Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-articular involvement

Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.