RESUMO
Introduction: We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome following administration of the ChAdOx1-S/nCoV-19 [recombinant] vaccine, suggesting a possible causal link. Case Description: A 72-year-old man presented to his general practitioner with swollen, oedematous hands and legs 2 weeks after receiving a coronavirus vaccine. He had raised inflammatory markers but remained systemically well. He was initially presumed to have cellulitis, but his symptoms persisted despite several courses of antibiotics. Deep vein thromboses, cardiac failure, renal failure and hypoalbuminaemia were ruled out. Upon Rheumatology review, he was diagnosed as having RS3PE syndrome with the Covid vaccine suspected of being an immunogenic trigger. Following initiation of steroid therapy, his symptoms improved dramatically, as is characteristic of RS3PE syndrome. Discussion: The pathophysiology of RS3PE is unclear. It is known to have various triggers and associations including infections, certain vaccines and malignancy. This case highlights that a coronavirus vaccine (ChAdOx1-S/nCoV-19 [recombinant] vaccine) is also a possible trigger. Factors that make the diagnosis likely include an acute onset of symptoms including pitting oedema in a typical distribution, age above 50, and unremarkable autoimmune serology. Other learning points from this case include the importance of antibiotic stewardship and the need to explore non-infectious causes of illness when antibiotics do not improve symptoms. Conclusion: The ChAdOx1-S/nCoV-19 [recombinant] vaccine is a possible trigger of RS3PE. However, the benefits of vaccines against coronavirus outweigh the risks in the majority of patients. LEARNING POINTS: This case demonstrates a possible link between the ChAdOx1-S/nCoV-19 [recombinant] vaccine and autoimmune conditions such as RS3PE.It is important to consider alternative diagnoses when antibiotic regimes fail to work.A barrier to accurate diagnosis includes an episodic approach, where a patient presents to multiple clinicians acutely rather than having a long-term, continuous relationship with a single multi-disciplinary team, where response to treatment can be monitored.
RESUMO
Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18-50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93-166]) and CT-proET-1 (ppET-1[169-212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses.