Amazing journey from easing symptoms to potential cures

11 minute read

Rheumatology has come a very long way in just a few decades, and the best may be yet to come

Rheumatology has come a very long way in just a few decades, and the best may be yet to come…

I have been privileged over my working life in rheumatology to see massive changes in our understanding of the immune system and disease processes, treatment options and the way they interact. It has been very rewarding to see the specialty grow with the development of a highly talented and skilled workforce in Australia.

When I did undergraduate medicine at Monash University, it was approximately a decade after McFarlane Burnett had done his ground-breaking work at the Walter and Eliza Hall Institute. He had discovered how the body’s immune system recognised “oneself” and, in the majority of cases, prevented the body from developing autoimmune diseases. This accounts for why these diseases are relatively uncommon. 

Some 10 years later, as a medical student, I learned there were both “smart” parts of the immune system consisting of both T and B lymphocytes as well as “dumb” parts to the immune system, the latter consisting of neutrophils, monocytes and other white cells. How these all functioned together was a complete mystery to me.

There were at this time, as I recall, less than 10 physicians in Victoria functioning as rheumatologists and as a consequence, very little training was available in Melbourne. My parent hospital (the Alfred Hospital) was not one of these and had no rheumatology unit.

I was, however, fortunate enough to transfer to the Austin Hospital for the latter part of my basic physician training. It was a hospital where a fledgeling rheumatology unit had just been established four years earlier. 

There was a weekly outpatient session followed by a brief inpatient ward round. With the relative absence of any treatments which might alter the course of disease for rheumatoid arthritis, it was important to have the support of dedicated therapists, including occupational therapy, physiotherapy, orthotics and access to a high-quality group of orthopaedic and plastic surgeons.

Standard patient management for such a patient would include frequent visits to a dedicated occupational therapist to provide hot wax baths for patients’ hands in order to encourage mobility and the making of both night-time and day hand splints for patients to wear.

A physiotherapist was similarly important, primarily directed towards stretching to trying to ensure that muscle contractures did not develop. This was particularly the case in rheumatoid arthritis as the actual human tendency is to flex both arms and legs when the joints were inflamed. If they were not stretched, these changes became permanent. Orthotists were essential for maintaining mobility, the impact of rheumatoid arthritis on the feet and ankles often being profound. 

Finally, the rheumatology unit needed the cooperation of excellent orthopaedic and plastic surgeons to manage the relevant bony and soft-tissue derangement which occurred because of the inflammation. 

The development of dedicated rheumatic diseases units was thus delayed in Australia compared with some countries overseas, especially in Victoria, where the state-based branch of BMA (predecessor of the AMA in Australia) was strongly opposed to the recognition of rheumatology as a specialty. These units enabled patients to be admitted for periods of prolonged bed rest complementary to the above interventions.

 It had previously been established in Scotland in the 1960s that six weeks of bed rest was of benefit in maintaining mobility despite significant levels of inflammation.

To our current way of thinking, the treatment of rheumatoid and the other types of inflammatory arthritis was archaic. Primary treatment was high doses of aspirin (3600mg daily). This was variably effective, with many people having, at best, moderate improvement in their symptoms. Such high doses were not also without potential side-effects, including marked tinnitus (a guide to maximal tolerated doses) and bleeding from stomach ulcers. 

The synthetic anti-inflammatory drugs (NSAIDs) were being sequentially introduced around this time. The perception was that somebody had not adequately trialled NSAID therapy unless they had either failed to respond, or had developed side-effects from, sequentially three different NSAIDs. At this time, one looked to see if there was evidence of joint damage on annual hand and foot X-rays and if this could be identified in the form of bony erosions, then it was appropriate to think about using a disease modifying anti-rheumatic drug (DMARD). 

These were described as disease-modifying agents since, at best, we were aiming to achieve amelioration of symptoms with the hope of slowing disease progress. The agents available to us at the time were intramuscular gold injections, penicillamine, hydroxychloroquine and rarely, sulphasalazine or azathioprine. Inherent in these observations, disease progress was common, both in the joints (with many people progressing to joint replacements) together with the development of other non-joint features such as rheumatoid nodules, Sjogren’s syndrome or vasculitis.

In 1976, rheumatology was recognised by the Royal Australasian College of Physicians (RACP) as a subspecialty of internal medicine and from then on, to become a rheumatologist, one had to undertake a formal three-year training program in rheumatology. Until that time, it was possible to become a general physician (MRACP) and with one year’s training (usually in an overseas unit), one could set about being a rheumatologist. 

The problem was that there was a relative absence of training posts in Australia. Thus, many young physicians sent overseas to units in England, Scotland, Canada and the US where rheumatology units were already well established. 

At a review of rheumatologist numbers early in the 2000s, 20 of the 44 practising rheumatologists in Victoria were training overseas in the late 1970s and early 1980s. I was fortunate enough to go to Ontario in Canada, first to McMaster University and then to University of Toronto. The rheumatic diseases unit at the University of Toronto was, at that time, world-renowned for its research into fibromyalgia and systemic lupus erythematosus (SLE) and had an excellent understanding as to the nature of autoimmunity and its translation into the various clinical disease processes we recognise as the autoimmune connective tissue diseases. 

Both the McMaster and Toronto units had a strong commitment to teaching, something I have carried with me, including when I returned to Australia. Treatment of active rheumatoid arthritis was “progressive”, since it consisted of only two weeks of bed rest with multiple injections of steroids (cortisone) into particularly the large joints. 

