338 Letters to the editor

1 Edlund E, Johnsson U, Lidgren L, et al. to be most unusual.' Cricothyroid arthritis in and blood of patients with B27 associated Palmoplantar pustulosis and sternocostoclavi- the course of familial Mediterranean fever has peripheral arthritis following trauma, in an cular arthro-osteitis. Ann Rheum Dis 1988; 47: 809-15. not been previously described. attempt to understand the pathogenetic mech- Ann Rheum Dis: first published as 10.1136/ard.49.5.338-c on 1 May 1990. Downloaded from 2 Fallet G H, Arroyo J, Vischer T L. Sternocosto- The presentation with migratory polyarti- anisms. We appreciate the comments of clavicular hyperostosis. Case report with a 31- cular arthritis, the involvement of the inter- Professor Panayi and thank him for drawing year followup. Arthritis Rheum 1983; 26: 784-90. phalangeal joints, and the long period before attention to this topic ofseronegative spondylo- 3 Sonozaki H, Mitsui H, Miyanaga Y, et al. the appearance of the classical manifestations arthropathy. Clinical features of 53 cases with pustulotic of familial Mediterranean fever are other arthro-osteitis. Ann Rheum Dis 1981; 40: unusual features in this case. IGNAZIO OLIVIERI* 547-53. GABRIELE GEMIGNANI 4 Gerster J C, Lagier R, Nicod L. Sternocosto- FAISAL A KHUFFASH GIAMPIERO PASERO clavicular hyperostosis (SCCH). Skeletal Radiol HASSAN A MAJEED Rheumatic Disease Unit 1985; 14: 53-60. Department ofPaediatrics Institute ofMedical Pathology I 5 Sartory D J, Schreiman J S, Kerr E, Resnik C S, Faulty ofMedicine Universiy of Pisa Resnick D. Sternocostoclavicular hyperostosis: Kutvait Universi Pisa, Italy a review and report of 11 cases. Radiology 1986; PO Box 24923 158: 125-8. 13110 Safat, Kuwait *Correspondence to: Dr Ignazio Olivieri, Istituto di 6 Chamot A M, Benhamou C L, Kahn M F, Patologia Medica 1, Servizio di Reumatologia, Via Roma 67, 56100 Pisa, Beranek L, Kaplan G, Prost A. Le syndrome I Heller H, Gafni J, Michaeli D, et al. The arthritis Italy. acne pustulose hyperostose osteite (SAPHO). offamilial Mediterranean fever (FMF). Arthritis Resultats d'une enquete nationale. 85 obser- Rheun 1966; 9: 1-17. 1 Panayi G S. Trauma and seronegative spondylo- vations. Rev Rhum Mal Osteoartic 1987; 54: 2 Majeed H A, Barakat M. Familial Mediterranean arthropathy. Ann Rheum Dis 1989; 48: 879. 187-96. fever (recurrent hereditary polyserositis) in 2 Olivieri I, Gemignani G, Christou C, Pasero G. 7 Karagevrekis Ch, Failet G H, Lagier R. Spinal children: analysis of 88 cases. Eur J Pediatr Trauma and seronegative spondyloarthropathy: changes in association with sternocostoclavicular 1989; 148: 636-41. report of two more cases of peripheral arthritis hyperostosis. JBR-BTR, in press. 3 Sneh E, Pras M, Michaeli D, Shahin N, Gafni J. precipitated by physical injury. Ann Rheum Dis 8 Lagier R, Arroyo J, Fallet G H. Sternocosto- Protracted arthritis in familial Mediterranean 1989; 48: 520-1. clavicular hyperostosis. Radiological and patho- fever. Rheumatology and Rehabilitation 1977; 3 Wisnieski J J. Trauma and Reiter's syndrome: logical study of a specimen with ununited 16: 102-6. development of 'reactive arthropathy' in two clavicular fracture. Pathol Res Pract 1986; 181: 4 Simon G, Marbach J J. Familial Mediterranean patients following musculoskeletal injury. Ann 596-603. fever with temporomandibular joint involve- Rhewn Dis 1984; 43: 829-32. ment. Pediatrics 1976; 57: 810-2. 4 Masson G, Thomas P, Bontoux D, Alcalay M. Influence of trauma on initiation of Reiter's Cricothyroid arthritis in a child with familial syndrome and ankylosing spondylitis. Ann Mediterranean fever Rheun Dis 1985; 44: 860-1. Trauma and seroneptive 5 Jacobs J C, Berdon W E, Johnston A D. HLA- B27-associated spondyloarthritis and entheso- Sir: We describe for the first time the occur- spondyloarthropathy pathy in childhood: clinical, pathologic, and rence of cricothyroid arthritis in a girl who radiographic observations in 58 patients. J first presented with migratory polyarticular Sir: We would like to offer what we believe to Pediatr 1982; 100: 521-8. developed the classical be a necessary reply to Professor Panayi's 6 Olivieri I, Gherardi S, Bini C, Trippi D, Ciompi arthritis but eventually M L, Pasero G. Trauma and seronegative features of familial Mediterranean fever. letter published in the Annals.' Professor spondyloarthropathy: rapid joint destruction in A 9 year old Palestinian Arab girl was Panayi considers that in the two B27 positive peripheral arthritis triggered by physical injury. admitted in January 1979 with fever and patients we described, who developed peri- Ann Rhewn Dis 1988; 47: 73-6. 7 Williams K A, Scott J T. Influence of trauma on migratory polyarticular arthritis of the large pheral arthritis immediately after trauma,2 the development of chronic inflammatory poly- joints. The heart was normal. The erythrocyte physical injury and the onset of peripheral arthritis. Ann Rheun Dis 1967; 26: 532-7. sedimentation rate was 110 mm/h and the arthritis were only coincidental. The first case 8 Wright V. Psoriatic arthritis. In: Scott J T, ed. 0 titre was 400 Todd units. A represents, in his opinion, a reactive arthritis Copeman's textbook of the rheumatic diseases. 