Arlet and Ficat have given their names to a classification system of femoral head necrosis known to surgeons everywhere. We spoke to Jacques Arlet, a clinician, researcher, teacher, and a great personality, who told us, in simple words, how he was drawn towards rheumatology at a time when this discipline was in its infancy. He also showed us how scientific breakthrough does not necessarily result from huge and costly research projects.

 

nom M.O. You have been Professor of Rheumatology at Toulouse Medical School, for over thirty years. What was rheumatology like when you were training as a specialist?

J.A. Allow me to correct your statement concerning my academic seniority: It is true that I have been teaching rheumatology for over thirty years; however, I was made a Professor only twenty years ago. Initially, from 1959, I was just a hospital doctor. I have, actually, been in rheumatology for almost fifty years, because I started setting up a Rheumatology Unit when I was still in training on a Medical Unit, at Purpan Teaching Hospital, back in 1947. However, at that time, rheumatology did not exist as a specialty in its own right. There were some doctors in Paris - De Seze, Coste, and Lièvre, for instance, - who had started doing rheumatology work as part of their hospital activities; also, there was an excellent centre at Aix-les-Bains. So, when I decided to specialize in rheumatology, I went to Paris and to Aix-les-Bains. I spent a few months on this apprenticeship, which was absolutely vital.

M.O. Why did you choose this specialty?

J.A. Prof. Riser, who taught me, wanted me to go into Psychiatry; however, that idea was not very long-lived: I was not really cut out for that. I wanted to do something medical, and some of the specialties were getting a bit crowded: chest medicine had been excessively popular for a long time; and cardiology was being taken over by several of my friends and by some of the younger lecturers. However, there was no such specialty as “musculoskeletal disorders” or “rheumatology;” so I decided that I would go into that field. In actual fact, I was being a bit ambitious, and a bit foolhardy, because I wanted to tackle the locomotor apparatus both from the medical and from the surgical end of the business. However, I was not all that young any more, since I had started specialty training rather late in the day; so being both a physician and a surgeon was out. I was married by then, with a family, so I had to be able to make a living as soon as possible. Which is why surgery went by the board.

M.O. What sort of rheumatic disorders were being treated back in the ‘50s?

J.A. The field was vast - which is why it was so interesting. It was totally absorbing, because, when all is said and done, one was dealing with the entire locomotor apparatus - all the bones and joints, for example; but also rheumatoid arthritis, and the tendinitides, sciatica and myeloma. Some of these diseases were the Cinderellas of the other fields, with nobody really interested in them. I remember Prof. Riser (whom, goodness knows, I admired greatly) not being able to abide sciatica; he simply was not interested in that condition. So the rheumatologists took over these diseases - Forestier did, and De Seze; and I myself started looking into sciatica, which I found hugely interesting, because its treatment is mainly medical, with physical therapy. Of course, I also dealt with RA, which no one was interested in at the time, and which was often not even diagnosed. Even the best internists very, very often failed to diagnose the condition: they would think of rheumatic fever, of joint infections, of tuberculosis; RA rarely came to their minds. The situation was so bad that I went to the charity hospitals for the incurable to find patients with severely incapacitating RA; I brought these cases back to the unit run by my own teacher, Prof. Roques. By then, we had changed hospitals; we had left the Hôtel-Dieu in Paris to go to the Purpan in Toulouse, where we had plenty of space that needed filling. Each medical unit had three floors of wards, without any labs, without any examination rooms, without anywhere for the doctors to go - a desert. Old Prof. Roques then said to me, “Listen, you are keen on rheumatology; so am I. You could try and put some of your rheumatic patients into the upstairs wards; that way, we could fill the space.” So that was that. And that is how I was given a completely free hand, while I was still a junior doctor, to set up a small Rheumatology unit to look after RA, and sciatica, and everything to do with inflammatory and degenerative joint disorders.

M.O. Treatment-wise - what did you have in those days?

