Introduction

Patients with immune mediated inflammatory diseases (IMIDs) on immunosuppressive therapies have attenuated vaccine responses (1-3) and are prone to severe infections. Knowledge of COVID-19 outcome following vaccine and hybrid immunity, and identification of protective anti-Spike antibody concentrations are important to further develop vaccine strategies in this vulnerable patient group.

Aims & Methods

In this prospective observational study, adult patients with IMID on immunosuppressive therapies were followed from February 15, 2021, to February 15, 2023. Throughout the study, patients and controls reported data regarding COVID-19, COVID-19 related hospital admissions were recorded from The Norwegian Patient Registry. Anti-Spike antibodies were assessed 2-4 weeks following vaccination and COVID-19. The objectives of this study were to investigate the outcomes of COVID-19 in a large cohort of IMID patients compared to healthy controls, and to identify any associations between anti-Spike antibody concentrations and disease course.

Results

Of 2250 IMID patients included in the study, a total of 1729 with a documented COVID-19 history were included in the present analyses (305 Crohn’s disease, 215 ulcerative colitis, 648 rheumatoid arthritis, 272 psoriatic arthritis, and 289 spondyloarthritis) (median age 54 years (IQR 42-64), 971 (56 %) females). Of the patients, 1080 of 1729 (62%) used anti-TNF treatment (65% monotherapy, 35% combination therapy).
1140 (66%) of patients and 236 of 350 (67%) healthy controls (HC) reported COVID-19, the majority (85%) within the Omicron era. COVID-19 reinfection was reported in in 141 (12%) patients and 32 (14%) HC (p=0.66). Compared to hybrid immunity (COVID-19 after three vaccine doses), the risk of COVID-19 was six times higher following vaccine series only (HR 5.9, (95% CI [4.45, 7.80]), p<0.001). Anti-Spike antibody concentrations <8000 BAU/ml were predictive of COVID-19 after three (HR 1.5 (95% CI [1.14, 1.90]), p=0.003) and four vaccine doses (HR 1.4 (95% CI [1.13, 1.83]), p=0.003), and in hybrid immunity (HR 2.6 (95% CI [1.32, 5.13]), p=0.006). In the entire cohort, the median anti-Spike antibody concentration after the 2^nd vaccine dose was 2823 BAU/ml (IQR 999-6199), after the 3^rd dose 6529 BAU/ml (IQR 2325-10140), after the 4^th dose 7624 BAU/ml (3809-12751) and following hybrid immunity 23506 BAU/ml (11423, 37007). Hospitalisation due to COVID-19 (severe disease) occurred in 22 (2%) patients, 9 (41%) before any vaccination, and none of HC. Four patients were admitted to intensive care. Prior to hospitalisation, the median anti-Spike antibody concentration was 444 BAU/ml (IQR 31-1634). Patients with severe disease were older than non-hospitalised (median age 61 years (IQR 48-74) vs. 54 (42-64), p=0.04) and had a higher frequency of comorbidities (19/22 (86%) vs. 474/1118 (42%), p=0.02). No COVID-19 related deaths occurred.
Prolonged COVID-19 (symptoms >14 days) were reported by 201 (18%) patients compared to 29 (12%) HC (p=0.09). The risk of prolonged disease was higher in the vaccine group compared to the hybrid group (HR 8.5 (95 % CI [3.84, 18.90]), p<0.001).

Conclusion

IMID patients and healthy controls had a comparable occurrence of COVID-19, prolonged disease and reinfection. However, severe disease developed only in the patient group. Hybrid immunity protects against COVID-19 and prolonged disease. A high anti-Spike antibody concentration protects against COVID-19, supporting the role of repeated vaccination in IMID patients on immune-suppressive therapy.

References

1. Jorgensen KK, Hoivik ML, Chopra A, Benth JS, Ricanek P, Moum PB, et al. Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scand J Gastroenterol. 2023:1-9.
2. Bjorlykke KH, Orbo HS, Tveter AT, Jyssum I, Sexton J, Tran TT, et al. Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. Lancet Rheumatol. 2023;5(1):e36-e46.
3. Syversen SW, Jyssum I, Tveter AT, Tran TT, Sexton J, Provan SA, et al. Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy. Arthritis Rheumatol. 2022;74(8):1321-32.