6th antistreptolysin ed. Edinburgh, London, Melbourne, New diagnosis of acute rheumatic fever was made following gastroenteritis, and the second case, York: Churchill Livingstone, 1986: 775-86. and treatment was started with secondary arthritis of the knees begun by chance after prophylaxis. During the following six years the trauma. http://ard.bmj.com/ she had several episodes of arthritis, which If other articles on this subject' are not were interpreted as recurrence of acute rheu- taken into account this may seem to be the Chondroprotective drugs and osteoarthritis matic fever due to irregular prophylaxis, and most logical conclusion, partly because no occasional fever and abdominal pain. evidence of causality may be produced other Sir: I read with interest the leader article by In January 1985 the girl was admitted with than the immediate onset ofperipheral arthritis Doherty on 'Chondroprotection by non- fever and arthritis of both elbows and the right after trauma, and the lack of an infective steroidal anti-inflammatory drugs' published wrist. Next morning she developed arthritis of trigger. Wisnieski3 and Masson et alP have in the Annals.' the cricothyroid joint. The diagnosis was reported other cases of peripheral arthritis in Although I am in general agreement with on September 27, 2021 by guest. Protected copyright. verified by indirect laryngoscopy. She also B27 positive subjects immediately after physi- the views expressed by Dr Doherty, he raised developed arthritis ofthe interphalangeal joints cal injury. In some of these, like our patient some issues which I consider deserve further of both hands. She became better after five 12 there was also urethritis with negative comment. days of aspirin treatment. Two months later urethral smears and culture, in addition to In his article Dr Doherty questions the she had another similar episode of transient arthritis. Our patient also had a diarrhoea relevance of certain laboratory derived data arthritis of the cricothyroid and interphalan- with negative stool culture, which subsided in on non-steroidal anti-inflammatory drugs geal joints. During the following three years two days without any treatment. In 1982 (NSAIDs) to their clinical use in osteoarthritis. the girl had several episodes of fever and Jacobs et al reported that five of their 58 He considers the standard for assessing these abdominal pain, with the frequency progres- patients with juvenile onset B27 positive drugs is the long term symptomatic and sively increasing to one to two attacks a week. spondyloarthropathy had a trauma severe functional improvement in patients 'rather She also developed arthritis of the ankles enough for a doctor to be consulted before the than individual biochemical or structural associated with erysipelas-like erythema. onset of peripheral arthritis.' In 1988 we characteristics'. It should be noted, however, Family history disclosed that her mother, a reported the cases of two B27 positive subjects that most NSAIDs are also powerful analgesics maternal aunt, and two sisters had had similar who had never had pain to peripheral joints and may effectively relieve the symptoms of recurrent episodes. Prophylaxiswith colchicine before, but developed an erosive peripheral osteoarthritis without necessarily influencing was effective in decreasing the frequency of arthritis of the right hip shortly after a severe its progression. Pain relief and improvement febrile and painful episodes; during the past physical injury to the same joint.6 The rapid of joint mobility are thus inadequate criteria 12 months the girl has had only three mild evolution of the destructive process, which is for distinguishing between an NSAID acting abdominal attacks and one episode oftransient not usual in erosive arthritis of seronegative only as an analgesic and an NSAID which is arthritis of the left ankle. spondyloarthropathy, provides further evi- also positively influencing the underlying Thesynovialattackoffamilial Mediterranean dence in favour of the triggering role of osteoarthritic disease. More objective methods fever typically appears as acute monoarthritis trauma. of clinical assessment of patient response to affecting a large joint ofthe lower extremity. ' In conclusion, the articles published on the drug treatment are therefore required before Involvement of the small joints, including the subject suggest that as in psoriatic arthro- this matter can be resolved. Such methods are temporomandibular, sternoclavicular, and pathy,7 8 physical injury may, in B27 positive presently under investigation, and promising metatarsophalangeal joints, has been de- subjects, trigger the onset of a peripheral findings have been reported with biochemical scribed in a minority of patients with familial arthritis predominantly affecting the injured markers of cartilage breakdown in synovial Mediterranean fever,'4 whereas involvement joints. We hope that others will report similar fluid2 and serum,5 6 x ray microfocal of the interphalangeal joints has been reported cases and perform studies on the synovial fluid (Buckland-Wright et al, unpublished data) Letters to the editor 339