J.A. By way of anti-inflammatories, we didn’t have much, apart from aspirin; however, in 1949, cortisone was introduced, and that revolutionized the treatment of our patients. Incidentally, I was involved in the first trial of cortisone in RA, which I was asked to carry out at Toulouse, because we had received a small amount of cortisone, which had to be used following very strict rules and with close monitoring of the patients. What struck me at the time was that some patients obtained lasting relief from twenty days’ treatment. This was far more interesting to me than seeing them relapse, because it was common knowledge that RA patients would relapse. So there were some who would be permanently cured: this fact stuck in my mind, and that was how, eventually, we came to use moderately high initial doses, which induce a remission that will be of lasting effect in a great many RA patients. Then butazolidine came in shortly afterwards, and proved very efficacious. Let’s face it, when it comes to anti-inflammatories, the most effective ones are cortisone and butazolidine; I don’t think there is anything better. By way of second-line drugs, we had, of course, the gold salts. The Americans were not using them; now they are. Gold salts induce a lasting remission; they are a great invention. After the War, Forestier first used them in a carefully controlled and systematic way in RA patients. So he did the groundwork, which was immediately seized upon by the Brits and the Germans, though not by the Americans, although Forestier had gone over there in ‘37-’38, to present his results.

M.O. Do you think that fundamental progress has been made, over the past ten years, in the treatment of rheumatic disorders?

J.A. Yes, absolutely: there has been progress since I first went into rheumatology. The three greatest advances, to my way of thinking, are, firstly, the prevention of rheumatic fever, which was still around in the ‘50s, and which has completely disappeared. Secondly, the control of hyperuricaemia, which allows us to treat gout efficaciously. In 1950, my colleague Charles Laporte and I saw 100 cases of gout; during the War, it had disappeared, perhaps because of the diet forced upon us by the Germans; it had then come back massively after the War. The third major advance that I can see is implants, especially hip replacements.

On the pharmacology side, there have been no miracle drugs to match the efficacy of cortisone; however, we are now able to control steroid treatment better than in the past: we know the dangers of cortisone and its limitations; and we have also acquired greater control of the cytotoxic drugs used in the treatment of inflammatory rheumatism. And there has been undoubted progress in the treatment of bone diseases, with the advent of calcitonin and the bisphosphonates.

M.O. You seem to have worked very closely and very well with Paul Ficat. How did you meet him?

J.A. I met him when I was in a bit of a vacuum, having been somewhat abandoned by the professor of Medicine who had followed my first boss, and who did not want me there any more. So Ducuing came to my rescue. He allowed me to set up a little laboratory for synovial fluid research - that was a subject no one in France had looked into previously; I myself had come across it in the States, in 1952. So, on my return, I set up a little lab, with a small grant from the French National Institute of Health (the forerunner of the French Medical Research Council INSERM). I had got myself a microscope, and was working with a Spaniard, who was a very skilled microscopist. Paul Ficat, who had trained under Ducuing, came to the lab; we started working and doing a bit of research together. One day, Ducuing said to us, “You know, I am sure that disorders of the bone circulation are important. You ought to look into that subject.” At Toulouse, quite a few techniques for the study of bone blood supply had been introduced by then - perosseous venography, for instance, and arteriography. I went to England for a few months, to spend some time in Professor Trueta’s department at Oxford; he was a pioneer of this new venture into the study of the bone blood supply; it was he who had shown the importance of this supply in any bone disorders and diseases of the locomotor apparatus. I learned to do intraosseous arteriography; I learned the anatomy and physiology of the blood vessels in the bones; and when I returned to France, I started researching this subject together with Paul Ficat, who was then Rieunau’s second in command. When Ficat had got his own Department and established his own school, he was kind enough to get me some space for my lab on the floor below his, on a Rheumatology unit. So we were working very closely together. He also had a Rehabilitation Unit in those days, on the ground floor of the Hôtel-Dieu. This was marvellous: every aspect was taken care of, and the whole thing got called a Department of Bone and Joint Disease. I must say that I was very keen on surgery - so much so that I would often say to Ficat, “This patient needs an operation.” And Ficat would say, “No, he doesn’t.” So I was pushing, and Ficat was holding back; that may sound odd, but that’s how it was.

M.O. In the ‘60s, was osteonecrosis of the femoral head often diagnosed in patients presenting with hip pain?

J.A. No, certainly not. ON was only just beginning to be known; what doctors were mainly looking for was non-specific infections, tuberculosis, or secondaries; OA was bottom of the list of possible diagnoses. Of course, in a hip clinic, OA would be the most frequently encountered condition. Just every now and again, doctors would see something that was a little out of the ordinary - and then they would think of ON.

M.O. What is the history of ON?

