Simone Ignatova

Adalimumab in budesonide and methotrexate refractory collagenous colitis

Abstract Background. We described three patients with collagenous colitis (CC) who developed side effects or were refractory to both budesonide and methotrexate and were given adalimumab (ADA) as a third-line treatment. Method/Patients. Three patients (two women, mean age 45 years and one man, 74 years old) were included. Mean bowel movements per day per week were calculated and stool weight/24 h registered prior to and following ADA treatment. ADA was given in doses 160 mg s.c. (baseline), 80 mg (week 2) and 40 mg (week 4). Sigmoidoscopies with biopsies were performed at baseline and after 6 weeks to examine changes in histology. The Psychological General Well-Being Index (PGWBI) and Short Health Scale (SHS) were used at baseline and after 6 weeks. Results. The two female patients tolerated the treatment well. The male patient developed, despite clinical response, side effects (vomiting, abdominal pain) after 80 mg of ADA and the treatment was stopped as side effects reoccurred after rechallenge. The two women were in clinical remission at week 6 and the mean stool frequency per day decreased from mean 11 to 2. Mean stool weight/24 h changed from 600 to 185 g. The quality of life improved drastically in all patients. There were no consistent changes in histology. Conclusion. ADA seems effective in budesonide and methotrexate refractory CC and can be administrated to selected patients to achieve clinical remission, improve quality of life and possibly avoid colectomy. Further studies for induction and maintenance treatment should be conducted to confirm efficacy and examine safety issues, even in long term.

Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase

Aliment Pharmacol Ther 2010; 32: 254–260

Intraepithelial lymphocyte distribution differs between the bulb and the second part of duodenum

BackgroundEvaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb.We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.MethodsThe number of CD3+ IELs was determined in specimens from the second part of the duodenum and from the bulb in 34 non-celiac subjects. The numbers of IELs in the villus tip and sides were counted and the quotient tip/side was calculated. HLA DQ2/DQ8 and serum antibodies against transglutaminase were analysed.ResultsThe mean number of IELs per 100 enterocytes (95% CI) in specimens was 14.7 (11.8-17.6) in the bulb, and 21.2 (17.0-25.5) in the second part of the duodenum (p<0.01). There was no difference in IEL count or distribution comparing patients carrying or lacking HLA DQ2/DQ8.ConclusionsIEL count in non-celiac, HLA DQ2/DQ8 positive or negative patients is significantly lower in the bulb than in the second part of the duodenum. These findings implicate that the site of biopsy should be taken into account when considering duodenal lymphocytosis.

Littoral Cell Angioma in a Patient with Crohn’s Disease

Littoral cell angioma is a rare vascular tumor of the spleen. The pathogenesis is unknown but the lesion is associated with several malignancies and immunological disorders. The diagnosis requires histopathological examination. The malignant potential of this lesion is unknown, which is why splenectomy is recommend for all cases. Symptomatic cases generally suffer from hypersplenism and pyrexia. A previously healthy 20-year-old female was diagnosed with colonic Crohns disease; as part of the work-up a magnetic resonance enterography was performed which showed multiple signal changes of the spleen. The patient reported chronic abdominal pain in the left upper quadrant, malaise, and fever. The unknown splenic lesions prompted a laparoscopic splenectomy; pathology revealed a littoral cell angioma. The abdominal pain and malaise remitted but the fever persisted one year despite adequate treatment of the patients Crohns disease. Littoral cell angioma is associated with immune-dysregulation including Crohns disease with several reported cases. Signs and symptoms of hypersplenism and splenic lesions on imaging should raise suspicion of littoral cell angioma in patients with Crohns disease. Magnetic resonance enterography to assess disease severity in Crohns disease may provide an opportunity to study the prevalence and natural history of this rare splenic tumor.

A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia.

Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world. The complete natural history of NAFLD is unknown because few high‐quality follow‐up studies have been conducted. Our aim was to find variables predicting disease severity through an extended follow‐up with serial biopsies. In a prospective cohort study, 129 patients who enrolled between 1988 and 1993 were asked to participate in a follow‐up study on two occasions; biochemical, clinical, and histologic data were documented. The mean time between biopsies was 13.7 (±1.7) and 9.3 (±1.0) years, respectively. At the end of the study period, 12 patients (9.3%) had developed end‐stage liver disease and 34% had advanced fibrosis. Out of the 113 patients with baseline low fibrosis (<3), 16% developed advanced fibrosis. Fibrosis progression did not differ among the different stages of baseline fibrosis (P = 0.374). Fifty‐six patients (43%) had isolated steatosis, of whom 9% developed advanced fibrosis (3 patients with biopsy‐proven fibrosis stage F3‐F4 and 2 patients with end‐stage liver disease). Fibrosis stage, ballooning, and diabetes were more common in patients who developed end‐stage liver disease; however, there were no baseline clinical, histologic, or biochemical variables that predicted clinical significant disease progression. Conclusion: NAFLD is a highly heterogeneous disease, and it is surprisingly hard to predict fibrosis progression. Given enough time, NAFLD seems to have a more dismal prognosis then previously reported, with 16% of patients with fibrosis stage <3 developing advanced fibrosis and 9.3% showing signs of end‐stage liver disease. (Hepatology Communications 2018;2:199–210)

How familiar are we with decision-making concerning the treatment of perforation after endoscopic mucosal resection (EMR) in the colon? A case report

Background and study aims  We describe a case of perforation after colonic endoscopic mucosal resection (EMR) that was treated conservatively. We would like to highlight the importance of decision-making mainly based on the endoscopists point of view in combination with the surgical consultation. Although the radiological imaging is always needed, it cannot solely lead to a decision for operation. Intraperitoneal gas in computed tomography is not always associated with a hole in the endoscopic field and could be possibly explained from a “balloon” phenomenon. The amount of extraluminal air after an EMR does not correlate reciprocally with patients pain after the procedure. Even though perforation is a radiological diagnosis and endoscopists should be aware of the common post-EMR radiological findings, the surgical examination is mandatory and should be coupled with the endoscopic opinion in order to guide appropriately the treatment in patients with acute pain.

Development of Serum Marker Models to Increase Diagnostic Accuracy of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: The New LINKI Algorithm Compared with Established Algorithms

Background and Aim Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms. Methods We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, King´s score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC). Results Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89. Conclusion The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.