Unmet Needs in IBD: the Case of Fatigue.

Fatigue is a highly prevalent but relatively ignored problem in IBD patients. It is one of the most burdensome symptoms to the patient with an important impact on the quality of life. Therefore, fatigue is a highly relevant patient-reported outcome that should be included not only in disease activity measurement but also in the endpoints of clinical trials in IBD. However, most of the currently available scoring systems to quantify fatigue are not specifically designed for patients with IBD and none of them has undergone a complete validation process for IBD-related fatigue. Fatigue is more prevalent in patients with active disease and may improve or disappear when remission is reached. Far more complex is the persistence or onset of fatigue in quiescent IBD which presents in up to 40% of the patients. In this subgroup of patients, fatigue can be related to smoldering systemic inflammation, a poor sleep quality, anemia, nutritional deficiencies, or comorbidities. In most cases, however, no direct cause can be identified. The lack of knowledge on the mechanisms that drive fatigue in IBD hamper the development of specific drugs to treat the condition and only psychological support can be offered to the patient. Rodent models are indispensable to increase our understanding of the molecular pathways that lead to fatigue in chronic intestinal inflammation, and to develop novel therapies.