J.A. The pathology of the condition was first described by German authors, in particular by Koenig, at the beginning of the century; and one may even say that, right from the start, these authors thought that the condition was due to ischaemia and even to arterial occlusion - which, to this day, is considered the most plausible hypothesis. However, I think that the diagnosis was missed for a long time, and the patients were treated like the large population of OA and chronic hip disease sufferers. It was not until the ‘60s that, in France, femoral head ON was re-created: it came into its own again, with excellent and very accurate clinical descriptions, thanks mainly to doctors in Paris. Virtually all the features of the condition were described, including the preradiological stage, although that was dealt with a bit sketchily, perhaps.

M.O. How did you become interested in femoral head ON?

J.A. Ficat had the idea of using a cannulated drill instead of a solid one, so when he drilled he obtained a core sample of bone. That’s how it all came about. What he did was, in fact, a mixture of applied research into the therapy of avascular necrosis, because core decompression had already been described in Lyon, especially by Duvernet, and of basic histopathological research. This is where my little lab came in handy: as a facility, it was nothing to write home about; however, it allowed one to study synovial and decalcified bone samples, and we were soon able to describe the patterns of ON at all the different stages, and, thus, to revive and revitalize the whole question. Our chief contribution was the histopathological investigation, which showed that ON starts before there are any radiological signs; this idea is now universally accepted, but for a long time it was hotly contested by other researchers.

M.O. Your system comprises four stages, because it includes this preradiological phase. Has this stage always formed part of your system, or was it a later addition?

J.A. It certainly wasn’t added later on - to us, Stage I has always been an essential part of the history of the disorder. Everything else is quite straightforward, because once you see X-ray signs, the diagnosis can be readily made; and once the femoral head has collapsed, that’s it - there is no doubt about the diagnosis, and, unfortunately, no doubt about the prognosis, either. Stage I, though, is purely histological, and that is the essential point. This is the idea that we have contributed to osteonecrosis research, and it was on this idea that we were severely challenged in the early days. My friend Mazabraud, who is a bone histopathologist, came to spend a whole day with us at Toulouse, and viewed our slides for hours on end. Finally, he said, “Got to admit it - you’re right.” Many, though, felt that what we had shown was a different disorder. Now, since the advent of MRI, there is no longer any argument. The chief concern to us was that, at that early stage, the condition was, perhaps, still curable.

M.O. What your opponents were saying was that what you were calling Stage I in your core biopsies had, in fact, come from cases of reflex sympathetic dystrophy. MRI has shown that this condition does occur, but is very much less frequent than ON.

J.A. Yes, reflex sympathetic dystrophy is an interesting subject, and a very important one, too, because it has been put back on the agenda by Austrian surgeons of the Hofmann group, and the Austrian pathologist Plenk, who say that reflex sympathetic dystrophy is Stage I of osteonecrosis - not in all cases, but certainly in some. And then they say, “Why don’t you decompress them, because decompression provides immediate pain relief, and the patients are cured much faster.” As far as their first contention is concerned, I would say, “No, I do not think that reflex sympathetic dystrophy is the first stage of osteonecrosis,” - and I have spent hours arguing this point with Hofmann and Plenk. Also, the histopathological pattern of RSD is totally different from that of Stage I ON as we have described it: ON is usually marked by diffuse bone marrow lesions, rather than by the oedema, fibrosis, and osteoidosis that are characteristic of RSD. This point has not been properly understood even by my French friends. I can state categorically that these two conditions are different, even though, in some cases, they may occur in the same context, and their causes may, at times, be very similar.

M.O. Since we are on the subject of histology, is there a correlation between the histological staging of ON and the radiological staging?

J.A. That’s a more difficult question, and I’ll tell you why. My immediate answer would be, “Yes, on the whole, the radiological stages and the histological stages are related - but not always.” As to the reason why they may not be related, I think that, firstly, we have to rely on core biopsies - in other words, the specimen comes from only part of the femoral head, and the drill site may not have been optimal for obtaining evidence. Secondly, it should be realized that radiography or the additional, more recent, technique of MRI do not enable us to make a histopathological diagnosis. It is wrong to say, on the strength of an X-ray or an MRI scan, that what we are seeing is the extent of the necrosis: these imaging techniques provide indirect evidence only; they most certainly do not give us the histology. So if one wants to determine the volume or the extent of the necrosis, imaging techniques offer only a very rough and ready guide. The zone above that much-cited borderline between the dead and the living bone is not always gone for good. I do not think that one can say that everything above that line has become a necrotic sequestrum. This is a difficult problem that has not, as yet, been properly resolved.

