Novel Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome due to Insulin Therapy

Abstract

Patient: Male, 67Final Diagnosis: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndromeSymptoms: Bilateral wrist swellingMedication: —Clinical Procedure: —Specialty: RheumatologyObjective:Unusual or unexpected effect of treatmentBackground:Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare clinical entity characterized by the sudden onset of inflammatory arthritis and marked pitting edema on upper and lower extremities. RS3PE is considered a rheumatic process distinct from rheumatoid arthritis, which may occasionally represent a paraneoplastic syndrome.Case Report:Herein, we describe a rare case of RS3PE associated with insulin therapy in a patient with no evidence of underlying malignancy.Conclusions:To the best of our knowledge, this is the first case report of RS3PE associated with insulin therapy. Physicians should look at the introduction of drugs as possible triggers for the development of RS3PE.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema in a Patient with Diabetes Mellitus Receiving Saxagliptin

“…2 The drugs reported in relation with RS3PE are insulin, DPP-4 inhibitors, rifampicin and nivolimab. [4][5][6] In the present case the clinical presentation and disease course of RS3PE due to saxagliptin showed a course similar to those related to the other etiologies but with the onset of disease at young age. Yamauchi et al reported two diabetic patients who developed RS3PE while taking DPP-4 inhibitors.…”

“…Most cases of RS3PE syndrome are idiopathic, although the syndrome has been associated with malignancy, rheumatologic diseases and some drugs. [2][3][4][5][6] In a meta-analysis evaluating 331 cases of RS3PE, it was shown that the relation of RS3PE with malignancy and rheumatologic diseases were 16.31% and 6.65% respectively. 2 The drugs reported in relation with RS3PE are insulin, DPP-4 inhibitors, rifampicin and nivolimab.…”

“…Except treatment with DPP-4 inhibitors, in diabetic patients, RS3PE was reported in association with insulin treatment and diabetes itself. 4,7,8 Oyama reported four patients with type 2 diabetes who developed RS3PE syndrome but among these patients there was a history of malignancy in two of the patients. 8 Sakoda desribed a patient at age of 59 who developed type 1 diabetes mellitus and RS3PE syndrome simultaneously.…”

“…Mainali and colleagues reported RS3PE syndrome associated with insulin therapy, regardless of its type. 4 DPP-4 enzyme, also known as a lymphocyte cell surface protein CD26, is an enzyme that degrades numerous peptides and plays a potential role in modulating immune system especially inhibiting proliferation of T cell and cytokine production. 9,10 Prolonged inhibition of DPP-4 by DPP-4inhibitors may influence immune system in different ways.…”

“…1,2 RS3PE is reported to be seen secondarily to malignancy, several disorders or drugs. [2][3][4][5][6] In the literature, we encountered two cases of RS3PE syndrome that are related with the use of DPP-4 inhibitor medication (sitagliptine and vildagliptine). 6 Saxagliptin is a relatively novel DPP-4 inhibitor and this is the first case report of the RS3PE in a patient receiving saxagliptin treatment.…”