Extraintestinal manifestations of gastroenterological disease in children: the gut–everywhere axis

Extraintestinal manifestations (EIMs) of gastrointestinal (GI) diseases are numerous and fascinating. They can affect almost any organ in the body and are caused by various mechanisms. Over the last decade the awareness of the ability of the gut to effect other parts of the body has become more widespread, the “gut–brain axis” being a powerful example. However, there are many different gut axes including lesser-known connections, such as the gut–liver axis, the gut–skin axis, the gut–joint axis, the gut–eye axis, the gut–immune axis and the gut–lung axis. The gut–skin, gut–joint and gut–eye axes are particularly interesting and known for their relationship with the EIMs seen in coeliac disease (CD) and inflammatory bowel disease (IBD). Some EIMs relate directly to GI disease activity and effective treatment of the intestinal disease will lead to a resolution of the EIMs. However, some EIMs, for example in IBD, occur independently of disease activity. The exact mechanisms and pathogenesis of EIMs is not fully understood. In this article we will briefly review and discuss the EIMs associated with coeliac disease and IBD. We will also describe non-gut symptoms and signs seen in other less common GI diseases such as congenital enteropathies and intestinal lymphangiectasia. This review will equip paediatricians and other health care professionals with the knowledge needed to identify EIMs in children with GI disease.