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Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome consisting of acute symmetrical tenosynovitis of the hands and wrists associated with pain and marked pitting edema of the dorsum of the hands or the feet. Persistent rheumatoid factor seronegativity and elevated acute phase reactants are the rule, while radiographic findings are characterized by the absence of bony erosions. The syndrome has occasionally been associated with a wide range of diseases including solid and hematological malignancies, polymyalgia rheumatica, and other inflammatory rheumatic diseases.Two patients with skin eruption on hands and feet associated with arthromyalgias have been investigated to confirm diagnosis of RS3PE and to detect comorbidities. A revision of all the possible medical conditions correlated to RS3PE has been performed.We report two cases of RS3PE associated with Parvovirus B19 infection/reactivation. There are very few reports on the association between RS3PE and infectious agents, and in only one case the syndrome has been correlated to parvovirus infection.We want to underline the importance for patients with RS3PE to be seen by dermatologists who should become familiar with this syndrome and remark that Parvovirus B19 infection may be a potential cause of RS3PE.