids	5-ASA	Lynch	MLH1	Left hemi-colectomy	CRC
17	Italy	M	24	IBD and HCCS	-	-	UC E3	-	5-ASA steroids methotrexate infliximab adalimumab	Methotrexate and infliximab [combination therapy]	Lynch	MLH1	IPAA	Active disease
18	Italy	F	34	HCCS	IBD	-	UC E1	5-ASA steroids	5-ASA steroids	5-ASA	Lynch	MLH1	-	-
19	Italy	M	21	IBD	HCCS and CRC	-	UC E3	5-ASA	5-ASA Infliximab	Infliximab	Lynch	MLH1	IPAA	CRC
20	Italy	M	19	IBD and HCCS	-	-	CD L3, B1	-	Infliximab ustekinumab	Ustekinumab	AFAP	APC	Ileorectal anastomosis	AFAP and active disease
21	France	M	51	HCCS	IBD	-	CD L1, B2	-	Steroids methotrexate infliximab adalimumab certolizumab secukinumaba upadacitinib	Upadacitinib	FAP	APC	IPAA	FAP and active disease
22	France	M	50	IBD, HCCS, and CRC	-	-	CD L3, B3, perianal disease	-	5-ASA adalimumab	-	FAP	APC	Ileostomy	CRC
23	Israel	F	64	IBD	HCCS	-	CD L2, B1	5-ASA	-	-	MAP	MYH	Ileorectal anastomosis	Multiple polyps
24	Israel	F	44	IBD	HCCS	-	CD L2, B3 Perianal disease	Steroids azathioprine Infliximab adalimumab certolizumab vedolizumab ustekinumab tacrolimus	-	-	MAP	MYH	Proctectomy for IBD and then ileostomy for IBD and HCCS	Severe disease and MAP
25	Germany	F	47	HCCS	IBD	-	CD L1, B3 Perianal disease	-	Azathioprine 6-mercaptopurine infliximab adalimumab ustekinumab	Ustekinumab	FAP	-	IPAA	FAP
26	Malta	M	35	IBD, HCCS and CRC with metastasis	-	-	UC E2	-	5-ASA	-	Lynch	MSH6	-	-

AFAP, attenuated familial adenomatous polyposis; 5-ASA, 5-aminosalicylic acid; CD, Crohn’s disease; CRC, colorectal cancer; F, female; FAP, familial adenomatous polyposis; HCCS, Hereditary Colorectal Cancer Syndromes; IBD-U, Inflammatory Bowel Disease unclassified; IPAA, Ileal pouch-anal anastomosis; IQR, interquartile range; MAP, MYH associated polyposis; UC, ulcerative colitis; M, male; Montreal classification for CD: L1: ileal; L2: colonic; L3: ileocolonic; L4: isolated upper disease; B1: non-stricturing, non-penetrating; B2: stricturing; B3: penetrating; Montreal classification for UC: E1: proctitis; E2: left-sided colitis; E3: extensive UC.

Secukinumab was prescribed for a concomitant diagnosis of ankylosing spondylitis.

Table 2.

Patients’ demographic and clinical characteristics IBD-, HCCS- and CRC-related.

Characteristics	Total [n = 26]
Age [median, IQR], years	47, 35–55
Sex, n [%]
Male	15 [57.7]
Female	11 [42.3]
Ethnicity
Caucasian	24 [92.3]
Arab	2 [7.7]
Black	-
Geographical spread, n [%]
Belgium	11 [42.3]
Italy	9 [34.7]
France	2 [7.6]
Israel	2 [7.6]
Germany	1 [3.9]
Malta	1 [3.9]
Smoking: current/never/former/unknown, n [%]	8 [30.8]/ 15 [57.7]/ 2 [7.7]/ 1 [3.8]
Alcohol use
Yes	7 [26.9]
No	16 [61.5]
Unknown	3 [11.6]
Age when IBD features appear [median, IQR], years	33, 20–44
Family history of IBD, n [%]	2 [7.7]
Patients with extraintestinal manifestations, n [%]	4 [15.4]
Prior surgery for IBD, n [%]a	4[15.4]
Age at HCCS diagnosis [median, IQR]	31, 21–41
Family history of HCCS, n [%]	23 [88.5]
Extracolonic features, n
Gastric polyps	6
Duodenal adenoma	5
Small bowel adenomas	1
Desmoid tumours	-
Osteomas	-
Medulloblastoma	-
Thyroid involvement	1
Othersb	2
Malignancy	-
Age at colorectal cancer diagnosis [median, IQR]	35, 24–44
Diagnosis of CRC, n [%]	10 [38.5]
Patients with Lynch syndrome	8 [80.0]
Patients with FAP	2 [20.0]
Family history of CRC, n [%]	6 [23.1]

