Clinical Case Summary

Cronkhite-Canada syndrome (CCS) is a rare gastrointestinal disorder characterized by multiple polyps throughout the digestive tract, often accompanied by ectodermal changes such as onychodystrophy. Here, we present a case of CCS in a 65-year-old female with an unremarkable medical history presented with chronic abdominal pain and diarrhea containing mucus and blood, occurring 3 to 4 times per day. Clinical examination revealed signs consistent with malnutrition. Angular deformities, suggestive of onychodystrophy, were noted, while no other significant gastrointestinal abnormalities were observed.
During physical examination, the patient displayed signs of malnutrition. Abdominal palpation revealed tenderness, particularly in the lower quadrants, without palpable masses or organomegaly. Bowel sounds were present and within normal limits.
Laboratory investigations revealed elevated levels of ferritinemia. Computed tomography revealed three suspicious thickened segments within the digestive tract: one located in the antral region, the second in the cecal region, and the third in the sigmoid region. Colonoscopy demonstrated an erythematous colonic mucosa with polypoid lesions. Pathological examination revealed an illdefined colonic polyp characterized by multiple cystically dilated glands within an edematous lamina propria, accompanied by lymphocytes, plasma cells, and numerous eosinophils, favoring the diagnosis of Cronkhite-Canada syndrome.
This case highlights the importance of considering Cronkhite-Canada syndrome in the differential diagnosis of patients presenting with chronic gastrointestinal symptoms, malnutrition, and onychodystrophy. Early recognition and appropriate management, including nutritional support and surveillance for complications, are crucial in improving outcomes for patients with this rare and challenging syndrome. Further research is needed to better understand the pathogenesis and optimal treatment strategies for Cronkhite-Canada syndrome.

Introduction

This study assessed typical symptoms (abdominal pain, bloating, diarrhoea, nausea, tiredness) in patients with celiac disease (CeD) following a gluten-free diet (GFD) and evaluated the association between symptom severity and quality of life (QoL) to address limited data in this area.

Aims & Methods

In the Virtual Celiac Symptoms Study (NCT05309330), patients reported daily symptoms using the Celiac Disease Symptom Diary 2.1^© (CDSD 2.1^©) over 12 weeks and completed patient-reported outcome measures (PROMs), with 7-day look-back, at specified timepoints, including the Impact of Celiac Disease Symptoms Questionnaire (ICDSQ) and the Patient Global Impression of Severity (PGI-S) measure. Spearman’s correlation coefficient (SCC) and generalized linear regression evaluated associations between symptom severity and QoL PROM scores and mean differences were adjusted for key demographics.

Results

In total, 480 participants completed the study (mean [standard deviation] age: 31 [15] years, 81.7% female, 93.8% White). For all CeD symptoms measured, there was a positive linear association between CDSD 2.1^© symptom severity and PROM scores (p <0.001). The SCC between symptom severity and PROMs was 0.45–0.62 (PGI-S) and 0.33–0.56 (ICDSQ). The strongest correlations between gastrointestinal symptom severity (abdominal pain, bloating, diarrhoea, and nausea) and PROMs were between PGI-S score and abdominal pain (SCC: 0.62) and bloating (SCC: 0.59). Patients with severe/very severe abdominal pain versus none had mean (95% confidence interval [CI]) 63.1% (53.2–73.6) and 217.5% (165.1–280.2) greater PGI-S and ICDSQ scores, respectively.

Conclusion

The results indicate that higher symptom severity is strongly associated with worse QoL in patients with CeD following a GFD and that CDSD 2.1^© assesses patient-relevant symptom severity in CeD.

Disclosure

MA, NC, DAL, SG and RS are employees and shareholders of Takeda. LMM was an employee of Takeda at the time of the study. JRM and SS are employees of Analysis Group, Inc., which received research support from Takeda Development Center Americas, Inc. DA has served as a consultant for Takeda Pharmaceuticals and Ironwood Pharmaceuticals. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda Development Center Americas, Inc. EL serves as a consultant for Takeda Pharmaceuticals and is an author for UpToDate (celiac section) for which he receives royalties.

Introduction

With a growing interest in sex-specific differences in bowel preparation outcomes, current literature shows inconsistent results. Females have been associated with poor bowel preparation [1], while males may have inadequate bowel preparation due to poor compliance with instructions [2]. Analyses of randomized clinical trials of 1L polyethylene glycol (PEG) plus ascorbic acid (ASC) indicated greater high-quality (HQ) cleansing success in females than in males despite greater adenoma detection in males [3].

