Adult Onset Still’s Disease
By Dr Joel David FRCP, Rheumatologist, Nuffield Orthopaedic Centre, Oxford
Taken from: NRAS magazine, Winter 2011
Case History
Ruth was a 24-year-old post graduate student who had come from the USA to Oxford to do research. She had been fit and well with no serious childhood illnesses and no family history of any significant diseases. She had participated in sport and enjoyed dance. Ruth woke up one morning with a high temperature, a sore throat and muscle pains. Both she and her GP, whom she consulted, considered that she had a bout of flu. She took Paracetamol and drank plenty of fluids. By the mid afternoon her temperature had resolved and she felt somewhat better. This pattern of high fever and pains however repeated and for the next 10 days Ruth was unable to work. The fever seemed to be worse in the afternoon or evening. Her muscles continued to feel painful and were worse with the fever and her joints became uncomfortable particularly her wrists and knees. She also noted a pale pink rash which seemed much worse when she had her fever. Her GP found that she had numerous swollen lymph glands, particularly in her neck and under her arms. Ruth lost her appetite and lost weight. By day 10 of her illness she was admitted to hospital with a “fever of unknown origin”. In hospital it was found that she had swollen joints, a high swinging fever and blood tests that were consistent with severe inflammation. The Rheumatology specialists were called and a diagnosis of Adult Onset Still’s Disease was made.
Adult Onset Still’s Disease (AOSD) is an auto-inflammatory disease. This means that the inflammation is generated by a disturbance in immune function. The immune system generates inflammation autonomously – without the usual stimulus to inflammation, such as infection or injury. The condition affects both the joints and internal organs. It is usually present before the age of 40 years. Women are slightly more commonly affected than men. There are no known risk factors and there is usually no family history. Occasionally a virus may precipitate or trigger the illness, however a sore throat is very much part of the illness and therefore there may be confusion with a viral precipitating cause.
Symptoms of Adult Onset Still’s Disease
The cardinal features of the condition are fever, joint pains and rash. It is not uncommon though for the arthritis to present later in the illness. The patient may simply be very unwell with very high levels of inflammation in their blood and no other cause found. It is for this reason that patients with AOSD often present to the infectious diseases department. The fever comes on quickly, usually once a day in the afternoon or evening and then spontaneously resolves – often going below normal. The temperature may be associated with flushing. The rash which often, but not always, accompanies the fever is a salmon pink, blotchy, non itchy rash. It can however mimic many other rashes and on occasion may be itchy and appear like raised lumps. It is often on the upper arms, abdomen and thighs. When the patient has a fever they feel very miserable, with a headache and have severe muscle pain and often a very sore throat. Serositis, which is inflammation of the lining of the lungs (pleura), lining of the heart (pericardium) and lining of the abdominal cavity (peritoneum) may occur. This would account for severe chest pain particularly when taking in a deep breath. The lymph nodes which are swollen and tender are often widespread. This may raise the possibility of a lymphoma (cancer of the lymph nodes). Biopsy of the lymph nodes shows only reactive changes and no malignancy. Other diagnoses which need to be excluded include rare infections and inflammatory bowel disease. If the joint symptoms present early then it is less likely there will be a diagnostic delay.
The blood tests are helpful in making the diagnosis
They confirm a high level of inflammation (ESR and CRP). The rheumatoid arthritis tests such as rheumatoid factor and anti-CCP antibody, as well as the other auto-antibodies are all negative. Very often the full blood count will show a high white count and platelet count but there will be anaemia (low haemoglobin). This is because the high level of inflammation suppresses the manufacture of red blood cells and the utilization of iron in the marrow. In contrast, the ferritin, which is the iron storage protein, will be very high and this is often used as a diagnostic test. X-rays of the joints in the early stage are very likely to show no abnormality although joint swelling can be seen on x-ray – ultrasound would be more useful as a test to visualise inflammation of the joints. A chest x-ray may show an enlarged heart due to inflammation of the heart lining and because there may be fluid around the heart and in the lung cavity. The spleen, which is essentially a big lymph node, can be enlarged.
Once the diagnosis has been made then treatment needs to be commenced in order to relieve symptoms and to suppress the inflammation. This is important in order that the patient feels better but also so that the joints are prevented from being damaged. It is very difficult in the early stages to predict the course of the illness. A third of patients will have a mono-phasic illness. This means that the illness lasts a few months and then fades away with treatment and does not recur. A third of individuals will have a relapsing course with intermittent flare ups over subsequent years. These flare ups are often less severe than the first episode. A further third of individuals, however, will have a disease course which lasts a long time. They will require major immuno-suppressant therapy for control. There may be some effect on major organs. The joints that are involved are similar to those of rheumatoid arthritis and once the fevers and rashes have settled it may be difficult to differentiate the rheumatoid “hand” from an AOSD disease “hand”. The wrists are predominately involved as well as the small joints. Occasionally early failure of a large joint such as the hip may occur. This may in part be due to the very high doses of steroids that were used to control the inflammation at the start of the illness.
There is much research that is underway to understand the mechanism behind the auto-inflammatory disease and what generates the inflammation. It is known that high levels of the inflammatory protein interleukin-6 and interleukin-1 are present. The biological agents such as the monoclonal antibodies Anakinra and Tocilizumab are consequently becoming increasingly used for the treatment of this condition.
The early treatment is aimed at controlling the symptoms of fever and arthritis with anti-inflammatory drugs such as ibuprofen, naproxen and even high dose aspirin. These may be prescribed before the definitive diagnosis has been made. Analgesics such as paracetamol, codeine and tramadol may also be helpful. Corticosteroids such as prednisolone are very often used to control inflammation, fever and improve the anaemia. The anaemia that occurs is not responsive to normal treatments such as iron. When steroids are used they will often be given with other drugs to prevent steroid side effects. These would include protection against stomach ulcers (omeprazole or lansoprazole) and bone protection to prevent osteoporosis – alendronate and calcium. The aim is to use as low a dose of steroid as possible to control the inflammation but in the early stages it is often high doses and often intravenously that are required.
The disease will also need steroid sparing therapy for control – methotrexate which is the most commonly used disease modifying drug in rheumatoid arthritis is also used in AOSD. Cyclosporine is also sometimes used to prevent and treat a rare complication of AOSD called macrophage activation syndrome (MAS). This rare complication is associated with a precipitous drop in blood count and can potentially be very serious. Biological therapies that are often used include the anti-TNF agents infliximab and adalimumab and also, tocilizumab and anakinra. Once disease control has been achieved the drugs will be reduced very cautiously. It is usually not possible to predict prognosis until at least 1 year after onset of disease.
Once disease is controlled then there is no reason why the individual should not be able to work and function extremely well in everyday life. The steroids may have caused some weight gain but this will reduce as the steroid dose is reduced.
As with all chronic illness and particularly this disease which has such an impact when it hits, frustration and low mood may occur and much understanding, support and encouragement will be needed for the individual suffering and their family. Low self esteem and self consciousness is not unusual when individuals have put on weight due to the steroids, missed work or education and felt excluded from life. It takes time to “recalibrate” and this is important to recognise. The transition from being a healthy individual to being one who needs to take tablets, attend hospital appointments and have life adjustments needs to be acknowledged.