CRC, colorectal cancer; FAP, familial adenomatous polyposis; HCCS, hereditary colorectal cancer syndromes; IBD, inflammatory bowel disease; IQR, interquartile range.

Surgery for IBD before HCCS or CRC diagnosis.

Adrenal adenoma, gall bladder polyps.

3.1. IBD characteristics

The median age at the time of IBD diagnosis was 33 years [IQR 20–44], and only two patients [7.7%] had a family history of IBD [Table 2].

Among patients with UC, four [40%] had proctitis, three [30%] patients had left-sided colitis, and the rest [n = 3; 30%] had pancolitis; whereas among patients with CD, eight [53.3%] had ileal, five [33.3%] had ileocolonic, and two [13.3%] patients had colonic disease. One of the patients with ileocolonic disease had upper gastrointestinal tract involvement. Six patients [40%] had associated perianal disease. Many of patients with CD had a non-stricturing, non-penetrating phenotype [53.3%, n = 8], 20.0% [n = 3] had stricturing disease, and 26.7% [n = 4] had a penetrating phenotype, respectively. Four patients [15.4%] underwent surgery for active and severe IBD disease [three CD and one UC, among whom one underwent ileorectal anastomosis, one underwent ileostomy and two underwent proctocolectomies with ileal pouch-anal anastomosis] [Table 1].

3.2. HCCS characteristics

The median age at the time of HCCS diagnosis was 31 years [IQR 21–41], and 23 [88.5%] patients had a known family history of HCCS [Table 2]. HCCS was diagnosed before the IBD diagnosis in 11 patients [42.3%], after diagnosis of IBD in 11 patients [42.3%], and concurrently in four patients [15.4%]. Sixteen patients had Lynch syndrome, seven had FAP, two had MYH-associated polyposis [MAP], and one had attenuated FAP [AFAP]. Genetic tests were available for 24 patients [92.3%] and the most frequent genetic mutations were those of APC [n = 7] and MLH1 [n = 7], the rest of patients having MSH2 [n = 6], MYH [n = 2], and other minor [n = 2] mutations. Overall, 17 [65.4%] patients were receiving immunomodulatory therapy. In 11 patients, these were prescribed only after HCCS diagnosis and in six patients prior to HCCS diagnosis. At the latest follow-up, 11 patients were still receiving immunomodulatory treatments [Table 1].

Overall, during therapy four patients developed drug-induced side effects: one patient developed skin allergic reaction during treatment with infliximab, which did not require drug interruption; one patient had both the infliximab and 6-mercaptopurine stopped [patient developed peripheral polyneuropathy, nausea, vomiting, and upper abdominal pain]; one patient had to stop adalimumab for paradoxical psoriasis; one patient interrupted infliximab for allergic reaction. Moreover, one patient treated with vedolizumab developed CRC, despite yearly colonoscopy surveillance, after 4 years of treatment.

