Clinical Case Summary

Case report: A 47-year-old woman presented with persistent abdominal bloating, cytolysis and hyperalkaline phosphatase. The patient was underweight. Over 10 years, pancreatic hyperamylasemia (>900 U/l), thrombocytopenia and anemia with low iron and folate levels are observed. Medical history - one spontaneous abortion, 2 children conceived by in vitro fertilization. Viral, autoimmune and genetic liver diseases, autoimmune thrombocytopenia, macroamylasemia, Helicobacter pylori and Giardia lamblia infection were excluded. Immunoglobulins and calprotectin were normal. Serological tests for Celiac disease (CD) detected a positive result only for antigliadin Ig G. Abdominal tomography scan did not detect pathological changes. Duodenoscopy revealed flattening of the intestinal villi suggestive of CD. Duodenal biopsy determined a morphological picture characteristic of CD: type 3c/B2 according to the Marsh-Oberhuber criteria. It was recommended a gluten-free diet, iron and folate therapy. At repeated check-up after 3 months, the patient's condition showed significant improvement, and no changes were detected in the laboratory tests.
Discussion: CD can be diagnosed at any age and can present with a wide range of associated or isolated clinical manifestations. Evaluation of the causes of various biological abnormalities may lead to the diagnosis of CD. The presented case highlights atypical clinical presentations that can be associated with CD. Despite the evolution of serological test performances, there are significant problems regarding the diagnosis in atypical conditions, especially in the patient with intestinal atrophy. In such situations, the intestinal biopsy remains the gold standard diagnosis for CD.
Conclusion: The non-classical clinical presentation of CD is becoming increasingly common in the daily practice of the physician, which requires an awareness of its many clinical faces with atypical forms.

References

- 2 illustrative materials with fragments of biopsy from duodenal mucosa (A - complete villous atrophy, stage 3c according to Marsh-Oberhuber, cryptic hyperplasia by numeral growth and depth of the glandular layer. B - m​arked lymphocytic infiltrate within the lamina propria, minor eosinophilia, hyperplastic crypts, slightly distorted architecture, complete villous atrophy).
- 4 illustrative materials from duodenoscopy

Disclosure

None to declare.

Introduction

Crohn's disease (CD) is a heterogeneous condition with potentially complicated course. We aimed to evaluate the rates and risk factors for complicated disease course within a real-world, prospective inception cohort of patients with newly diagnosed CD (ndCD).

Aims & Methods

This prospective, longitudinal cohort study included adults with ndCD managed at a tertiary referral center. Treatment decisions were made at the discretion of the treating physician. The key outcomes were: (1) complicated-disease course - defined as CD-related hospitalization, surgery, steroid dependency, or the use of ≥2 biologics; (2) extra-complicated disease course - defined as recurrent or prolonged hospitalization (>5 days), multiple perianal procedures, intestinal resection, steroid dependency, or the use of ≥3 biologics; and (3) phenotype progression. Kaplan-Meier survival analysis was used to assess rates of complicated course over 5 years, and multivariable Cox regression models were applied to identify baseline risk factors.

Results

A total of 192 patients with ndCD were enrolled; 70% presented with an inflammatory phenotype (B1) (see Table 1). Overall, 150 patients (78.1%) were recommended to start biologic therapy, with half receiving this recommendation within 4.1 months (95% CI: 2.1-6.3) from diagnosis. Of these, 134 patients (89.3%) initiated treatment - 50% within 6 months and 63.6% within 12 months. Cumulative outcome rates at 1, 3, and 5 years post-diagnosis were: complicated course - 24.2%, 35.9%, and 51.3%, respectively; extra-complicated course - 15.6%, 20.5%, and 29.0%, respectively; phenotype progression - 1.6%, 5.5%, and 10.6%, respectively. In a multivariable analysis, patients with a progressive phenotype (B2/B3) at diagnosis had significantly increased risk for complicated (HR 3.3, 95% CI:2.0-5.7) and extra-complicated (HR 6.7, 95% CI:3.1-14.4) disease course. Additional risk factors included elevated inflammatory markers and disease extent at diagnosis. We further analysed the subgroup of 33 patients with a B1 phenotype (~25% of those with a B1 phenotype) who were not recommended biologic therapy by their treating physician. In this subgroup, the complicated course was markedly low, 3.0%, 6.3%, and 11.5% at 1, 3, and 5 years, respectively, and none developed an extra-complicated course. Notably, this subgroup exhibited significantly lower inflammatory indices (CDAI, HBI, CRP, and fecal calprotectin) at diagnosis compared to patients for whom biologics were recommended (all p<0.001).

