Introduction

Clostrioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostrioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings.

Aims & Methods

Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed.

Results

When prediction performance of our model was evaluated, the area under the receiver operating characteristic curve was 0.952 (95% CI: 0.932-0.973) in internal validation and 0.972 (95% CI: 0.968-0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased.

Conclusion

Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications

Disclosure

Nothing to declare

Clinical Case Summary

A 72-year-old patient with a history of atrial fibrillation on treatment and cirrhosis, presented with subjective fevers and abdominal distention for 2 months. An initial laboratory work-up showed an inflammatory syndrome and a prothrombin level of 40 %. The rest of the work-up was unremarkable. A computed tomography (CT) scan of the abdomen showed dysmorphic liver with signs of portal hypertension and abundant ascites with micronodular infiltration of the greater omentum.
Paracentesis showed ascitic fluid (AF) with total nucleated cells 2400 with 5% neutrophils and 87% lymphocytes and protein levels at 40. Cytology was negative for malignancy.
Initially, the patient was considered for diagnostic laparoscopy to investigate the persistent abdominal symptoms. However, in light of the current epidemiological context, marked by a heightened incidence of tuberculosis in the region, a systematic workup for tuberculosis was prioritized. Direct examination and culture for acid-fast bacilli (AFB) were negative, however Xpert Mtb/Rif was positive. standard chest X-ray showed a normal parenchyma with a small right pleural effusions. Thoracentesis was done and pleural fluid AFB culture was negative.
He was started on isoniazid, rifampin, pyrazinamide and ethambutol and was discharged with a close follow up.

Clinical Case Summary

Introduction: Wilson’s disease is a rare inherited liver disorder caused by copper metabolism dysfunction,whereas Crohn’s disease is a chronic inflammatory bowel condition.The co-occurrence of both conditions in an adolescent is extremely rare and becomes particularly noteworthy when associated with severe complications.
Case presentation: We report a 17-year-old male with cirrhotic Wilson’s disease,stable on D-penicillamine, who developed severe anal pain and bloody diarrhea.On proctologic examination,he had hemorrhoids, a s crotal fissure,and a non-draining anal fistula.
Laboratory investigations revealed severe anemia (Hb 4.4 g/dL),leukopenia,and elevated C-reactive protein. Colonoscopy showed multiple ileocolic ulcers on edematous mucosa, suggestive of active Crohn’s disease, confirmed by histopathological examination of biopsies. Pelvic MRI identified a grade II active, intersphincteric, abscessed perianal fistula. Antibiotic therapy was initiated accordingly. The patient was treated with high-dose intravenous corticosteroids for three weeks, followed by oral tapering, leading to significant clinical and laboratory improvement. However, during hospitalization, he developed disseminated intravascular coagulation (DIC) with thrombotic microangiopathy, requiring transfusion of fresh frozen plasma.His condition improved favorably thereafter
Discussion: The coexistence of Wilson’s and Crohn’s diseases is extremely rare. This case stands out for the onset of severe Crohn’s in a patient with chronic liver disease, a complex perianal fistula needing multidisciplinary care,and DIC with thrombotic microangiopathy—likely from systemic inflammation. It highlights the diagnostic and therapeutic challenges in adolescents with multiple chronic illnesses

Conclusion: The association between Wilson’s disease and Crohn’s disease is exceedingly rare. This case emphasizes the need for a multidisciplinary approach in managing complex patients, particularly when faced with severe complications.