M.O. There appears to be agreement now that very small necrotic areas will not go on to fracture, while the very large ones, the ones that are greater than fifty per cent, will almost invariably fracture. How do you see this?

J.A. I agree with the volume concept, which partly explains the further course of the condition; however, we should not get too carried away. Core decompression works, but this may, to some extent, be due to the fact that a small necrotic focus, if left untreated, will resolve spontaneously. This is what happens with cysts away from the joint surface: the cysts will either remain stationary, or they may even heal. However, if there are major lesions, one may wonder whether they will heal. Unfortunately, I never did routine measurements of the volume of necrotic lesions, so I have no detailed evidence; however, I do remember lesions that looked very large on X-rays clearing up after decompression.

M.O. Nowadays, core decompression is combined with new techniques such as bone autografts, vascularized autografts, cement injection, electrical stimulation of new bone formation, autologous bone marrow injections, even injections of osteoinductive proteins. What are your views on these treatment principles?

J.A. Of course, I think that there is much in all this that is of importance; but it all depends on the stage of the lesion. In Stage I lesions, I do not think that one could improve on the results of core decompression. Steinberg has done the largest numbers of decompression with grafting, and has produced very interesting and important statistics. These statistics show that, in Stage I, the results of decompression plus grafting are not all that different from just decompression. As regards the injection of osteoconductive substances, I find this approach very interesting, and I am looking forward to seeing the results. However, I am not sure that vascularized grafts have all that much to offer in Stage I lesions; whereas in Stage II lesions, where the X-rays show extensive necrosis, I think that this technique should be pursued further, providing that one does not perforate the bone shell that is still in good condition. Also, this technique is difficult, and should therefore be practised only by those who have the necessary skill and expertise.

M.O. What is ARCO?

J.A. ARCO stands for the Association de Recherche sur la Circulation Osseuse. There was a long debate at the founder meeting in London, in 1989; the acronym was, eventually, adopted because the words that make up the French name can also be used in English - Association Research Circulation Osseous. Everybody was in favour - and that meant the French, British, Japanese, and American participants. The organization is a research foundation, which encompasses clinical as well as basic research. The Association comprises clinicians, orthopaedic surgeons, who do not do a lot of research themselves; and pure researchers, who do research into basic physiology, nuclear medicine, etc.; there are even some haematologists. The whole thing is very big; and it’s not all about osteonecrosis. Rather, the Association deals with all aspects of bone disease and all aspects of intraosseous circulation, because we could say that in any bone disease there will be involvement of the blood supply. There are about 200 of us in the Association. I had the honour of being its President for five years. My successor was John Paul Jones, a Californian orthopaedic surgeon. The current President is a Dutch orthopaedic surgeon called Gardeniers. The organization is very cosmopolitan: there are quite a few American members, and many from the Far East - from Japan, Korea, even some from China, and a few from Singapore.

M.O. Where will the next ARCO congress be held?

J.A. The venue for the April ‘99 ARCO congress will be Sydney, Australia; Prof. Cheras and Prof. Ghosh are organizing the convention. Then, there should be a conference in Toulouse, around the year 2000. ARCO meets once a year, and is a very open forum: anyone interested is welcome. There are always participants there who are not members of the Association. ARCO also publishes a twice yearly newsletter, which contains interesting information on what is new, on research in progress; it also gives very helpful summaries of papers published anywhere in the world, in the field of bone circulation. Osteonecrosis is a subject of particular importance; however, other bone disorders are covered as well. So, anyone who has the complete set of ARCO newsletters (which provides an indexed collection of information) will find references to hundreds of articles on bone blood supply. Since ARCO is a very modern organization, all you need to do if you want to obtain further information, or if you would like to join, is go to the Internet (http://www-sv.cict.fr/arco).

M.O. You have written a life of Jacques Forestier. Is his work receiving the recognition it deserves?