The Toronto unit had a large patient population with SLE together with a number of the other autoimmune conditions. My learning about these and other conditions such as psoriatic arthritis and ankylosing spondylitis was facilitated by the outstanding teaching in both institutions during daily inpatient ward rounds followed by a formal teaching session.

A number of my teachers have become internationally recognised for the quality of their research:  Dr Murray Urowitz for SLE, Dr Edward Keystone for his understanding of the management of early rheumatoid arthritis, Dr Dafna Gladman for both SLE and psoriatic arthritis and Dr Hugh Smythe for his ground-breaking understanding of the nature of fibromyalgia. 

Gout was always gout, and that didn’t change. In subsequent years, when I returned to Australia, I brought back this strong commitment to active education for my rheumatology trainees as well as a profound understanding of the above conditions. 

Following these three years of clinical rheumatology, I was fortunate enough to obtain a fellowship at the Kennedy Institute doing laboratory work under the supervision of Professor Sir Ravinder “Tiny” Maini and Dr Norman Staines. Using recently developed techniques, we isolated monoclonal antibodies of the type seen within SLE and undertook analysis of their significance. It was a further 10 years before Professor Maini undertook his ground-breaking work demonstrating that monoclonal antibodies developed using the same technology (e.g. anti-TNF antibodies) could be of value in the treatment of rheumatoid and other forms of arthritis.

In 1982, I returned to the Austin Hospital in Melbourne and helped develop the rheumatology unit. I saw the advantages of specialised clinics, both for the patients and rheumatology trainees, resulting in the establishment of both the first autoimmune diseases clinic and subsequently SLE clinic in Australia. 

In the mid-1990s, the then federally-funded Heidelberg Repatriation Hospital was amalgamated into the Victorian public hospital system with the establishment of the Austin and Repatriation Medical Centre. The Repatriation Hospital had one of the two rheumatology advanced training posts in Melbourne, the other being at the Royal Melbourne Hospital. Our trainee was responsible for both Rheumatology and Rehabilitation something which highlighted the hybrid origin of rheumatology in Australia. 

A number of the UK units, where several of my colleagues had trained, had their origins in the post-World War II rehabilitation units. They brought a much more physical medicine approach towards disease management which, together with the subsequently developed drug regimens, has been for the better treatment of people with arthritis.

It has now been approximately 20 years since monoclonal anti-TNF antibodies were introduced in Australia into the treatment for inflammatory arthritis and related conditions. For rheumatoid arthritis, the number of anti-TNF antibodies progressively increased to five. Three other biologic agents with different modes of action were also introduced and we are still trying to sort out whether there are advantages in using one agent over another ie the development of personalised medical treatment. 

It didn’t take long to establish that the anti-TNF antibodies also significantly help pain and mobility in patients with ankylosing spondylitis and related conditions such as psoriatic arthritis. Other injectable agents have subsequently been introduced into the PBS for the treatment of ankylosing spondylitis, psoriatic arthritis and most recently, giant cell arteritis. The variable ways in which people respond to these injections has given us great insight into possible pathogenic mechanisms of the underlying disease process. Two years ago, a JAK inhibitor (tablet) with similar efficacy of the above injections was also introduced onto the PBS. This was followed fairly quickly by a second agent and there are a number within the pipeline which will hopefully become available to us in the not too distant future.

Our institution has undergone subsequent name changes and it is now known as Austin Health. In the rheumatology unit, we now have people with expertise above and beyond that of general rheumatology in a spectrum of conditions including ankylosing spondylitis, systemic lupus, the use of ultrasound in musculoskeletal disease, rheumatoid arthritis, polymyalgia rheumatica and vasculitis. The spectrum of what we see in rheumatology continues to change. We have now developed expertise in the rheumatic side-effects of treatments used in the management of metastatic malignant disease, so-called immune related adverse events (irAEs). We are hoping a better understanding of these will give us insight into the origin and development of the equivalent conventional disease processes.

In writing this, it reinforces what an amazing and fulfilling journey this has been for me over the last 40-odd years. What seemed like a very ordinary beginning for a subspecialty where, at most, we were able to help people’s symptoms, we are now in a position where many people can potentially be returned to (drug-assisted) normal day-to-day activities and can hope that we will be able to “cure”, at least some of, these diseases in the foreseeable future. 

The amazing progress in development of drug treatments, the resultant increased understanding of the immune system and its mal-adaption leading to the development of autoimmune conditions and our understanding that we need to treat these diseases as early as possible to prevent damage, have all contributed to the progress of rheumatology as a respected and exciting medical specialty.  

In our rheumatology unit, we endeavour to utilise both drug treatment, combined with physical measures e.g. ultrasound and other imaging, for the betterment of our patients. We recognise the difficulties our patients have with chronic illness and pain and the importance of working together with our colleagues in many other specialties. 

We have established an excellent training program for people wanting to train as rheumatologists, no doubt influenced by my time in Canada. We have established an active research program, particularly in ankylosing spondylitis, systemic lupus erythematosus, polymyalgia rheumatica and irAEs. 

As I stepped down from the role of director of the rheumatology unit, I reflect that rheumatology still gives me what I liked about it in the first place: ongoing contact with people, being able to help them in the broader context of their individual lives, together with the intellectual stimulation of endeavouring to fully understand the rheumatic diseases.

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