Seronegative rheumatoid arthritis: when blood tests are negative

Rheumatoid arthritis (RA) is an autoimmune disease. The NHS explains that the immune system, which usually fights infection, attacks the cells that line the joints by mistake, making the joints swollen, stiff and painful, and that over time this can damage the joints, cartilage and nearby bone.

Doctors use blood tests as part of the diagnosis. NRAS describes rheumatoid factor as one sign of RA but not a conclusive one, because about 30% of people with RA do not have it and some people with other conditions do. Anti-CCP antibody is described as more specific for RA. The word seronegative is used when these antibody tests are negative in someone who otherwise has the picture of RA, meaning inflamed joints in a typical pattern.

Being seronegative therefore says something about the blood, not about whether the joints are inflamed. The pain, swelling and stiffness are real, the joint lining is inflamed, and the same principles of early assessment and treatment apply. The sources used for this page do not compare outcomes between antibody-positive and antibody-negative RA, so questions about your own outlook are best put to your rheumatologist.

The NHS says RA is a long-term condition that causes pain, swelling and stiffness in the joints, usually in the hands, feet and wrists, with periods of worse symptoms called flares. NRAS lists the key symptoms to be aware of.

• Pain, swelling and possibly redness around the joints, with the hands and feet often affected first.

• Stiffness when you get up in the morning or after sitting for a while, lasting more than 30 minutes with no other obvious cause.

• Fatigue that is more than normal tiredness.

• Both sides of the body often affected in a similar way, tending to start with small joints of the hands and feet such as the knuckles.

• Less commonly, rheumatoid nodules, lumps under the skin over joints that are easily knocked, which NRAS says affect around 20% of people with RA.

The NHS says to see a GP if you think you have symptoms of RA, so they can try to identify the underlying cause. NRAS adds that the sooner RA is diagnosed and treated, the better the long-term outcomes are likely to be.

NICE CKS advise that all people suspected of having RA should be referred for specialist assessment to confirm the diagnosis, with referral within 3 working days if the small joints of the hands or feet are affected, more than one joint is affected or there has been a delay of 3 months or longer between onset and seeking advice. A negative antibody result should not delay a referral. A hot, swollen, single joint with fever is a different matter: NICE CKS list excluding septic arthritis as part of managing a flare, so a very hot, red joint with feeling unwell needs urgent assessment through NHS 111 or A&E.

NRAS explains that RA can be tricky to diagnose, there is no single test, and a rheumatologist takes several things into account. Blood tests can show signs of inflammation (a raised ESR or CRP). Rheumatoid factor and anti-CCP tests give additional information but do not tell the whole story.

There is no cure, but treatment is effective. The NHS says early diagnosis and appropriate treatment enable many people to have periods of months or even years between flares, and to lead full lives and continue regular employment. NICE CKS describe specialist treatment using a treat-to-target strategy, with the aim of remission or low disease activity, usually starting with a conventional disease-modifying anti-rheumatic drug (DMARD) such as methotrexate, leflunomide or sulfasalazine, and with short-term steroids as a bridge while the DMARD takes effect.

If the disease remains active, additional DMARDs may be combined in a step-up approach, and biological drugs may be offered in combination with methotrexate where severe disease has not responded. NRAS also lists JAK inhibitors, tablets that are described as similarly highly effective as biologic drugs, and notes that DMARDs take several weeks to work. It says that once joints are damaged this cannot be reversed with medication, so the aim is to prevent damage before it occurs.

Supportive treatment matters too. The NHS lists physiotherapy and occupational therapy to keep you mobile and manage daily activities, and surgery to correct joint problems that develop. NICE CKS advise a surgical opinion where pain, function, deformity or synovitis persist despite optimal non-surgical management, or where tendon rupture or nerve compression occurs.

The NHS says RA can lead to other conditions including carpal tunnel syndrome, inflammation of other areas such as the lungs, heart and eyes, and an increased risk of heart attack and stroke, and that keeping RA well controlled helps reduce those risks. NICE CKS list cardiovascular disease, osteoporosis, anaemia and infection among complications and comorbidities.

NRAS says you will have blood tests at intervals during treatment, which monitor how active the RA is, using ESR and CRP, and look out for early warnings of drug side effects, including checks on kidney and liver function. Smoking makes RA more likely and, according to NRAS, makes the disease more aggressive when combined with certain genes, so stopping smoking is part of the plan.

On the NHS the route is GP, then a rheumatology team, with a named nurse specialist and regular blood monitoring that can be shared with the GP. Some people choose a private rheumatologist to be seen sooner. The tests, drugs and monitoring are the same in principle, and many people move between the two. Whichever route you use, ask which results you should keep, and who reviews the monitoring blood tests.