RS3PE syndrome: swollen hands and feet with sudden arthritis in older adults

RS3PE stands for remitting seronegative symmetrical synovitis with pitting oedema. Each part of the name describes a feature. Remitting means it tends to settle and often stays away; seronegative means that rheumatoid factor, the antibody found in many people with rheumatoid arthritis, is not present; symmetrical means both sides of the body are affected; synovitis is inflammation of the lining of joints and tendon sheaths; and pitting oedema means swelling that leaves a dent when pressed.

A 2008 case report from UK hospitals in the West Midlands describes it as a subset of acute-onset polyarthritis that mainly affects older people and predominantly males, with a clinical picture of acute-onset pitting oedema of the hands. The condition was first described in 1985, and the exact incidence and prevalence are not known.

The picture described in the case reports is of an acute onset, with painful swollen hands, stiff fingers and wrists, and swollen feet and ankles. Doctors may find swelling on the backs of the hands and feet and inflammation of the tendon sheaths. A 2025 case report notes that one patient had previously been diagnosed with carpal tunnel syndrome in both hands, a reminder that swollen wrists can mimic other conditions.

General symptoms such as low-grade fever, tiredness and reduced mobility can occur. The 2008 case report notes that fever and weakness can be non-specific signs of inflammation, but that other systemic signs, such as weight loss, loss of appetite and poor response to steroids, could point to a paraneoplastic cause.

There is no single test. The 2008 UK report cites proposed diagnostic criteria: bilateral pitting oedema of both hands, sudden onset of polyarthritis, age over 50 years and negative rheumatoid factor. Blood tests typically show raised inflammatory markers and sometimes mild anaemia with a negative rheumatoid factor; X-rays of the hands may show soft-tissue swelling, and the absence of erosions is described as classic.

Doctors also look for other causes of swollen hands, feet and ankles. The case report notes that evaluation of pedal oedema should rule out congestive heart failure, nephrotic syndrome and an underactive thyroid, and that the main differential is polymyalgia rheumatica, other considerations including rheumatoid arthritis, late-onset spondyloarthropathy and crystal arthritis. In the NHS this assessment is made by a GP and a rheumatologist, who may arrange blood tests, imaging and tests to look for malignancy where indicated. The case report notes that MRI studies suggest inflammation of the extensor tendon sheaths is the main lesion behind the swelling.

The NHS describes polymyalgia rheumatica (PMR) as causing pain and stiffness around the shoulders, neck and hips, with morning stiffness lasting longer than 45 minutes, and as mainly affecting people over 65, more often women. It is treated with prednisolone, usually for 12 months to 2 years. The NHS also warns that up to 1 in 5 people with PMR develop temporal arteritis, for which new headache, scalp tenderness, jaw pain or vision changes need immediate contact with a GP or NHS 111.

The 2008 case report states that RS3PE can be associated with both solid tumours, such as gastric and pancreatic cancers, and haematological malignancies, such as non-Hodgkin lymphoma. It says patients with idiopathic RS3PE show an excellent response to low-dose steroids compared with a poor response when RS3PE occurs with a neoplasm, and that the search for hidden malignancy is crucial in patients with prominent systemic symptoms who do not respond to steroids.

This does not mean that most people with RS3PE have cancer. Many have no underlying cause. It does explain why doctors may ask about weight loss, appetite and night sweats, examine carefully and may arrange further scans, and why follow-up after remission is advised. A 2025 report of a patient without cancer at diagnosis also emphasises the value of active screening and careful follow-up.

Low-dose corticosteroids, such as prednisolone, are the usual treatment. The 2008 case report describes a man who responded dramatically to prednisolone 7.5 mg daily, with complete resolution of signs and symptoms at 8 weeks on a tapering dose without flare-ups. The 2025 case report describes a patient treated with corticosteroids tapered over a year, whose symptoms recurred, requiring steroids to be reintroduced for a further two years, with complete and sustained remission.

Steroids have side effects, especially in older people who may already have osteoporosis, high blood pressure, diabetes or heart failure, as the 2008 report notes. They should not be stopped suddenly without medical advice. Your rheumatologist will guide the dose, the tapering and the monitoring for relapse.

See a GP promptly if you develop sudden swelling of the hands or feet with joint pain, particularly if you are over 50. Seek urgent help if swelling is in one leg only and painful (possible clot), or if you are breathless or have chest pain.