"Per ELISA": Time to adopt anti-transglutaminase/deamidated gliadin peptide diagnostic combination in coeliac disease of adults?

BACKGROUND: Anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTg) play a pivotal role in coeliac disease (CD) diagnosis. Deamidated anti-gliadin peptides (DGP) were added to the CD diagnostic workup. AIMS: We aimed to compare the diagnostic accuracies of ELISA-based (a-tTg/DGP) and immunofluorescence-ELISA-based strategies (EMA/a-tTg) for CD diagnosis. METHODS: From November 2020 to November 2022, we undertook an observational prospective study including consecutive adult patients with suspected CD. All subjects were tested for EMA, a-tTg and DGP IgA. An ROC curve was plotted to establish the best specificity cut-off of a-tTg and DGP levels, which would predict the presence of Marsh≥2 and Marsh=3. The diagnostic accuracies of a-tTg/DG and EMA/a-tTg were compared. RESULTS: The study included 275 CD patients. Histology showed Marsh=1 in 9.9%, Marsh=2 in 4.5%, and Marsh=3 in 85.6.%. The best cut-off value of a-tTg for predicting Marsh≥2 was 42 U/mL, while the best cut-off for predicting atrophy was 68.4 U/mL. The best cut-off value of DGP for predicting Marsh≥2 was 56 U/mL, while the best cut-off for predicting atrophy was 78 U/mL. A-tTg/EMA showed 97% sensitivity and 100% specificity, whereas a-tTg/DGP showed 94% sensitivity and 100% specificity. CONCLUSION: A-tTg/DGP is accurate for CD diagnosis and could reduce costs and operator-dependency of EMA. DGP, together with a-tTg, could replace EMA in CD diagnosis.

Cyclic Neutropenia Mimicking Crohn's Disease: Two Case Reports and a Narrative Review.

Cyclic neutropenia is a rare hematological condition characterized by periodic fluctuations in neutrophil counts, with a 21-day periodicity. Clinical presentation varies from mild to severe forms of the disease, with the onset of recurrent fever, painful oral ulcers, recurrent bacterial infections, peritonitis, and septic shock. The availability of granulocyte colony-stimulating factor (G-CSF) has revolutionized the management and natural history of this disease, regulating the proliferation, differentiation, and maturation of the progenitor cells, and reducing the duration of neutropenia. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic pathologies that affect the gastrointestinal tract. The onset of both diseases may be at a young age (even during childhood or adolescence), and clinical manifestations may lead to misdiagnosis, due to similar characteristics such as recurrent infections, oral ulcers, perianal abscesses, and infertility. Moreover, the two pathologies are rarely associated, with different management and therapeutic options. Here, we describe two case reports of patients who underwent surgery because of diagnosis of complicated CD. After surgery, due to persistent neutropenia, the hematologist consultant confirmed suspicions of cyclic neutropenia, and G-CSF therapy was started with benefits, underlining the crucial importance of proper differential diagnosis.

David Against Goliath: Direct Comparison of Handheld Bowel Sonography and Magnetic Resonance Enterography for Diagnosis of Crohn's Disease.

BACKGROUND: Diagnosis of Crohn's disease (CD) requires ileo-colonoscopy (IC) and cross-sectional evaluation. Recently, "echoscopy" has been used effectively in several settings, although data about its use for CD diagnosis are still limited. Our aim was to evaluate the diagnostic accuracy of handheld bowel sonography (HHBS) in comparison with magnetic resonance enterography (MRE) for CD diagnosis. METHODS: From September 2019 to June 2021, we prospectively recruited consecutive subjects attending our third level IBD Unit for suspected CD. Patients underwent IC, HHBS, and MRE in random order with operators blinded about the result of the other procedures. Bivariate correlation between MRE and HHBS was calculated by Spearman coefficient (r). To test the consistency between MRE and HHBS for CD location and complications, the Cohen's k measure was applied. RESULTS: Crohn's disease diagnosis was made in 48 out of 85 subjects (56%). Sensitivity, specificity, positive predictive values, and negative predictive values for CD diagnosis were 87.50%, 91.89%, 93.33%, and 85% for HHBS; and 91.67%, 94.59%, 95.65%, and 89.74% for MRE, without significant differences in terms of diagnostic accuracy (89.41% for HHBS vs 92.94% for MRE, P = NS). Magnetic resonance enterography was superior to HHBS in defining CD extension (r = 0.67; P < .01) with a better diagnostic performance than HHBS for detecting location (k = 0.81; P < .01), strictures (k = 0.75; P < .01), abscesses (k = 0.68; P < .01), and fistulas (k = 0.65; P < .01). CONCLUSION: Handheld bowel sonography and MRE are 2 accurate and noninvasive procedures for diagnosis of CD, although MRE is more sensitive in defining extension, location, and complications. Handheld bowel sonography could be used as effective ambulatory (or out-of-office) screening tool for identifying patients to refer for MRE examination due to high probability of CD diagnosis.

Impact of Sarcopenia on Clinical Outcomes in a Cohort of Caucasian Active Crohn's Disease Patients Undergoing Multidetector CT-Enterography.

(1) Background: Sarcopenia has a high incidence in Crohn's disease (CD) with considerable heterogeneity among ethnicities and variable impact on clinical outcomes. Aim: to assess the impact of sarcopenia on clinical outcomes in a cohort of Caucasian patients with active CD undergoing CT-enterography (CTE) for clinical assessment. We further investigated the prevalence of sarcopenia and its predictors. (2) Methods: Caucasian CD patients with moderate−severe clinical activity, who underwent CTE in an emergency setting, were retrospectively recruited. The skeletal muscle index (SMI) at the third lumbar vertebra was used to detect sarcopenia in the early stages. Clinical malnutrition was defined according to global clinical nutrition criteria. Clinical outcomes included the rate of surgery and infections within one year. (3) Results: A total of 63 CD patients (34 M; aged 44 ± 17 years) were recruited, and 48 patients (68.3%) were sarcopenic. Malnutrition occurred in 28 patients (44.4%) with a significant correlation between body mass index (BMI) and sarcopenia (r = 0.5, p < 0.001). The overall rate of surgery was 33%, without a significant difference between sarcopenic and non-sarcopenic (p = 0.41). The rate of infection in patients with sarcopenia was significantly higher than in non-sarcopenic (42%vs15%, p = 0.03). BMI (OR 0.73,95%, CI 0.57−0.93) and extraintestinal manifestations (EIM) (OR 19.2 95%, CI 1.05−349.1) were predictive of sarcopenia (p < 0.05). (4) Conclusions: Sarcopenia was associated with an increased rate of infections, and it was observed in 68.3% of the Caucasian cohort with active CD.

Exploring the concept of deep remission in Crohn's disease: correlation between transmural healing and biomarkers.

Background: While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn's disease (CD), little is known about the real significance and clinical impact of deep remission (DR). Objectives: To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. Design: Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. Methods: A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. Results: Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 µg/g to 260 ± 354.9 µg/g (p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 µg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 µg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). Conclusion: An FC < 94 µg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics.