What is RA?

Professor Gabriel Panayi (formerly NRAS Chief Medical Advisor, now NRAS Patron), Arthritis Research Council Professor of Rheumatology, Guy’s, King’s, St Thomas’ School of Medicine
Original article: 02/07/2003
Reviewed: 13/03/2009
Next review due: 13/03/2011

Introduction By Ailsa Bosworth, Chief Executive, NRAS

If you think you may have RA or have just been diagnosed with RA, you will be feeling emotional, anxious and potentially afraid of finding out just what the future may hold in store for you. All this is perfectly understandable and I felt those things and many more when I was diagnosed 26 years ago.

You therefore need to understand a few things before reading the following article:

• The prognosis for people diagnosed with RA today is dramatically better than when I was diagnosed
• With early, aggressive treatment, you can lead a more normal life than has ever been possible before
• There are now very effective new drugs available if you fail conventional treatment
• There are lots of further drugs in the pipeline and more research than ever before happening around the world
• You have NRAS to support you and put you in touch with a volunteer ‘buddy’ who also has RA and has been through all the things you may be feeling right now, yet remains positive about the future.
• Knowledge of your disease will help you to come to terms with it and to make the right decisions about your treatment
• You can download this article and take it with you to the hospital next time you go, should this be helpful, and raise any particular question directly with your own rheumatology team.

NRAS is here for you and you can ring us at any time.

What is RA?

By Former NRAS Chief Medical Advisor, Professor Gabriel Panayi, now NRAS Patron

Rheumatoid arthritis is a serious disease if diagnosed late and/or treated inadequately.

I shall discuss the disease under the following headings:

• What is it?
• How does it come about?
• How does it present?
• How is it treated?
• What is the long-term outcome from the disease?

What is it?

Rheumatoid Arthritis (RA) is a chronic, progressive and disabling auto-immune disease affecting 0.8% of the UK adult population. It is a painful condition, can cause severe disability (this varies between individuals and depends on how severe/aggressive the disease is) and ultimately affects a person’s ability to carry out everyday tasks. The disease can progress very rapidly (again the speed of progression varies widely between individuals), causing swelling and damaging cartilage and bone around the joints. Any joint may be affected but it is commonly the hands, feet and wrists. It is a systemic disease which means that it can affect the whole body and internal organs (although this is not the case for everyone with RA) such as the lungs, heart and eyes.

It affects approximately 3 times more women than men and onset is generally between 40 - 60 years of age although it can occur at any age. There are around 12,000 children under the age of 16 with the juvenile form of the disease. We do not know what causes it although various ideas are examined later in this article. Cigarette smoking is an important precipitating factor. Furthermore, smoking makes the outlook for the RA worse. So far, we cannot cure it, but we now understand much more about the inflammatory process and how to manage it. RA is a lot more common than leukaemia and multiple sclerosis. However, because RA and its effects are not well publicised, awareness of the severity of the condition tends to be restricted to those who are directly affected or their carers and relatives.

The good news is that the prognosis today, if diagnosed and treated early, is significantly better than it was 20-30 years ago and many people have a much better quality of life in spite of having RA.

RA is economically costly. In fact, the total UK costs, including indirect costs and work related disability, are estimated to be approximately £3.8 - £4.75 billion per year. We now know that uncontrolled RA increases mortality through an increased risk of cardiovascular disease such as heart attacks and strokes; again the need for early treatment is imperative.

How does it come about?

A very common question asked by someone who first develops rheumatoid arthritis is, “Why me?” Although the cause of RA is unknown, some possible culprits including infections, viruses, diet and possibly injury, have not received strong scientific backing. As mentioned above smoking is undoubtedly an important factor in causing RA. Although rheumatoid arthritis has a genetic component, the possibility of passing the disease on to a child is extremely small.

How does it present?

• Joint swelling
• Pain
• Morning joint stiffness
• Poor sleep
• Fatigue
• Loss of weight
• A feeling of having flu like symptoms

The diagnosis of early RA is very difficult. From your point of view you should bear the following in mind. Joint swelling should be present in at least two joints. Along with this joint swelling there is stiffness in the joints, particularly in the morning or after sitting for some time. Osteoarthritis, or wear and tear arthritis, can also present with joint swelling and morning stiffness in the joints. However, the morning stiffness in osteoarthritis usually does not last longer than 30 minutes whereas in rheumatoid arthritis it is considerably longer. Patients with rheumatoid arthritis can wake up in the middle of the night with joint pain and stiffness. This does not happen in osteoarthritis. Fatigue is particularly pronounced in patients with rheumatoid arthritis and there may be loss of weight due to poor appetite – these are not features of osteoarthritis. If someone has some or all of the above features then they should consult their general practitioner. A relatively easy and cheap blood test, the ESR, will discriminate between RA and OA since it is increased in RA but not OA.

How Does RA damage joints?

Despite current lack of knowledge regarding the trigger of rheumatoid arthritis, we know a lot about the mechanisms by which the inflammation in the joints leads to their destruction. The processes of inflammation and destruction are known by the technical term of ‘pathogenesis’. All medical treatments for rheumatoid arthritis are directed at suppressing one or other part of the joint damaging processes.

A normal joint is a complicated machine involved in movement. It has several parts as illustrated in the cartoon below:

 

Normal joints provide movement that is effortless, requires little energy and is painless. In order to achieve this, a joint has to be adequately lubricated, just like the moving parts of a car. A joint is formed where two bones have to move one on each other as, for example, in the knee. The ends of the bones are covered with cartilage which is smooth so that one surface can glide over the other. The bone ends covered with cartilage are within the joint capsule, a tough coat keeping everything together. The lining of the capsule is called the synovium. It produces the joint fluid and is a very effective lubricant.

The normal joint lining is very thin. It has very few blood vessels in it and there are no white blood cells in it. In the inflamed rheumatoid joint, the lining is very different. It is very thick and is crowded with white blood cells that have entered it via new blood vessels as you can see from the next diagram. The white blood cells produce a large number of chemical substances that cause pain, joint swelling, and joint damage. These same chemicals, when released into the bloodstream, cause fatigue and general feelings of being unwell.

As a result of the entry of the white blood cells into the joint lining, they are activated and secrete substances that cause inflammation so that the joint is: swollen, hot, tender to touch, painful, functions poorly and may become deformed over time. It is the goal of every rheumatologist to try to prevent joint damage and the earlier and more aggressively someone with RA is treated, the better the long term prognosis.

The processes set in train by the white blood cells are also responsible for the damage to the cartilage and bone of the joint as can be seen from the diagram below:

To summarise the consequences of joint inflammation in the rheumatoid joint, see diagram below:

• The capsule, the outermost layer of the joint, is normal in both rheumatoid arthritis and osteoarthritis;
• The lining layer in the rheumatoid arthritis joint is swollen to many times its normal size;
• There are increased amounts of joint fluid between the bone ends;
• The inflamed synovial membrane eats into the bone and the cartilage. The damage of the bone is seen in the x-ray as an erosion.

More than the joints can be affected in RA

Other parts of the body can include: (but these areas are not affected in everyone with RA)

• Eyes - dryness, inflammation
• Lungs - fluid, fibrosis, nodules (rare)
• Skin - nodules, ulcers
• Heart - fluid, nodules, ischaemic heart disease
• Blood - anaemia, low counts

Your blood vessels and RA

Rheumatoid arthritis is itself a risk factor for heart attacks and strokes. It is therefore important that you consult your general practitioner and your rheumatologist to prevent these complications from taking place. This is done by controlling the activity of RA, treating risk factors such as diabetes, high blood pressure and high cholesterol. If you are a smoker, you must make a very determined effort to STOP.

How is rheumatoid arthritis managed? And what is involved?

• Patient education and empowerment
• Practical self-management to help deal with symptoms
• Multi-professional team care
• Drugs to control inflammation and disease progression
• Surgery to deal with structural change
• Specialist support to help live with the disease and its consequences

To help Symptoms

• Education and support
• Non-drug treatment including topical treatments and pain relieving strategies (rest and relaxation)
• Physiotherapy
• Occupational Therapy, painkillers, non-steroidal anti-inflammatory drugs (NSAIDs)
• Joint injections
• Pain Management Clinics

To Reduce Damage

• Disease modifying therapy (DMARDs)
• Steroids
• Biologic Agents

Knowledge of the pathogenesis of rheumatoid arthritis has been gained by many years of patient scientific research and is highly important because only through this knowledge can effective drugs be developed that can suppress joint inflammation and damage. Drug treatment is indicated for rheumatoid arthritis to control inflammation and joint damage. Unfortunately, if this control is inadequate, joint damage can only be corrected by orthopaedic surgery. The challenge today is to control rheumatoid arthritis as effectively as possible from its early stages so as to prevent serious joint damage necessitating surgery. This has already been achieved with many rheumatology centres reporting that the number of patients going to orthopaedic surgery over the last 10 to 15 years has significantly declined.

Treatment makes an important difference to the symptoms of inflammation, damage to the joints, how people can cope with RA and lifespan.

The Consequences of RA to the individual

• Pain
• Stiffness and ‘gelling’ after inactivity
• Unpredictable ‘flares’ of inflammation
• Fatigue
• Psychological Effects:
  • Anxiety
  • Depression
• Disability:
  • Loss of work
  • Loss of independence

Goals of Therapy

• To relieve symptoms including fatigue, pain, swelling and stiffness
• Prevent joint destruction, loss of joint function, deformity and disability
• Preserve quality of life
• Achieve clinical remission

The Rheumatology Team

It cannot be emphasised enough that the treatment of rheumatoid arthritis is a team effort involving many people. The critical therapeutic triangle involves the patient, the consultant, and the nurse practitioner. However, other members of the rheumatology team include physiotherapists, occupational therapists, chiropodists, podiatrists, orthotists, pharmacists, GPs and primary care nurses and orthopaedic surgeons. Some people also benefit from counselling services, although currently these professionals are not automatically part of every rheumatology team. Patients, ie YOU, are part of the management team. You must gain knowledge of the disease and of the drugs and procedures used for its treatment so as to be able to make rational decisions regarding treatment. By having this knowledge, you will also be an advocate for increased public and political awareness of the importance of this disease and the urgent need for adequate funding, both in terms of treatment and of the money needed for adequate research.

Effective Treatment needs to start early

We know that effective and early treatment of rheumatoid arthritis makes a very big impact on the subsequent course of the disease by improving quality of life and reducing joint damage. However, treatment should begin within 6 months of the onset of the disease or preferably even earlier, and it must be effective. We know that drugs and biologic treatments slow or even halt joint damage and improve the quality of life. Interestingly, methotrexate reduces the increased mortality of RA. This may also be true of anti-TNF alpha therapies. You will find further details of the treatments used in rheumatoid arthritis in other parts of the NRAS website. However I will cover the basics.

The drug management of rheumatoid arthritis is an established mode of treatment. This is achieved through the use of disease modifying drugs (DMARDs). Different strategies can be used:

• DMARDs may be used alone. Single DMARDs that are available include methotrexate, probably the commonest used, sulfasalazine and hydoxychloroquine, the anti-malarial. Leflunomide is a relatively recently introduced DMARD that inhibits the activity of one of the white blood cells called lymphocytes.
• DMARDs are now increasingly used in combination therapies which are more effective than the use of single drugs, without increasing toxicity. One of the commonest used combination therapies is methotrexate combined with sulfasalazine and hydoxychloroquine.
• It is likely that in the future, drugs taken by mouth will replace the present generation of biologics (requiring injection or intra-venous infusion). In this way, we will considerably reduce the cost of treatment and simplify the drug management of RA.

Biologics are presently used for the treatment of patients with rheumatoid arthritis who have failed treatment with DMARDs. Biologics in use at present inhibit the inflammatory mediator known as tumour necrosis factor alpha (TNFα). There are three anti-TNFα biologic drugs currently available. Infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira). Infliximab is given by intravenous infusion whereas Humira and Enbrel are injected at home by the patient after proper support and training. The anti-interleukin 1 inhibitor, Kineret, has a product licence in the United Kingdom but has not been approved by NICE (National Institute for Health and Clinical Excellence) for the treatment of RA. Consequently its use is limited. It is probably not as effective as the anti-TNF biologics. More recently Mabthera, which kills a specialised group of lymphocytes called B-cells, has been approved by NICE. It is used in patients who have failed anti-TNF therapy. Mabthera (rituximab) is given as an initial treatment of two infusions 14 days apart. Those patients who experience improvement lasting up to six months can then have repeat infusions.

As you will realise, research is constantly producing new treatments for RA. Our role is to keep you informed of all new developments and ongoing research. We will also let you know of any assessments of the effectiveness and availability of new treatments.

RA - Barriers to more effective treatment

Unfortunately there are barriers to effective treatment. Undoubtedly one deficiency is the lack of rheumatologists, nurse practitioners and allied health professionals. Another is the lack of adequate funding due to the failure of full implementation of NICE Guidelines on ‘biologic therapies’. In this regard, NRAS has been a prime mover in obtaining adequate funding. It is to be hoped that the present financial problems of the NHS do not put back the gains that have been made in the management of rheumatoid arthritis.

RA - The Challenge to Society - Summary

In summary therefore, rheumatoid arthritis is a major challenge to the individual patient and to society. It can be treated effectively if it is diagnosed early. This means better general practitioner education and early effective treatment. From the patient perspective, early rheumatoid arthritis may not easily be distinguished from other forms of less severe arthritis. The golden rules are:

IF YOU HAVE SWELLING OF MORE THAN TWO JOINTS AND WITH STIFFNESS IN THE JOINTS IN THE MORNINGS OF MORE THAN HALF AN HOUR THEN GO AND SEE YOUR GENERAL PRACTITIONER.

STOP SMOKING - IT WILL IMPROVE YOUR RA AND REDUCE RISK OF HEART ATTACKS AND STROKES.

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