Clinical Case Summary

A 12-year-old girl, previously healthy, was admitted to pediatric ward with jaundice, itchy skin, and
general weakness for about 10 days. Physical examination revealed jaundice, discrete exophthalmos,
and tachycardia. Laboratory tests showed significantly elevated transaminases, total and conjugated
bilirubin and bile acids, with a mild increase in GTP. INR, ammonia and albumin levels remained within the range. In the first stage of diagnosis, infectious factors (primary and secondary hepatotropic viruses), Wilson's disease and alpha-1-antitrypsin deficiency were ruledout. Elevated ANA antibody levels and increased serum IgG titers have been found, but a liver panel was negative. Imaging studies (MRI) showed no changes in the liver and bile ducts. After consultation with the pediatric gastroenterologist thyroid function tests were performed which revealed: undetectable TSH, high fT4 and fT3. In the course of further diagnostics, positive titers of anti-Tg, anti-TSHr, and anti-TPO antibodies and enlarged thyroid in USG were obtained, which led to a diagnosis of Graves' disease. The treatment included methimazole and propranolol, which stabilized the patient's general condition and improved laboratory parameters within a few days. Currently, the patient is continuing methimazole therapy and remains euthyroid, with liver function tests completely normalized.
The clinical case illustrates the coexistence and mutual influence of liver and thyroid diseases. The patient was initially suspected of having AIH induced by autoimmune thyroid disease. The negative liver panel results could indicate a seronegative variant of AIH. The patient was scheduled for a liver biopsy to establish a definitive diagnosis, but the test was postponed due to a marked improvement in liver parameters as a result of the control of thyrotoxicosis. Complete clinical and laboratory improvement after treatment with thionamides, without the use of typical AIH therapy, argues against this diagnosis.

Disclosure

No conflict of Interest

Clinical Case Summary

There is no clear consensus on the treatment of autoimmune hepatitis (AIH) with insufficient response to standard immunosuppressive therapy. ERN RARE-LIVER suggests infliximab as a third-line therapy. We report on a 35-year-old man diagnosed with AIH type 1 and and ulcerative pancolitis (UC) in 2006. AIH exhibited inadequate response to steroids and another immunosuppressive drugs (azathioprine, mycophenolate mofetil, tacrolimus). A liver biopsy in 2013 revealed severe activity and fibrous septa. Despite mild UC, infliximab was introduced in 2014 at 5 mg/kg every 4 weeks (then every 8 weeks) in conjunction with steroids and azathioprine (AZA), resulting in clinical and biochemical response in both diseases. By 2020, sustained biochemical response was achieved with infliximab, prednisone and AZA without infectious side effects. A liver biopsy in March 2023 revealed chronic hepatitis with no inflammatory activity and rare fibrous septa (METAVIR scoring system: activity grade 0, staging grade 2). Considering long-term risks of triple immunosuppression and the persistent remission of AIH and RCU, infliximab was discontinued in June 2023. Blood tests in October 2023 indicated a resurgence of transaminases (ASTx12,6, ALTx19,7 ULN) and IgG (x2,1 ULN), rise in bilirubin (total/conjugated 2,83/1,40 mg/dl). Patient was hospitalized, intravenous methylprednisolone was administered with mild decrease in liver tests. Considering that AIH flare, infliximab was reintroduced in November 2023 together with prednisone and AZA. Blood tests after 2 weeks showed AST normalization, ALT x1,3 and IgG x1,2 ULN, bilirubin total/conjugated 1,89/0,36 mg/dl. No adverse events were experienced. Our case underscores that in rare instances, AIH may necessitate triple combination therapy to induce and maintain remission, including infliximab. Given the possible long-term risks of this level of immunosuppression, it is mandatory to carefully evaluate such patients in a case-by-case manner.

References

AW Lohse, M Sebode, MH Jørgensen et al. Second-line and third-line therapy for autoimmune hepatitis: A position statement from the European Reference Network on Hepatological Diseases and the International Autoimmune Hepatitis Group. Journal of Hepatology 2020 vol. 73, 1496-1506