Table 1:

Sex, Female, n (%)	88 (45.8)
Age, median (IQR)	26 (21-36)
BMI (kg/m2), median (IQR)	21.7 (19.9-25.2)
Never smokers, n (%)	139 (72.4)
Family history of IBD, n (%)	58 (30.2)
Extraintestinal manifestations, n (%)	57 (29.7)
Ileal (L1), n (%) Colonic (L2), n (%) Ileocolonic (L3), n (%)	124 (64.6) 19 (9.9) 49 (25.5)
Perianal (P), n (%)	37 (19.3)
Inflammatory phenotype (B1), n (%) Stricturing phenotype (B2), n (%) Penetrating phenotype (B3), n (%)	137 (71.4) 36 (18.8) 19 (9.9)

Conclusion

In this real-world cohort, applying a best-practice treatment approach, over half of patients with ndCD experienced a complicated course within five years, primarily those with a progressive phenotype at diagnosis. Notably, a subset of patients with an inflammatory phenotype and low inflammatory burden had favorable long-term outcomes without biologics, underscoring the importance of early risk stratification to guide individualized treatment strategies.

Introduction

The definition of actionable GERD according to the Lyon v2.0 Consensus in patients with inconclusive diagnosis of GERD (acide exposure time [AET] that ranges among 4 and 6%) requires adjunctive metrics such as mean nocturnal baseline impedance (MNBI), total number of reflux events and reflux/symptom association (RSA) indices.

Aims & Methods

The aim of this study was to identify patients most likely to have a positive metrics on prolonged 96 hours wireless pH monitoring (PWPM) among patients with inconclusive AET values on 24 hours pH-impedance monitoring (MII-pH) off PPI. Secondary aim was to identify other MII-pH parameters predictive of GERD diagnosis.
This was a retrospective study that collected a series of patients with typical GERD presentation. All patients underwent:

• Endoscopy, to exclude the presence of erosive esophagitis (grade B or higher according to Los Angeles classification);
• Esophageal HRM to rule out motility disorders and calculate: esophago-gastric junction contractile integral (EGJ-CI), esophagogastric junction (EGJ) morphology, and Milan Score.
• MII-pH monitoring to assess AET values, total reflux events, MNBI, RSA and Lyon Score.
• PWPM performed for 96 hours within 1 month after MII-pH.
• Treatment (PPI) response was evaluated with VAS scale during follow-up.

Patients were categorized into 2 different groups: those with vs. without conclusive GERD on PWPM. MII-pH and HRM parameters were compared between the two groups.

Results

51 consecutive patients (24 female; median age 51yrs) were included: 15 patients (8 female, 49yrs, BMI 22.8) had non-conclusive PWPM for GERD (negative), while GERD was confirmed (positive) in 36 patients (16 female, 53yrs, BMI 26.8). There were no significant demographic differences. Prevalence of heartburn and regurgitation were comparable in both groups. Patients with confirmed GERD were more likely to respond to PPI treatment (positive 69% vs negative 59%, p=0.014).
Patients with confirmed GERD on PWPM had a higher AET (p<0.001), total reflux events (p < 0.001), and lower MNBI (p < 0.001) on MII-pH; lower EGJCI, and higher prevalence of hiatal hernia (p<0.001) on HRM; higher Milan SCORE (p < 0.001), and higher Lyon Score (p<0.01) compared to negative PWPM. See Table 1.

	Negative PWPM 96h (15)	Positive PWPM 96h (36)	P
PPI response (VAS)	59 (39, 69)	59 (39, 69)	0.014
Hiatal Hernia	0 (0%)	18 (50%)	<0.001
EGJ-CI	63 (46, 87)	20 (11, 30)	<0.001
MILAN SCORE	48 (42, 53)	196 (173, 234)	<0.001
AET (MIIpH)	1.60 (1.10, 2.90)	5.20 (3.75, 5.85)	<0.001
N REFLUX	25 (19, 29)	44 (36, 54)	<0.001
Symptom Index (+)	0 (0%)	10 (28%)	0.024
MNBI	2871 (2269, 3165)	1055 (910, 1247)	<0.001
LYON SCORE	1.00 (0.00, 2.00)	5.00 (3.00, 6.00)	<0.001

ROC analysis showed that MNBI is the strongest predictor of GERD (AUC 1.0), followed by the Milan (AUC 0.99, Sens 100%, Spec 93%) and Lyon Scores (AUC 0.97, Sens 80%, Spec 100%), total number of reflux events (AUC 0.9, Sens 86%, Spec 93%)
A subgroup of 13 patients (7 female) with an AET<4% but MNBI values <1500 Ohms on MII-pH, all (100%) were confirmed as having GERD on 96h PWPM.

Conclusion

We demonstrate that a low MNBI value on MII-pH is the strongest predicting factor of conclusive GERD diagnosis in patients with borderline or normal AET values. A sub-group of patients with AET <4% but very low MNBI (<1500 Ohms) on MII-pH showed conclusive GERD during subsequent 96 hour PWPM, establishing its longitudinal role in confirming reflux disease.

Disclosure

Conference Speech: Reckitt Benckiser; Malesci; Dr Falk, PharmaLine, AlfaSigma, Sanofi-Genzyme.
Advisory Board: Dr Falk; Astra Zeneca; Sanofi Genzyme, AlfaSigma
Research grant: Dr Falk; Sanofi Genzyme