The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty-e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.

Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease: study protocol for a randomized controlled trial.

BACKGROUND: Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse, alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the cornerstone of alcoholic liver disease treatment; however, this approach is hampered by frequent relapse and lack of specific therapy for treating advanced cases of liver disease. In the present study, we hypothesized that gut microbiota drive the development of liver fibrosis and that modulation of gut microbiota with the gut-selective, nonabsorbable antibiotic rifaximin attenuates alcoholic liver fibrosis. METHODS/DESIGN: Our double-blind, placebo-controlled trial will include 136 participants with biopsy-verified alcoholic fibrosis (Ishak liver fibrosis score of 1-4). Participants are randomized 1:1 to receive placebo or 550 mg of rifaximin twice daily for 18 months. A liver biopsy will be performed at the end of the treatment period to evaluate the effect of drug treatment on liver fibrosis. Stool, urine, and saliva specimens will be collected before treatment begins, at 1 month, and at the end of the treatment period. Fecal samples are used for microbiome deep sequencing. Changes in microbiome composition are compared before and after the trial medication period and linked to changes in liver fibrosis. DISCUSSION: This is the first clinical trial to evaluate the effect of gut microbiota on liver fibrosis in humans. If gut microbiota are an important promoter of alcoholic liver disease, current results may open new therapeutic avenues and revolutionize the current understanding of chronic liver diseases. TRIAL REGISTRATION: EudraCT, 2014-001856-51 . Registered on 16 August 2014.

[Mastocytosis]. / Mastocytose.

Mastocytosis is a heterogeneous disease with an increased number and activation of mast cells. Subtypes range from benign to rare aggressive forms, and the disease may affect people of all ages. The pathogenesis involves mutations in the KIT gene in both children and adult patients. Estimated prevalence is one per 10,000, but the disease is very likely underdiagnosed. The diagnosis may be challenging and patients may present to several medical specialties. This article presents an overview of clinical signs and symptoms as well as a diagnostic algorithm and treatment options of mastocytosis.

Multidisciplinary Management of Mastocytosis: Nordic Expert Group Consensus.

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.

Targeting the gut-liver axis in cirrhosis: antibiotics and non-selective ß-blockers.

The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective ß-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses the issue of pharmacological treatment of cirrhosis and portal hypertension with antibiotics and NSBB. We discuss their mechanism of action and suggest that combining the two treatment modalities could potentially reduce the risk of complications.

Barrett's esophagus. Diagnosis, follow-up and treatment.

Barrett's Esophagus (BE) is a premalignant condition in the esophagus. Esophageal adenocarcinomas have the fastest increase of incidence of all solid tumors in the western world. BE is defined as areas with macroscopic visible columnar epithelium and intestinal metaplasia oral of the anatomical gastroesophageal junction. The extent of the endoscopic findings is described by the Prague classification. The metaplasia is histologically confirmed by the presence of intestinal metaplasia. The diagnosis of BE can only be made by a combined macroscopic and microscopic examination. The histological description should include evaluation of dysplasia, and if present it should be classified as low or high grade dysplasia. All patients are offered relevant antireflux treatment with PPI or surgery. Ablation or mucosal resection of metaplastic epithelia with or without low grade dysplasia is experimental and it is not recommended outside controlled studies. Treatment of high grade dysplasia and carcinoma in situ is handled in departments treating esophageal cancer. Follow-up with endoscopy and biopsy can be offered. Follow-up endoscopy with biopsy can only be recommended after thorough information to the patients, as evidence for the value is scarce.

Ulcerating and stenosing enteropathy treated with misoprostol: a case report with analysis of prostaglandin metabolism.

A case of a 40-year-old man with chronic anaemia because of nonspecific ulcerating and stenosing enteropathy is presented. The diagnosis was made on the basis of capsule endoscopy, histology of resected ileum and no use of NSAIDs. He showed a clinical response to treatment with misoprostol, and therefore, he was investigated for a possible impairment in eicosanoid biosynthesis compared with healthy controls. No deficient synthesis of prostacyclin, prostaglandin E2 and thromboxane was found on examination of metabolites in blood and urine. This suggests a normal release of arachidonic acid from phospholipids. Ex-vivo cyclooxygenase (COX) assays showed normal COX-1 and COX-2 activities. The clinical response to treatment with the prostaglandin E1 analogue misoprostol suggests a defective prostaglandin E synthesis in the intestinal mucosa.

[HELLP in the second trimester in a patient with antiphospholipid syndrome]. / HELLP kan ses i andet trimester ved antifosfolipidsyndrom.

The syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP) is estimated to occur in 0.01-0.2% of pregnancies and is considered a severe form of preeclampsia. It is associated with considerable risk of maternal and foetal mortality. HELLP syndrome associated with antiphospholipid syndrome is known to occur early in the pregnancy. We report a case of severe HELLP syndrome complicated by multiple hepatic infarctions and portal vein thrombosis in the second trimester in a patient with antiphospholipid syndrome.

[Protein-losing enteropathy caused by a thoracic cyst]. / Proteintabende enteropati forårsaget af torakal cyste.

