Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab

A new articular syndrome described as immunrelated side effect of immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced melanoma but are responsible for immune-related toxicity. We report a case of remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab.

A 80 year-old man with stage IV BRAF-wild type and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every 2 weeks. At week 4, before the 3rd infusion, he presented with inflammatory arthralgia, synovitis of proximal interphalangeal, wrist and ankle joints, and edema of both hands and forearms. Laboratory tests showed inflammatory syndrome (CRP = 8.4mg/dL), negative rheumatoid factor, and anti-CCP antibodies. Radiographs did not show any joint erosion but joint ultrasound displayed intra-articular effusion and tenosynovitis. PET/CT performed 6 and 3 months before treatment for melanoma work-up showed an isolated hypermetabolism of the shoulder girdle. The diagnosis of RS3PE was retained. A systemic corticosteroid treatment (0.5mg/kg/d) was initiated; nivolumab was hold during 4 weeks leading to remission of clinical symptoms within 10 days, CRP level normalization and without relapse when nivolumab was resumed. Corticosteroids were progressively tapered and stopped after 9 months. After 5 months, anti-PD1 was definitively stopped because of disease progression.

With this atypical case, clinicians should remain alert on a whole range of autoimmune diseases susceptible to be induced.