RS3PE syndrome: Autoinflammatory features of a rare disorder

Abstract

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome was first described by McCarty in 1985 and is characterized by pitting oedema and an acute symmetrical synovitis of small joints. Self-directed inflammation in autoimmune disorders is caused by an abnormal activation of the adaptive immune system, while in autoinflammatory disorders, it is due to aberrant activation of the innate immune system without autoantibodies or autoreactive T cells. The role of autoimmunity in the pathogenesis of RS3PE syndrome is suggested by possible associations with some autoimmune diseases and human leukocyte antigen (HLA) haplotypes. However, several other features point to a possible role of autoinflammation in RS3PE syndrome. In this review, the relative contributions of both innate and adaptive immune systems to the pathogenesis of RS3PE syndrome are discussed.

Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome with Pembrolizumab for Lung Squamous Cell Carcinoma

“…Recurrence of malignancy or other systemic diseases that can cause RS3PE was not observed in the present case. In addition, some drugs can cause RS3PE (14). Indeed, dipeptidyl peptidase-4 (DPP4) inhibitors are risk factors for RS3 PE (18), and the effect of DPP4 inhibitors on the development of RS3PE in this case cannot be completely ruled out, as he had been taking teneligliptin; however, RS3PE symptoms occurred after ICI administration and remained improved after prednisolone treatment even with the continuous use of DPP4 inhibitors.…”

“…Notably, pembrolizumab-induced irAEs manifested as RS 3PE in this case. RS3PE etiology includes idiopathic and secondary comorbidities of other diseases and drugs (14). Malignancy (20%-54%) is the most common cause (15,16), while other diseases include systemic lupus erythematosus, gout, Sjögren's syndrome, polyarteritis nodosa, ankylosing spondylitis, sarcoidosis, amyloidosis, relapsing polychondritis, bronchiolitis obliterans, and organizing pneumonia (17).…”

Polymyalgia Rheumatica Evolved into RS3PE Syndrome. What is the Culprit: Idiopathic or Secondary, Following mRNA-Based COVID-19 Vaccines? A Case Report and Brief Review of the Literature

“…With regards to a similar English report relating to the monovalent Moderna vaccine, up to the same date, the RS3PE syndrome did not appear: only 22 cases of polymyalgia rheumatica were indicated out of 17,072 reports relating to the "Muscle & tissue disorders" group, out of a total of 47,045 Yellow cards reports [31]. According to some researchers both PMR and RS3PE, caused by mRNA anti-COVID-19 vaccines, can fall into the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) also called Shoenfeld syndrome [32][33][34].…”

A Case Report of Remitting Seronegative Symmetrical Synovitis With Pitting Edema Causing Severe Anemia, Acute Progressive Dementia, and Chronic Eczema in an Older Female

“…Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a type of seronegative arthritis more common in elderly males, named for its characteristics: (1) a favorable prognosis (Remitting), (2) negative for rheumatoid factor (Seronegative), (3) symmetrical in presentation (Symmetrical), and (4) synovitis with pitting edema on the dorsum of the hands and feet (Synovitis with Pitting Edema) [1]. The etiology is unknown, but there have been reports of approximately half of the cases being positive for the human leukocyte antigen (HLA)-B7, suggesting immune system involvement, and reports implicating HLA-CW7 and HLADQW2 [2]. Typical manifestations include sudden onset of symmetrical arthritis and synovitis of the fingers and hands, with pitting edema, though elbow, shoulder, knee, and foot involvement can also occur [3].…”