Peripheral arthritis is one of the most common manifestations of articular syndrome, not always associated with rheumatic diseases. Determination of its nosological affiliation and rational therapy at an early stage (early arthritis) present a complex clinical and diagnostic problem requiring an interdisciplinary approach. The review presents the differential diagnosis of early arthritis in diseases of the gastrointestinal tract such as inflammatory bowel disease, celiac disease, PPP syndrome (Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome), etc., manifested by similar clinical symptoms with rheumatic diseases such as early rheumatoid arthritis and spondylitis. Most of the immuno-inflammatory diseases presented in the review are multisystemic and heterogeneous in clinical symptoms, course and outcomes. Therefore, the diagnostic process, especially in case of early arthritis with typical multisystem involvement, is comprehensive and cognitive in nature and requires the synthesis of many data that are usually not taken into account in a simple algorithm based on a set of classification criteria.