Assessment of extraintestinal manifestations in inflammatory bowel diseases: A systematic review and a proposed guide for clinical trials.

BACKGROUND AND AIMS: Extraintestinal manifestations are common in inflammatory bowel disease patients, although there are few data available on their diagnosis, management and follow-up. We systematically reviewed the literature evidence to evaluate tools and investigations used for the diagnosis and for the assessment of the treatment response in inflammatory bowel disease patients with extraintestinal manifestations. METHODS: We searched in PubMed, Embase and Web of Science from January 1999-December 2019 for all interventional and non-interventional studies published in English assessing diagnostic tools and investigations used in inflammatory bowel disease patients with extraintestinal manifestations. RESULTS: Forty-five studies (16 interventional and 29 non-interventional) were included in our systematic review, enrolling 7994 inflammatory bowel disease patients. The diagnostic assessment of extraintestinal manifestations was performed by dedicated specialists in a percentage of cases ranging from 60-100% depending on the specific condition. The clinical examination was the most frequent diagnostic strategy, accounting for 35 studies (77.8%). In patients with primary sclerosing cholangitis or rheumatological symptoms, biochemical and imaging tests were also performed. Anti-TNF agents were the most used biological drugs for the treatment of extraintestinal manifestations (20 studies, 44.4%), and the treatment response varied from 59.1% in axial spondyloarthritis to 88.9% in ocular manifestations. No benefit was detected in primary sclerosing cholangitis patients after treatment with biologics. CONCLUSIONS: In the clinical management of inflammatory bowel disease patients with extraintestinal manifestations the collaboration of dedicated specialists for diagnostic investigations and follow-up is key to ensure the best of care approach. However, international guidelines are needed to homogenise and standardise the assessment of extraintestinal manifestations.

Diagnostic tools in ocular allergy.

Ocular allergy (OA) includes a group of common and less frequent hypersensitivity disorders frequently misdiagnosed and not properly managed. The diagnosis of OA is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when identification of the specific allergen is required. To date, no specific test is available for the diagnosis of the whole spectrum of the different forms of OA. The lack of recommendations on diagnosis of OA is considered a medical need not only for allergists but also for ophthalmologists. This position paper aims to provide a comprehensive overview of the currently available tools for diagnosing OA to promote a common nomenclature and procedures to be used by different specialists. Questionnaires, sign and symptom grading scales, tests, and potential biomarkers for OA are reviewed. We also identified several unmet needs in the diagnostic tools to generate interest, increase understanding, and inspire further investigations. Tools, recommendations, and algorithms for the diagnosis of OA are proposed for use by both allergists and ophthalmologists. Several unmet needs in the diagnostic tools should be further improved by specific clinical research in OA.

Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management.

Abstract Extraintestinal manifestations occur rather frequently in inflammatory bowel disease (IBD), e.g. ulcerative colitis (UC) and Crohn's disease (CD). The present paper provides an overview of the epidemiology, clinical characteristics, diagnostic process, and management of rheumatic, metabolic, dermatologic (mucocutaneous), ophthalmologic, hepatobiliary, hematologic, thromboembolic, urinary tract, pulmonary, and pancreatic extraintestinal manifestations related to IBD. Articles were identified through search of the PubMed and Embase databases, the Cochrane Library, and the web sites of the European Agency for the Evaluation of Medicinal Products (EMEA) and the US Food and Drug Administration (FDA) (cut-off date October 2009). The search terms 'Crohn's disease', 'inflammatory bowel disease', or 'ulcerative colitis' were combined with the terms 'adalimumab', 'anemia', 'arthritis', 'bronchiectasis', 'bronchitis', 'cutaneous manifestations', 'erythema nodosum', 'extraintestinal manifestations', 'hyperhomocysteinemia', 'infliximab', 'iridocyclitis', 'lung disease', 'ocular manifestations', 'osteomalacia', 'pancreatitis', 'primary sclerosing cholangitis', 'renal stones', 'sulfasalazine', 'thromboembolism', and 'treatment'. The search was performed on English-language reviews, practical guidelines, letters, and editorials. Articles were selected based on their relevance, and additional papers were retrieved from their reference lists. Since some of the diseases discussed are uncommon, valid evidence of treatment was difficult to obtain, and epidemiologic data on the rarer forms of extraintestinal manifestations are scarce. However, updates on the pathophysiology and treatment regimens are given for each of these disorders. This paper offers a current review of original research papers and randomized clinical trials, if any, within the field and makes an attempt to point out practical guidelines for the diagnosis and treatment of various extraintestinal manifestations related to IBD.

HLA and eye disease: a synopsis.

Human leukocyte antigen (HLA) gene products have been implicated in the pathogenesis of an increasing number of eye diseases, mainly inflammatory in nature. This perspective reviews the current hypotheses for why HLA polymorphisms are associated with specific eye diseases. Statistical problems in studies involving HLA associations are discussed, and possible solutions outlined. The relevance of HLA testing in routine ophthalmic practice, its practical and cost implications is also assessed.