3.3. CRC characteristics

The median age at the time of CRC diagnosis was 35 years [IQR 24–44] [Table 2]. Overall, CRC developed in 38.5% of patients [n = 10]: in four patients [40%] after IBD diagnosis [median 7.5 years, IQR 3.5–11.5], in 4 [40%] patients before IBD diagnosis [median 4 years, IQR 1.25–7.5], and in two [20%] patients the two conditions were diagnosed simultaneously. Among the four patients who had a CRC diagnosis after IBD diagnosis, only one patient was receiving immunomodulatory therapy [azathioprine, infliximab, and vedolizumab in chronological order] between the IBD diagnosis and the CRC diagnosis. Eight out of the 10 [80%] patients with CRC had Lynch syndrome [four with UC and four with CD] and two [20%] had FAP [both with CD].

Eighteen [69.2%] patients underwent colectomy or abdominal surgery: nine patients due to CRC diagnosis, five patients preventively due to the underlying HCCS, three patients preventively due to the underlying HCCS and concomitant active IBD disease [all with CD], and one patient because of active IBD disease [UC]. Among these 18 patients, seven [38.9%] underwent ileal pouch-anal anastomosis, six [33.3%] underwent ileostomy, three [16.7%] underwent ileorectal anastomosis, one patient had a sigmoid resection, and another patient had a left hemi-colectomy [Table 1]. One patient died due to CRC with metastasis, which was diagnosed simultaneously to IBD and HCCS.

4. Discussion

To date this multicentre case series, which describes the characteristics of patients with IBD and concomitant diagnosis of HCCS, is the largest to report on this rare association.

We described 26 cases of patients with IBD [10 with UC, 15 with CD and one with IBD-U] and HCCS diagnosed before [11/26], after [11/26], or concurrently [4/26] with IBD diagnosis. The majority of patients had a diagnosis of Lynch syndrome [16/26], and the most frequent genetic mutations were those of APC [7/26] and MLH1 [7/26]. Overall, 10 patients [38.5%] developed CRC and one died because of it. Approximately 70% of patients underwent colectomy or abdominal surgery; 65% [17/26] of patients were treated with immunomodulatory therapy, and among these three interrupted the drug because of side effects. Moreover, one patient treated with vedolizumab developed CRC after 4 years of treatment, despite yearly colonoscopy surveillance.

It is well recognised that IBD and HCCS are two important risk factors for the development of CRC.⁹ The majority of our patients [n = 16] had Lynch syndrome, and half of them [n = 8] developed CRC, mostly after IBD diagnosis [n = 4]. Lynch syndrome is associated with a 6–77% lifetime risk for CRC due to the particular mismatch repair protein gene mutation.¹⁷ McNamara et al. reported 12 confirmed cases of Lynch syndrome and concurrent IBD, and four [33%] of them developed CRC.¹⁶ These four IBD patients were receiving routine endoscopic surveillance at the time of CRC diagnosis; however, none of them had the diagnosis of Lynch syndrome until the development of CRC. In our cohort, among patients with Lynch syndrome who developed CRC [n = 8], four had the diagnosis of IBD before, three after, and one simultaneously with CRC diagnosis.

These considerations might suggest the importance of considering HCCS in patients with IBD who develop CRC, particularly if they are young at the time of CRC diagnosis.

Another study, comparing patients with Lynch syndrome with and without IBD, found that the rate of CRC development was not significantly different between the two groups. However, all CRC cases had UC, resulting in a higher cumulative CRC incidence for this subgroup of patients with IBD.¹⁸ Conversely, in our cohort, among the eight patients with Lynch syndrome who developed CRC, four patients had UC and the rest [n = 4] had CD [two with ileal and two with ileocolonic disease].

In the literature, few case reports on FAP in patients with IBD are reported, and all these cases had a diagnosis of CD. Gentile et al. and Fidalgo and colleagues reported two cases of patients with a history of FAP and pouchitis, who ultimately were found to have CD.^11,12 Fukushima et al. and reported a case of FAP initially intended to undergo total proctocolectomy and ileal pouch-anal anastomosis.¹³ However, CD was intraoperatively found and an ileostomy was constructed.¹³ In our case series, we reported seven cases of FAP and all had a diagnosis of CD. Among these seven cases, five patients had a diagnosis of CD after that of FAP, one before, and another concurrently. These findings suggest a potential association between FAP and CD.