A case of gastrointestinal protein loss in a 58-year-old man presenting with peripheral oedema and low levels of serum proteins is presented. Measurement of gastrointestinal protein loss with 111Indium-labelled transferrin showed a protein loss of 12.5% over 96 hours. Capsule endoscopy showed villous lymphangiectasia and it was assumed that the protein loss was secondary to a large left-sided thoracic cyst obstructing the thoracic lymph drainage. The patient improved following surgical removal of the cyst.

[Liver biopsy in liver patients with coagulopathy]. / Leverbiopsi hos leverpatienter med koagulopati.

The risk of severe bleeding after liver biopsy is estimated to be 1:12,000 in patients with near normal coagulation (INR < 1,5 and platelet count > 60 billion /l). Beyond these limits, the risk is higher, but still uncertain. The Danish guidelines require INR > 1.5, platelet count < 40 billion /l and normal APTT. In some instances the risk of not knowing the histology is so high that a biopsy is considered even with a more disturbed coagulation. Vitamin K, freshly frozen plasma and recombinant activated factor VII may reduce the risk of bleeding in specific situations, but no firm recommendations can be given.

[Non-cirrhotic intrahepatic portal hypertension]. / Noncirrotisk intrahepatisk portal hypertension.

Non-cirrhotic intrahepatic portal hypertension is characterized by portal hypertension in the absence of liver cirrhosis or portal vein thrombosis. The disease is common in the East and rarely seen in the West. Two cases with oesophageal varices are described. The histopathology is heterogeneous but includes vascular lesions and portal fibrosis. Patient management follows the current recommendations for variceal bleeding.

Economic evaluation of empirical antisecretory therapy versus Helicobacter pylori test for management of dyspepsia: a randomized trial in primary care.

OBJECTIVES: An economic evaluation was performed of empirical antisecretory therapy versus test for Helicobacter pylori in the management of dyspepsia patients presenting in primary care. METHODS: A randomized trial in 106 general practices in the County of Funen, Denmark, was designed to include prospective collection of clinical outcome measures and resource utilization data. Dyspepsia patients (n = 722) presenting in general practice with more than 2 weeks of epigastric pain or discomfort were managed according to one of three initial management strategies: (i) empirical antisecretory therapy, (ii) testing for Helicobacter pylori, or (iii) empirical antisecretory therapy, followed by Helicobacter pylori testing if symptoms improved. Cost-effectiveness and incremental cost-effectiveness ratios of the strategies were determined. RESULTS: The mean proportion of days without dyspeptic symptoms during the 1-year follow-up was 0.59 in the group treated with empirical antisecretory therapy, 0.57 in the H. pylori test-and-eradicate group, and 0.53 in the combination group. After 1 year, 23 percent, 26 percent, and 22 percent, respectively, were symptom-free. Applying the proportion of days without dyspeptic symptoms, the cost-effectiveness for empirical treatment, H. pylori test and the combination were 12,131 Danish kroner (DKK), 9,576 DKK, and 7,301 DKK, respectively. The incremental cost-effectiveness going from the combination strategy to empirical antisecretory treatment or H. pylori test alone was 54,783 DKK and 39,700 DKK per additional proportion of days without dyspeptic symptoms. CONCLUSIONS: Empirical antisecretory therapy confers a small insignificant benefit but costs more than strategies based on test for H. pylori and is probably not a cost-effective strategy for the management of dyspepsia in primary care.

Proton pump inhibitor or testing for Helicobacter pylori as the first step for patients presenting with dyspepsia? A cluster-randomized trial.

OBJECTIVES: The optimal approach for management of patients with dyspepsia has not been determined. The aim of this study was to compare the efficacy of three strategies for management of dyspepsia: empirical antisecretory therapy, testing for Helicobacter pylori (H. pylori), or a combination of the two. METHODS: Cluster-randomized trial in general practices. Initial treatment with proton pump inhibitor (PPI) was performed in 222 patients, H. pylori test-and-eradicate in 250 patients, and PPI followed by H. pylori-testing if symptoms improved in 250 patients. Symptoms, quality of life, patient satisfaction, and use of resources were recorded during a 1-yr follow-up. RESULTS: The prevalence of H. pylori infection was 24%. We found no difference among the three strategies (p=0.16) in terms of the proportion of days without dyspeptic symptoms. After 1 yr gastrointestinal symptom scores and quality-of-life scores had improved significantly and equally in the three groups (p<0.001), but no statistically significant differences were found among the groups. The mean use of endoscopies per patient after 1 yr was higher in the PPI group (0.36 [95% CI 0.30-0.43]) than in the test-and-eradicate group (0.28 [95% CI 0.23-0.34]) and the combination group (0.22 [95% CI 0.17-0.27]), p=0.02. H. pylori-positive patients given eradication therapy had more days without dyspeptic symptoms (p<0.001), used less antisecretory therapy (p<0.01), and were more satisfied (p<0.001) than H. pylori-negative patients. CONCLUSION: The strategies based on H. pylori test enjoyed similar symptom resolution, but reduced endoscopic workload and lower 1-yr total costs compared with empirical antisecretory therapy.