Eosinophilic gastrointestinal disorders, including eosinophilic esophagitis, gastroenteritis, and colitis, refer to a spectrum of clinical diseases that present with variable degrees of infiltration of the gastrointestinal tract by eosinophils in the absence of other known causes of tissue eosinophilia. Clinical symptoms and laboratory findings are usually non-specific and may or may not be accompanied by peripheral blood eosinophilia. The extent of eosinophilic infiltration of the gastrointestinal wall varies from mucosal to transmural and serosal involvement. Diagnosis requires presence of gastrointestinal symptoms, demonstration of gastrointestinal eosinophilia by biopsy, and exclusion of other known causes of tissue eosinophilia. Many studies have pointed toward the eosinophil as the major offender; however, the exact functional role of the eosinophil in the pathogenesis of eosinophilic gastrointestinal disorders remains unclear. The roles of T-helper-2 cytokines and other mediators, such as eotaxin-1 and interleukin-5, have gained significant importance in the pathobiology of eosinophilic gastrointestinal disorders. Current understanding of treatment is based on case reports and a few case series, as there is a lack of large prospective studies. Steroids are currently the mainstay of therapy, but the roles of other drugs such as leukotriene inhibitors, mast cell stabilizers, interleukin-5 inhibitors, and anti-immunoglobulin E, along with other targets in the immune pathway, are currently being explored.
Background and Aims
Liver disease in Alagille syndrome is highly variable. Many of these patients presenting with severe cholestasis early in life improve spontaneously; 10–20% however, have progressive disease. It is currently not possible to predict long-term hepatic outcomes in Alagille syndrome. This international, multicenter study was aimed at identifying early life predictors of liver disease outcome.
Methods
Retrospective clinical, laboratory and radiographic data from a cohort of 144 Alagille syndrome patients, whose long-term hepatic outcomes had been determined a priori based on previously published criteria, were collected.
Results
Sixty-seven had mild and 77 severe hepatic outcome. Univariate analysis demonstrated that cholestasis and fibrosis on biopsy, as well as the presence of xanthomata were significantly different between the groups (p<0.05 for all). Mixed model analysis revealed that total serum bilirubin and serum cholesterol were also associated with outcome (p=0.001 and p=0.002, respectively). Graphical representation of the data revealed a change in total bilirubin levels between 12 and 24 months of age in the mild group. Recursive partitioning identified a threshold for total bilirubin of 3.8 mg/dL (65mmol/L) in that age-frame that differentiated between outcomes. A multivariable logistic regression model was developed using fibrosis, xanthomata and the total bilirubin cutoff of 3.8 mg/dL (65mmol/L), which generated an area under the ROC of 0.792.
Conclusions
The long-term hepatic outcomes of patients with Alagille syndrome can be predicted based on serum total bilirubin between the ages of 12–24 months combined with fibrosis on liver biopsy and presence of xanthomata on physical examination.
A 3-year-old girl presented with hematochezia. Her medical history included heart transplantation for hypoplastic left heart syndrome. Investigations demonstrated an Epstein-Barr virus polymerase chain reaction of 2307 genomes. Magnetic resonance enterography of the abdomen showed changes consistent with posttransplant lymphoproliferative disorder (PTLD) (Fig. 1). Her tacrolimus target trough was decreased to 4 to 7 ng/mL. Her initial colonoscopy showed ulcerations in the sigmoid colon and biopsies confirmed polymorphic PTLD (Fig. 2). She was treated with 4 weekly doses of rituximab and she remained clinically stable. Repeat colonoscopy to assess resolution of PTLD revealed a large perforation of the sigmoid colon; the patient subsequently underwent immediate bowel resection (Fig. 3). The gross specimen (Fig. 4) revealed granulation tissue, suggesting the perforation occurred before the colonoscopy. The pathology demonstrated persistent PTLD.PTLD is a rare but potentially fatal complication of solid organ transplantation. Extranodal involvement is highest within the gastrointestinal (GI) tract (1). In our case, rituximab, an anti-CD20 monoclonal antibody, was used to treat PTLD; however, its use has been associated with spontaneous GI perforation from rapid chemotherapeutic lysis of the tumor (2). Rituximab should be used cautiously in GI presentations of PTLD, especially in advanced disease and patients with multiple sites of involvement (3).
range, 1-201 months) after ileostomy closure. CD was diagnosed by afferent limb inflammation (n ¼ 20; 61%), development of perianal disease (n ¼ 6; 18%), small bowel ulceration on subsequent small bowel evaluation (n ¼ 3; 9%) or the presence of 2 or more of the above findings (n ¼ 4; 12%). The sole clinical predictor for the development of CD after IPAA was younger age at disease onset. The odds of developing CD increased by 4% for each year that IBDU was diagnosed at a younger age (Figure). Upon stratifying the patients to those # 20 years of age (n ¼ 54; 36%) and those 21 years of age and above, the odds ratio (OR) of developing CD in the older age group was 3.1 (P ¼ 0.005). CONCLUSIONS: Younger age at disease onset is the only clinical factor associated with the development of CD after IPAA for IBDU. Patients with IBDU undergoing IPAA with young age at disease onset should be counseled about a potentially higher risk of developing CD.
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