- Sarah Cole, 28, developed symptoms typical of rheumatoid arthritis
- Nurse, from Bristol UK, saw rheumatologist who gave her the blood test
- Again and again, her test came back negative
- Her specialist decided despite her results, Sarah did have RA
As Sarah Cole’s wedding day neared, she joked with her bridesmaids that she would be hobbling down the aisle on crutches.
‘It wasn’t funny, but I knew there was a real risk it might happen,’ says Sarah, now 27, a nurse, who lives in Bristol with her husband, Lee, 28, a hospital operating theatre assistant.
‘Ten months earlier I’d woken up with a swollen, stiff thumb and thought nothing of it, but within days the inflammation had spread all over my body affecting both hands, feet, shoulders, elbows and knees. I was racked with pain. My joints felt hot and looked swollen.
Sarah’s symptoms were typical of rheumatoid arthritis, an auto-immune disease in which the body attacks the lining of the joints, causing pain and disability.
Her GP referred her to a rheumatologist who gave her the standard blood test for rheumatoid factor, an antibody produced by the body when it attacks its own tissue. But Sarah’s test came back negative.
‘Although my specialist suspected rheumatoid arthritis, he wasn’t 100 per cent sure because of the blood test results.’
He adopted a watch-and-wait approach and called her back for repeat blood tests over the next few months, but the result was always the same.
‘It was frustrating to be left in limbo with no treatment, as I was in a lot of pain,’ says Sarah. ‘Some days I’d wake up and my hands would look like claws because my fingers were stiff and bent and it would hurt to lift my arms up because my shoulders were so painful. I couldn’t sleep because of the pain and felt exhausted.’
She was started on the standard rheumatoid arthritis treatment, the drug methotrexate and steroids, and within three months she was pain-free.
Her story is unusual, as awareness of seronegative rheumatoid arthritis is low among both the public and some doctors. In fact, it accounts for a third of the 600,000 people in the UK with rheumatoid arthritis.
However, the fact that it cannot be diagnosed with standard blood tests has led to it being ignored. Yet early diagnosis in all forms of the disease is important, as good control of symptoms with drugs in the first three months can prevent irreversible joint damage.
‘Being seen and treated as early as possible is so important because clinical trials have shown early aggressive treatment in the first few weeks after symptoms begin can improve outcomes,’ says Dr James Galloway, a clinical lecturer and honorary consultant rheumatologist at King’s College London.
‘One small trial at the University of Manchester even found that in some people, drugs can switch off the disease completely.’
The key difference with seronegative arthritis is it doesn’t produce the rheumatoid factor antibodies as the standard ‘seropositive’ form. ‘As a result the symptoms can be mistaken for overdoing it in the garden, carpal tunnel syndrome or even a menopausal symptom,’ says Ailsa Bosworth, chief executive of the National Rheumatoid Arthritis Society (NRAS).
Professor David Scott, chief medical adviser to the NRAS, explains that with rheumatoid arthritis, there are thousands of antibodies, proteins and white blood cells in the immune system that can attack the joint.
‘Just because you test negative for rheumatoid factor doesn’t mean you don’t have rheumatoid arthritis, and you can also have rheumatoid factor without having the condition,’ he says.
The classic symptoms of rheumatoid arthritis are pain, swelling and stiffness in the joints, most commonly starting in the small joints of the hands and feet, and affecting both sides of the body, usually with rapid onset. However, the other difficulty with detecting the seronegative form is that the symptoms can come on subtly and slowly, says Dr Galloway.
‘Patients might have flare-ups of swollen joints which seem to be get better on their own.
‘If symptoms are in the knee, for instance, it might look similar to a condition such as housemaid’s knee (swelling of the kneecap, common in those who kneel a lot).’
Rheumatoid arthritis of any kind is between two and four times more likely to affect women than men – the theory is that hormones play a part and symptoms start most commonly between 40 and 60, although it affects all age groups.
It’s thought environmental factors such as smoking, an infection or hormones can trigger it in those with certain genes.
Dr Louise Warburton, a GP who runs an NHS arthritis clinic in Telford, Shropshire, says doctors rely too much on blood tests to diagnose the condition.
‘We need to tell GPs not to delay referring to a specialist; it’s fine to do the blood tests, as the results may be useful later in secondary care, but make the referral based on symptoms, history and the presence of other inflammatory markers.’
Yet research by the universities of Oxford and Bath published last year, and involving 1,800 patients, found that nearly half – 800 patients – who tested negative for rheumatoid factor waited an extra 45 days to get a referral.
The warning signs for either form are joint swelling, particularly in the hands and feet, and early morning stiffness that lasts more than half an hour. Your hands will also hurt if they are squeezed.
Other possible symptoms include inflammation in other joints, including the knee, fatigue and a flu-like illness and general stiffness in the body. Pain is usually symmetrical, affecting both sides of the body, although it may not be initially.
Treatments include steroids to reduce inflammation during attacks and methotrexate and sulfasalazine – these are disease-modifying drugs that work on the immune system to stop inflammation before it occurs.
Other options include biologics, drugs that target certain proteins thought to be involved in inflammation (given intravenously or by injection). All treatments work for both seronegative and seropositive rheumatoid arthritis.
The proportion of rheumatoid arthritis patients who don’t take their drugs as prescribed
Dr Galloway says that while having seronegative means your disease will not usually be as rapid and aggressive as other forms of rheumatoid arthritis, the flip side is that some of the usual treatments may not work as well for it.
‘For example, the drug rituximab works by blocking certain antibodies that attack joints – but in seronegative RA it doesn’t work that well because it may not just be antibodies attacking the joint but other parts of the immune system.’
Dr Martin Lee, a consultant rheumatologist at the Freeman Hospital in Newcastle, says the situation is improving, as there are now around a 100 or so clinics around the UK where patients with ‘inflammatory’ arthritis can be seen and investigated within a few weeks of referral.
‘It’s true that in primary care there is still an over-reliance on blood tests and while they are useful, you can get both false positive and false negative results, so it’s best to refer as soon as possible,’ says Dr Lee.
‘At inflammatory arthritis clinics we’ll do blood tests, but also examinations, X-rays, ultrasound and MRI scans, and be able to make a diagnosis and start treatment as soon as possible. We know the earlier patients start on treatment, the better controlled their rheumatoid arthritis will be controlled.’
As for Sarah, she still has flare-ups, but says: ‘They tend to be short-lived. I dread to think how I’d be though if I hadn’t had the right diagnosis and my doctors had just relied on the blood tests.’