Joanne Lopes

Omalizumab in the treatment of eosinophilic esophagitis and food allergy

Omalizumab is currently used in severe asthma and has been tried in other allergic disorders. The authors report two patients with multiple food allergies and eosinophilic esophagitis on a very restrictive diet who have been treated with omalizumab, in order to improve food intolerance—the major distressing factor in their lives. The patients significantly improved in the reported symptoms. However, no improvement was seen regarding esophageal endoscopy and histology. Given the poor histological and endoscopy response, eosinophilic esophagitis persistence is unlikely to be IgE dependent. Omalizumab may improve the quality of life of patients with severe food allergy by improving symptoms, but it does not appear to change endoscopic and histological features of eosinophilic esophagitis in a short follow-up.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: A single center report of 8 cases

This article describes cases of anti-tumor necrosis factor (TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis (AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

BACKGROUND & AIMS The liver, being the major site of iron storage, is particularly exposed to the toxic effects of iron. Transcription factor NRF2 is critical for protecting the liver against disease by activating the transcription of genes encoding detoxification/antioxidant enzymes. We aimed to determine if the NRF2 pathway plays a significant role in the protection against hepatic iron overload. METHODS Wild-type and Nrf2(-/-) mouse primary hepatocytes were incubated with ferric ammonium citrate. Wild-type and Nrf2(-/-) mice were fed standard rodent chow or iron-rich diet for 2weeks, with or without daily injection of the antioxidant mito-TEMPOL. RESULTS In mouse hepatocytes, iron induced the nuclear translocation of NRF2 and the expression of cytoprotective genes in an NRF2-dependent manner. Moreover, Nrf2(-/-) hepatocytes were highly susceptible to iron-induced cell death. Wild-type and Nrf2(-/-) mice fed iron-rich diet accumulated similar amounts of iron in the liver and were equally able to increase the expression of hepatic hepcidin and ferritin. Nevertheless, in Nrf2-null mice the iron loading resulted in progressive liver injury, ranging from mild confluent necrosis to severe necroinflammatory lesions. Hepatocytic cell death was associated with gross ultrastructural damage to the mitochondria. Notably, liver injury was prevented in iron-fed animals that received mito-TEMPOL. CONCLUSIONS NRF2 protects the mouse liver against the toxicity of dietary iron overload by preventing hepatocytic cell death. We identify NRF2 as a potential modifier of liver disease in iron overload pathology and show the beneficial effect of the antioxidant mito-TEMPOL in a mouse model of dietary iron-induced liver injury.

Adenoma–carcinoma sequence in intrahepatic cholangiocarcinoma

INTRODUCTION Cholangiocarcinoma is a rare tumor but recent data report a worldwide increase in incidence and mortality. There are several risk factors associated with cholangiocarcinoma, and chronic inflammation of billiary tree seems to be implied in the cholangiocarcinogenesis, but little is known about this process. PRESENTATION OF CASE We present a 56-year-old female with a bile duct adenoma incidentally discovered in the follow up of breast cancer that 18 months later progress to intrahepatic cholangiocarcinoma. DISCUSSION This is a rare presentation of intrahepatic cholangiocarcinoma that suggests the classic adenoma-carcinoma sequence in cholangiocarcinogenesis. Furthermore this case gives rise to some questions about the possible common ground on intrahepatic cholangiocarcinoma and breast cancer. CONCLUSION Cholangiocarcinogenesis is a complex multi-step mechanism and further investigations are needed to fully understand this process.

Metastatic cutaneous Crohn's disease of the face: a case report and review of the literature

Metastatic cutaneous Crohns disease is one of the most uncommon cutaneous extraintestinal manifestations. The face is the rarest location, with only eight cases described in the literature. We report a rare case of a young man with Crohns disease and two granulomatous lesions on the face in a nodular form. To the best of our knowledge, this is the first report of metastatic Crohns disease of the forehead with the features of nodules. A review of the literature concerning metastatic Crohns disease is also provided.

Accuracy of Faecal Calprotectin and Neutrophil Gelatinase B-associated Lipocalin in Evaluating Subclinical Inflammation in UlceRaTIVE Colitis-the ACERTIVE study.

Background and Aims Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. Methods This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. Results Macroscopic lesions [i.e. endoscopic Mayo score ≥1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 μg/g for faecal calprotectin and 12 μg/g for neutrophil gelatinase B-associated lipocalin were proposed. Conclusions Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.

Tactoid body features in a Schwann cell hamartoma of colonic mucosa.

Background. Mesenchymal colorectal polyps are uncommon lesions, particularly those of neurogenic origin. We describe a mucosal Schwann cell hamartoma of the colon with tactoid features, so far reported in peripheral nerve sheath tumours, and address its differential diagnosis and clinical implications. Case presentation. A 72-year-old man underwent screening colonoscopy that presented a 5-mm polyp on distal sigmoid. Histologically, it displayed a lesion in the lamina propria comprising oval structures with tactoid features and bland spindle cells, entrapping adjacent crypts. No ganglion cells were seen. Spindle cells expressed only S-100 protein and vimentin. Discussion. Mucosal Schwann cell hamartoma was recently recognized as distinct from common (submucosal) colorectal Schwannomas and so far not associated to inherited syndromes. Thus, it should be considered in the differential diagnosis of look-alike lesions (eg, ganglioneuroma, neuroma, and neurofibroma) that may occur in the setting of inherited syndromes such as Cowden syndrome, multiple endocrine neoplasia-2B, and type 1 neurofibromatosis.

Thalidomide-induced acute cholestatic hepatitis: Case report and review of the literature

Drug-induced liver injury (DILI) is a leading cause of liver failure and an important safety issue in drug development. Thalidomide is nowadays used for the treatment of several conditions including multiple myeloma (MM). Several adverse effects have been described but liver toxicity was seldom reported. We describe a case of thalidomide-induced hepatitis in a man treated for MM. The clinical setting and temporal association between the start of the drug and liver injury allowed the assumption of the causative role of thalidomide. As its clinical indications expand we wish to increase awareness of a new potential side effect of thalidomide. A short review on thalidomide-induced liver injury is also presented.

Familial Occurrence of Nodular Regenerative Hyperplasia of the Liver

To the Editor: A 42-year-old woman with asthenia and weight loss was diagnosed with pancytopenia and splenomegaly in 1996, without other relevant findings in blood tests or abdominal ultrasound. She was submitted to splenectomy and surgical liver biopsy. Histology revealed a fibrocongestive spleen, and a liver biopsy was reported as having a normal structure. After splenectomy, there was a complete normalization of the blood parameters.

Clinical performance of an infliximab rapid quantification assay

Background: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. Methods: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. Results: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman’s rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791–0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g. Conclusions: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.