There is no evidence in the medical literature regarding the use of immunomodulators in patients with HCCS and IBD. Sixteen of our patients received immunomodulatory therapy. Four of them developed drug-induced side effects, three of whom required drug interruption. Moreover, one patient treated with vedolizumab developed CRC after 4 years of treatment, despite yearly colonoscopy surveillance. Although it is difficult to speculate on this finding, given that vedolizumab blocks the traffic of lymphocytes in the digestive tract, this may, as previously suggested¹⁹ impair the immunosurveillance of digestive cancers in patients with HCCS and IBD. Long-term safety data on vedolizumab in patients with IBD do not suggest an increased risk for CRC among users,²⁰ but patients with HCCS are poorly represented in clinical trials. Therefore, more safety data from real-world cohorts of patients with genetic CRC predisposition are needed.

Our study has several limitations, as it was a retrospective case report data collection and it relied on voluntary submission of cases by physicians who responded to the ECCO calls and thus might be subjected to geographical and selection biases. Due to the relatively small sample size, definitive conclusions on association between IBD-related and HCCS-related factors are limited.

In conclusion, to date this is the largest case series of patients with IBD and HCCS. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome, whereas all patients with FAP had a concomitant diagnosis of CD. Finally, these data highlighted the high malignancy and surgical intervention rates in this IBD cohort. The optimal medical approach in these patients still needs to be addressed.

Funding

No specific funding has been received for this project.

Conflict of Interest

BB: has served as speaker for Alfasigma, Janssen, Procise, Sofar, Takeda; has served as consultant for Doxapharma. ES: has served as speaker for Abbvie, AGPharma, Alfasigma, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Unifarco; has served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & co, Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; received research support from Reckitt Benckiser, SILA, Sofar, Unifarco. BV: has received research support from Pfizer; has received speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion, and Viatris; has received consultancy fees from Alimentiv, Applied Strategic, Atheneum, Bristol Myers Squibb, Galapagos, Guidepont, Ipsos, Janssen, Progenity, Sandoz, Sosei Heptares, and Takeda. MF: has served as speaker for Abbvie, Ferring, Tillots, Takeda, Janssen, MSD, Celgene, Gilead, Fresenius, Amgen, Biogen, Mylan, Boehringer, CTMA, Pfizer, Galapagos, Celltrion. DP: has served as speaker for Janssen, Pfizer, Takeda; consultant for Galapagos, Janssen, and Pfizer. LB: has served as speaker for Pharmanutra and Janssen. AB: has served as speaker for Takeda, Janssen, Alfasigma, Sofar; has served as board member for Biogen. IG: has received research support from Pfizer, European Crohn’s and Colitis Organisation [ECCO], and the International Organization for the Study of Inflammatory Bowel Diseases [IOIBD]. AS: has served as speaker for Pfizer and Takeda. NT: reports personal fees from AbbVie, Falk Foundation, Janssen, and Takeda outside the submitted work. GD, IL, MT, PE: none.

Acknowledgements

ECCO CONFER projects are based on an initiative introduced by ECCO to support individual investigators in developing rare case series, by collecting enough similar cases among the IBD Community. This support includes the dissemination of a call for similar cases, as well as an assessment of the feasibility of the cases by the ECCO CONFER Steering Committee. It does not include any financial support nor any input into the scientific collection of the data or the analysis or the publication of the data collected. ECCO, and/or any of its staff members, may not be held liable for any information published in good faith in the ECCO CONFER articles.

Author Contributions

BB: principal investigator for the study, conceived the study idea and prepared the manuscript. BB, ES, BV, MF, DP, LB, AB, GD, IG, IL, AS, NT, MT, PE contributed to the cases and critically revised the manuscript. PE: case manager for the study, supervised the project, and critiqued the manuscript. All authors approved the final version.

Conference presentation: Seventeenth Congress of ECCO—Inflammatory Bowel Diseases 2022, e-poster presentation [P119].