Aims & Methods

The effectiveness and tolerability of 1L PEG+ASC was compared in males versus females in a large real-world population. This post-hoc analysis of an observational, multi-centre, retrospective study in Spain and Portugal included patients who received 1L PEG+ASC before undergoing a colonoscopy [4]. Cleansing quality was assessed using the Boston Bowel Preparation Scale (BBPS). Adequate success was BBPS ≥6 with all segmental scores ≥2 and HQ success was BBPS ≥8 with BBPS 3 in the right colon. Polyp detection rate (PDR), adenoma detection rate (ADR) and adverse events (AEs) were also assessed. Results are reported either as mean ± SD. Chic-square test was used to compare outcomes.

Results

A total of 13,169 patients, (M/F: 6,406/6,763 aged 57.6 ± 12.7 / 56.4 ± 13.4 years) were included. The main indication for colonoscopy was (in males vs females) colorectal cancer screening: 42.5% vs 41.2%; diagnostic: 25.9% vs 32.7%; follow up: 28.6% vs 23.9%; or other: 2.9% vs 2.2%. Bowel preparations were taken either as an overnight split dose (males vs females: 32.3% vs 33.2%) or a same-day split dose (67.7% vs 66.8%). Males and females had similar (97.5% vs 97.1%) colonoscopy completion rates. Incomplete colonoscopies due to poor bowel preparation quality were rare and occurred at similar rates in males vs females (0.7% vs 0.9%).
In the overall colon, adequate success was similar in males vs females (89.5% vs 89.1%) (p = 0.40) while HQ success was more frequent in females vs males (54.1% vs 51.8%; p = 0.007). In the right colon segment, adequate success was similar in males vs females (91.4% vs 91.6%; p = 0.61), while HQ success was more frequent in females vs males (50.7% vs 47.8%; p < 0.001). The mean BBPS was similar overall and by segment (Table). As expected from the literature, the PDR and ADR were greater in males vs females in the overall colon and in the right colon (Table).

Table. Sex differences in bowel preparation parameters with 1L PEG + ASC

Variable	Males (n=6,406)	Females (n = 6,763)	P-value
Overall colon adequate success, n (%)	5,734 (89.5)	6,023 (89.1)	ns
Overall colon high-quality success, n (%)	3,317 (51.8)	3,660 (54.1)	0.007
Right colon adequate success, n (%)	5,853 (91.4)	6,196 (91.6)	ns
Right colon high-quality success, n (%)	3,063 (47.8)	3,429 (50.7)	0.0009
Overall colon total BBPS, mean ± SD Right colon BBPS, mean ± SD Transverse colon BBPS, mean ± SD Left colon BBPS, mean ± SD	7.3 ± 1.8 2.4 ± 0.7 2.5 ± 0.7 2.5 ± 0.7	7.3 ± 1.9 2.4 ± 0.7 2.5 ± 0.7 2.4 ± 0.7	ns
PDR overall colon, n (%)	3,552 (55.5)	2,926 (43.3)	<.0001
PDR right colon, n (%)	1,643 (25.7)	1,381 (20.4)	<.0001
ADR overall colon, n (%) na	2,200 (47.3) 4,654	1,753 (37.7) 4,656	<.0001
ADR right colon, n (%) na	1,139 (27.2) 4,193	915 (21.5) 4,264	<.0001

^aNumber of patients for whom histological information was available.

Males had fewer adverse events than females (1.8% vs 2.7%; p = 0.0008). While 98.2% males did not report any adverse events, those who did reported nausea (0.9%) or vomiting (0.6%). Similarly, 97.3% females did not report any adverse events, but those who did reported nausea (1.5%) or vomiting (1.0%).

Conclusion

In real-world clinical practice, 1L PEG + ASC was effective and well tolerated in both males and females. Females attained greater HQ cleansing success both overall and in the right colon.

References

References:

1. Cirocco WC et al. Dis Colon Rectum 1995; 38:964–968
2. Ness RM, et al. Am J Gastroenterol 2001; 96:1797–1802
3. Epstein M et al. Endosc Int Open 2021; 09: E1324–E1334
4. Esteban López-Jamar JM et al. UEG Journal 2022, Vol 10 (S8); OP022

Disclosure

Fatma Akriche and Carmen Turbi Disla are employees of Norgine Ltd