Disclosure

Have received speakers bureaus from Bristol-Myers Squibb and Roche

Clinical Case Summary

Whipple’s disease (WD), caused by Tropheryma whipplei, is a rare, multisystemic infection with a wide spectrum of clinical presentations. It may manifest acutely with nonspecific symptoms such as diarrhea, abdominal pain, fever, and fatigue, or present chronically. Diagnosis can be challenging due to its diverse manifestations, including cardiac, pulmonary, and neurological involvement. We describe a case of a 54-year-old male with a background of peroneal nerve dysfunction, admitted for progressive epigastric pain, nausea, vomiting, altered bowel habits, and recent mood changes. A comprehensive diagnostic evaluation was undertaken, including blood tests, abdominal ultrasound, computed tomography, and upper gastrointestinal endoscopy with biopsy. Diagnostic investigations revealed elevated cholestatic and pancreatic enzymes, raised CRP and ferritin levels, esophagitis, and distal duodenal swelling obstructing endoscope passage with inflammation around the ampulla of Vater. There were features of chronic pancreatitis with calcifications, pseudocysts (up to 27 mm), dilated Wirsung’s duct, and enlarged crescent lymph nodes. Histopathology showed extensive macrophage infiltration, and PAS staining was suggestive of T. whipplei infection. The patient was successfully treated with Ceftriaxone 2g orally daily for 30 days, followed by Trimethoprim/Sulfamethoxazole 960mg twice daily for one year. This case highlights an atypical presentation of WD, manifesting as upper gastrointestinal obstruction and recurrent acute pancreatitis, probably due to duodenal and ampullary inflammation impairing bile flow. It underscores the importance of considering WD in the differential diagnosis of complex and unexplained gastrointestinal symptoms. Presentations involving upper gastrointestinal obstruction and pancreatitis are rare. Early identification through intestinal biopsy and appropriate antimicrobial therapy is critical to avoid irreversible complications and improve outcomes.

References

Illustrative material:
1. Upper gastrointestinal endoscopy: view of the descending duodenum
2. Abdominal CT scan
3. Pathological findings: PAS staining

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) is an established endoscopic treatment for common bile duct stones and acute cholangitis. Due to its less invasiveness compared to surgery, it has been accepted as a first choice even for the elderly receiving anticoagulants. However, there is only a limited number of reports of the safety of EST after minimal cessation of anticoagulant based upon the Japan Gastroenterological Endoscopy Society (JGES)guideline.

Aims & Methods

To evaluate the safety, we aimed to clarify the bleeding risk in patients taking anticoagulants in our institute. Patients who underwent ERCP at double institutes from January 2018 to December 2021. Among them, we compared the rate of bleeding after EST and bleeding requiring blood transfusion in anticoagulant patients and non-administrators. Patients taking anticoagulants were allowed to discontinue the direct oral anticoagulant (DOAC) on the day before or the day of ERCP, and those who followed the JGES guideline for warfarin were included.

Results

ERCP was performed in 1616 patients and an analysis of a total of 882 patients of EST including 69 patients taking anticoagulants revealed that there were no significant differences in the bleeding rate although the blood transfusion rate was significantly higher in the DOAC group (2/52 3.9%) and antiplatelet drug combination cases (1/15 6.7%) compared to other cases (5/805 0.6%). Univariate and multivariate analyzes were performed according to background age, sex, hypertension, diabetes mellitus, heart disease, cerebrovascular disease, hemodialysis, platelet count decreased (less than 10x10⁴/μL), and urgency (within 24 hours after consultation). In the univariate analysis for EST bleeding, cerebrovascular disease, hemodialysis, and thrombocytopenia were significant risk factors(p<0.05). As a result of the multivariate analysis of these, only cerebrovascular disease was a significant risk factor (OR=2.11, 95%CI: 1.21-3.68, p=0.0086). In the univariate analysis for blood transfusion, DOAC users, cerebrovascular disease, and hemodialysis patients were significant risk factors(p<0.05). A multivariate analysis that added EST bleeding to these results also found significant risk factors for similar items. DOAC(OR=6.89, 95%CI: 1.06-44.65, p=0.043) and cerebrovascular disease(OR=18.85, 95%CI: 3.01-117.93, p=0.0017), hemodialysis(OR=55.68, 95%CI: 6.51-475.99, p=0.00024) were significant risk factors for severe bleeding requiring blood transfusion.

Conclusion

Although there were no significant differences between the bleeding rates of EST for those taking anticoagulants and those not taking anticoagulants, it was suggested that there is a possibility of serious bleeding requiring blood transfusion in patients receiving anticoagulants, especially DOAC.

Disclosure

none

Introduction

Non-invasive biomarkers are needed to improve the management of eosinophilic esophagitis (EoE). We investigated whether eosinophil and lymphocyte counts could be used to diagnose EoE among patients with dysphagia and assess histological, endoscopic, and clinical disease activity in patients with known EoE.