J.A. I think so, yes - you only have to look at what happened at an international congress of rheumatology in San Francisco, back in the ‘70s: the congress started with a glowing tribute to Jacques Forestier, with a film shown on a huge screen, etc. He not only worked with his father to set up the European League Against Rheumatism, but I think that that we owe him major contributions to rheumatology as such. He helped to bring about the spectacular advances in the use of gold salts,; he improved the diagnosis of rheumatic disorders; and he described new disease entities such as ankylosing hyperostosis (also known as DISH) or polymyalgia rheumatica. He was a lovely person, and a superb clinician. And I think that rheumatologists world-wide appreciate his qualities and his work.

M.O. You are a professor from Toulouse, yet you speak without a trace of a southern French accent. How come?

J.A. That’s simple - I do not come from Toulouse. I was not born in the south of France, even though both my parents were southerners, from the Dordogne; I grew up in eastern France and in Paris. There was no reason why I should acquire a southern accent, since my parents spoke standard French. And even when I went to Toulouse, I did not pick up the local speech pattern, although I threw myself wholeheartedly into the lifestyle of the place.

M.O. You are now retired, but you are still organizing international conferences on bone circulation and osteonecrosis. Do you have any time for leisure activities?

J.A. I am working a lot less now, having reduced my hospital activities to zero, and also doing less conference organizing. In fact, I have not been doing any for the last couple of years. Before that, even though I had given up my hospital work, I was busy with the ARCO newsletter, and I did lots of reviews and papers. But that’s all over now. And anyway, once I had left the hospital, I had plenty of spare time.

M.O. So what do you do in your spare time?

J.A. Well, I read, I go for walks, I do a bit of hiking in the mountains; and then, a few years ago, I took up writing and painting. I had been painting for a long time, it was something I did mainly during the three weeks’ annual leave that I used to take. Now, since I am doing less walking, my favourite pastimes are reading and writing (but not about medicine), and also painting.

M.O. I understand that you lecture on Georges Simenon. What attracted you to that writer?

J.A. I am not the only one to be fond of Simenon; he has had other fans before me: André Gide thought of him as one of the greatest novelists of our time. I love Simenon because I think that he is not just a writer of whodunnits, but a subtle psychologist, with a profound knowledge of the human psyche; he is one of those remarkable authors that give one a feeling that they have seen everything, and experienced everything; one wonders whether they have a very special brain. The other thing is that many of Simenon’s characters are doctors. Simenon liked doctors, there were lots of medics in his circle of friends. I did a little exercise once, just for fun, analyzing the medical characters in about a hundred Simenon texts. In his books, he portrayed all sorts of doctors, from country GPs to forensic pathologists, big hospital consultants, etc. And all these characters are beautifully sketched.

M.O. What non-medical works have you published?

J.A. I have written stories, but they were never published; they were for family consumption only. My first published work was the life of Jacques Forestier. I found writing this biography fascinating, and decided there and then that I was going to write about subjects other than medicine - because in the Forestier biography, there are two medical chapters, but all the rest is just about his life: and goodness knows, his life was full of things that had nothing to do with medicine. I then wrote another biography, of a very unusual priest, Father Casy Rivières. I had known him and met him myself, and it had been agreed that I would write a little book about him, in the form of a dialogue. However, he died; so I wrote his biography, because I had been given all the letters he had received from famous writers. The book did quite well. I then thought I would go on writing biographies, but actually got stuck into the history of daily life in Toulouse in the 19th century. I wrote a first book on life in Toulouse in the second quarter of the last century; and another one, on daily life in Toulouse during the 1852-1870 period; and now I am researching a third book, on life in turn-of-the-century and pre-WWI Toulouse. I am hoping to bring out this volume around the year 2000, if the good Lord lets me live that long.

M.O. Do you think that medical schools should be liberal in admitting students with arts rather than science subjects in their leaving certificates?

J.A. Yes - most definitely, yes. I myself took both science and arts subjects to university entrance level, although that was easier in my time than it is now. I was, therefore, quite good at maths, but, truth to speak, the level in my year was not that high! I subsequently did not use my mathematics in my work as a medic, and, frankly, I cannot see where it would have been useful. However, I did, occasionally, seek the help of statisticians. I think that medicine and biology are not exact sciences in quite the same way as mathematics: there is always an element of approximation that has to be borne in mind, just as in philosophy. So, we could say that scientific rigour = scientific honesty: the two amount to the same thing, don’t they? And this honesty can be acquired equally well if one is doing French, or Latin, or history, providing that one is studying these subjects thoroughly and that one has good teachers. And I think that acquiring this honesty helps to make one a good doctor.