Clinical Case Summary

A 77-year-old patient with diabetes insipidus underwent an abdominal computed tomography scan due to upper quadrant abdominal pain. The exam showed concentric thickening of the main and intrahepatic bile ducts. A subsequent magnetic resonance cholangiopancreatography, with diffuse thickening of the main and intrahepatic bile ducts, with diffusion restriction and reduced biliary duct caliber, without lithiasis. Due to the suspiecion of a malignant biliary stricture, the patient was proposed for endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy. The cholangiogram showed diffuse rarefaction of the intra and extrahepatic bile ducts, with focal dilatation of the intrahepatic bile ducts. After biliary sphincterotomy, cholangioscopy revealed a narrowed main bile duct extending to the hepatic hilum, with neovascularization, and papillary projections. Multiple biopsies were taken and a plastic stent was placed. Cholangioscopy-guided biopsy revealed granulation tissue and stroma with numerous histiocytes and eosinophils. Immunohistochemistry identified histocytes expressing CD68, S100, and CD1a, consistent with biliary involvement by Langerhans Cell Histiocytosis. The procedure was complicated by acute pancreatitis, requiring Intensive Care Unit admission. The patient’s hydroelectrolytic disorders were caused by pituitary involvement (lymphocytic hypophysitis associated with granulomatous disease). The patient started corticosteroid therapy with clinical and analytical improvement.
Langerhans Cell Histiocytosis is characterized by histiocytes proliferation, with progressive fibrosis due to tissue infiltration. In this case, diabetes insipidus was the first disease manifestation, due to lymphocytic hypophysitis. LCH is a rare cause of secondary sclerosing cholangitis, and early diagnosis through cholangioscopy was essential to initiate appropriate systemic therapy, preventing disease progression with multiorgan involvement.

Introduction

Eosinophilic esophagitis (EoE) is an inflammatory disease that is the leading cause of food impaction in children and young adults. EoE is thought to be a food antigen-driven allergic disease, best characterized by eosinophil-predominant inflammation, esophageal dysfunction, and expression of Th2 cytokines. Thymic stromal lymphopoietin (TSLP) is a cytokine primarily secreted by epithelial cells in barrier tissues in response to danger signals, infectious agents, Th2 cytokines and environmental antigens. TSLP is a master regulator of Th2 inflammation. Genetic studies have linked single nucleotide polymorphisms in TSLP to Th2 driven diseases, including eosinophilic esophagitis. Recent single-cell sequencing studies demonstrated memory CD4 T cells expressing TSLP receptor correlated with esophageal eosinophil counts. While some data suggest a key role of TSLP in the pathogenesis of EoE, its relative contribution has not been established in in vivo models.

Aims & Methods

Experimental EoE was induced in male wild type mice by an initial skin-sensitization using oxazolone (OXA, 17 days) followed by intraesophageal challenge with oxazolone or vehicle control (19 days, total duration 36 days). TSLP expression in the esophagus was measured during the sensitization and challenge periods. To determine the role of TSLP in EoE, treatment with a TSLP neutralizing antibody or isotype control began prior to esophageal challenge. Eosinophil counts, epithelial and lamina propria thickening, epithelial cell proliferation and esophageal vascularization were assessed in esophageal tissue on day 36.

Results

Intraesophageal challenge with OXA induced a transient upregulation of TSLP in the esophagus at day 29, with TSLP being expressed primarily in esophageal epithelial cells. Inhibition of TSLP activity with a blocking antibody in OXA sensitized mice resulted in 60% fewer eosinophils compared to isotype treated controls (p<0.001). Additionally, anti-TSLP treatment also induced statistically significant reductions in epithelial and lamina propria thickness and basal cell zone proliferation (Table 1). When assessed by region, TSLP neutralization statistically significantly reduced esophageal vascularization in regions with the highest degree of eosinophil infiltration.

Conclusion

This is the first time neutralization of TSLP in an experimental mouse model of EoE is reported, demonstrating a key role of TSLP in EoE disease pathogenesis. Inhibition of TSLP markedly decreased esophageal eosinophilia, a key diagnostic criterion for EoE. Other histologic features of EoE were also reduced upon TSLP neutralization. Together with genetic and mechanistic studies associating TSLP with EoE pathogenesis, this data suggests TSLP may serve as a treatment target for patients with EoE.

Disclosure

KK, LW, and HO are employees of Uniquity Bio