Aims & Methods

This was a prospective study conducted at four EoE referral centers (Pisa, Padova, Humanitas Research Hospital, Milano Policlinico San Donato). We enrolled consecutive patients undergoing esophagogastroduodenoscopy (EGD) for suspected or known EoE who had performed blood counts within one month before EGD. Histological remission and non-EoE-related dysphagia (NED) were defined according to current guidelines on EoE. Endoscopic characteristics were classified according to the EoE reference score (EREFS). Demographic, clinical and full blood count data were collected. After the EGD, all patients completed the Dysphagia Symptom Questionnaire over 14 days (DSQ). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to assess the diagnostic accuracy. Spearman’s test was used for correlations. Significance threshold was p<0.05.

Results

We included 210 consecutive patients. Of these, 123 had EoE (58.5% active; 41.5% in histological remission) while 87 had non-EoE dysphagia (NED). Characteristics in Table 1. Absolute eosinophil count (AEC) of active EoE was significantly higher than NED (335 vs 90/mm3; p<0.001), and so was eosinophil percentage (4.6% vs 1.1%; p<0.001), and median lymphocyte percentage (30 vs 27%; p<0.001). ROC curve analysis showed that a cut-off of 155 eosinophils/mm3 had an AUC of 0.85, with 71% specificity and 87% sensitivity for the identification of EoE among patients with dysphagia (Figure 1a). Other ROC analyses on the diagnosis of EoE reported in Table 2. With regards to disease monitoring, only eosinophil counts differed significantly between EoE and NED. Median AEC of active EoE was higher than EoE in remission (335 vs 200/mm3; p<0.01), and so was eosinophil percentage (4.6 vs 1.4%; p<0.001) (Table 3). Based on ROC analysis, a cut-off of 325 eosinophils/mm3 had and AUC of 0.70 for the identification of histological remission in EoE, with a specificity of 52.7%% and sensitivity of 82.3% (Figure 1b) (Table 3). There was modest positive correlation between AEC and the EREFS with Spearman’s Rho of 0.4 (p<0.0001), but there was no correlation between AEC and DSQ scores (Rho= -0.01; p=0.9).

Conclusion

Our results show that the AEC in peripheral blood has good accuracy for the diagnosis of EoE in patients with dysphagia and moderate accuracy for monitoring histological disease activity. In addition, AEC was modestly correlated with endoscopic disease activity (EREFS score) but not with symptoms.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

Inflammatory Bowel Diseases (IBD) patients are associated to a higher risk of developing colonic dysplasia and colorectal cancer due to long-standing colonic inflammation and immunosuppressant therapies. They seem to have also a higher risk of developing extra-intestinal malignancies, such as cholangiocarcinoma, skin cancer, and others. Different studies have been conducted to assess whether a correlation exists between IBD, medical treatments and cancers, but the results are controversial.

Aims & Methods

Our study aimed to evaluate the risk factors of malignancies in our IBD patients, particularly considering the medication history.
In this single-center retrospective study, IBD patients with a history of at least one malignancy post-IBD diagnosis followed at the Gastroenterology Unit of Azienda Ospedale Università Padova were enrolled (cases). Demographics and clinical data, including medication information, were collected before and at the time of malignancy diagnosis. A group of IBD patients, matched by sex and age, without a malignancy history were also included (controls), considering the medications taken before and at the time of the last visit for comparison.

Results

Among 2213 IBD patients followed at our center (1212 males, 1040 CD, and 1173 UC), 153 cases (80 UC and 73 CD, 46.4% males, mean age at diagnosis: 38.4±14.7) and 50 sex and matched controls were included (30 UC and 20 CD, 52% males, mean age at diagnosis: 38.9±0.8). Twelve patients had two malignancies, and 2 had three. For the scope of our study, we considered only the first tumor. Results are shown in the Table 1. The mean time from IBD diagnosis to the first tumor was 15 years (SD 10.5). Considering malignancies, the most frequent in our population were breast cancer (27/1001 females, 2.7%), colorectal cancer (23/2213, 1%), melanoma (24/2213, 1.1%), and non-melanoma skin cancer (15/2213, 0.7%). Patients with colon cancer were younger at the time of IBD diagnosis (31.0±15.8 vs. 38.9±0.8), while patients with prostate and urinary cancer (11/2213, 0.5%) were older compared to controls (49.6±13.7 vs. 38.9±0.8). A lower percentage of patients with colon (13%), breast (4%), and prostate cancers (9.1%) had taken biological therapy before cancer occurrence, as compared to controls (44%, p<0.01). Finally, we observed a significantly higher number of melanoma and breast cancer patients taking azathioprine (AZA) at the time of cancer diagnosis for more than 4 years. No difference in terms of duration of AZA and biological therapies before cancer diagnosis was observed.

Table 1: Type and frequency of Malignancies and characteristics of the patients

Conclusion

Our study found that biological therapy was not associated to malignancies, while azathioprine use was associated with breast and melanoma cancers. A younger age at diagnosis was associated with colon cancer, while an older age with prostate and urinary cancers.