and magnetic resonance imaging techniques.7 I Doherty M. 'Chondroprotection' by non- Although process and outcome measures Eventually the accuracy and the methodology steroidal anti-inflammatory drugs. Ann Rheun may correlate positively, the former cannot be

Dis 1989; 48: 619-21. Ann Rheum Dis: first published as 10.1136/ard.49.5.338-c on 1 May 1990. Downloaded from associated' with these techniques will improve 2 Lohmander L S, Proteoglycans of joint cartilage: used to predict the latter.2' In osteoarthritis, sufficiently to allow their routine clinical structure, function, turnover and role as particularly, there is marked discordance application, but in the short term we can only markers of joint disease. In: Dixon J S, Bird between symptoms, signs, and radiographic or rely on data generated from animal studies to H A, eds. Clinical rheumatology: biochemical pathological abnormality: an association aspects of rheumatic diseases. Vol 2, No 1. guide us in selecting the drugs of potential London: Saunders, 1988. between any process markers that we have and clinical interest. 3 Lohmander L S, Dahlberg L, Ryd L, Heinegird outcome remains to be established. Although I Although we all agree that animal models D. Increased levels of proteoglycan fragments share Dr Ghosh's enthusiasm for continuing in joint fluid after knee injury. Arthritis Rhewn of osteoarthritis are imperfect, they do permit 1989; 32: 1434-42. work investigating biochemical markers of a direct assessment of a drug's effect on a 4 Heinegird D, Inerot S, Weislande J, Lindblad joint damage/repair and improved assessment variety of joint features which are relevant to G. A method for quantitation of cartilage of structure, we must remain aware of the proteoglycan structures liberated to the synovial limitations of such (predominantly process) the human condition. These effects include fluid during developing degenerative joint not only changes in cartilage integrity but disease. Scand J Clin Lab Invest 1985; 45: measures. Again as previously discussed,' chondrocyte metabolic activity, subchondral 421-7. undue emphasis on cartilage (cfbone, capsule, blood circulation, osteophyte formation, 5 Thonar E J M, Lenz M E, Klintworth G K, et al. ligament, muscle) may prove inappropriate. Quantitation of keratan sulphate in blood as a synovial cell metabolism, and biosynthesis of marker of cartlage catabolism. Arthritis Rheum Although common sense dictates that cartilage hyaluronic acid, all of which should be in- 1985; 28: 1367-76. loss is bad, this is not an isolated change cluded in anydefinition ofchondroprotection.8 6 Sweet M B E, Coelho A, Schnitzler C M, et al. within the joint and need not be the crucial Serum keratan sulphate levels in osteoarthritis factor determining outcome. For example, we Furthermore, most drugs used in clinical patients. Arthritis Rheum 1988; 31: 648-52. medicine today were selected from animal 7 Sabiston C P, Adam M E, Li D K B. Magnetic know that despite gross cartilage loss most studies in which the drugs showed activity resonance imaging of osteoarthritis: correlation osteoarthritic joints, especially in the hand,5 which may, or may not be directly applicable with gross pathology using an experimental function normally with minimal or only model. Orthop Res 1987; 5: 164-72. to human disease. If this practice is to be 8 Ghosh P, Wells C, Smith M, Hutadilok N. periodic symptoms. In respect of intervention criticised the criticism should perhaps be Chondroprotection, myth or reality-an experi- in osteoarthritis the whole joint (not just directed at those pharmaceutical companies mental approach. Semin Arthitis Rheum 1990; selected, individual biochemical or structural that have been reluctant to deviate from 19 (suppl 1): 3-9. change) and whole patient need to be con- traditional methods of drug discovery, for sidered. there exists a plethora of 'super aspirins' and it Sir: I am sure that Dr Ghosh and I are in From a clinical standpoint, therefore, is more by luck than design that some of these general agreement about the many issues symptoms and functional status remain the molecules seem to show chondroprotective relating to the effects of non-steroidal anti- standard by which to judge long term success activity. inflammatory drugs on osteoarthritic and or failure in osteoarthritis. Investigation of For more than 80 years the medical com- normal joints, and I welcome his comments on accompanying structural, physiological, and munity has been content to accept the products this subject. biochemical changes (in animals and man) provided by the pharmaceutical industry for As mentioned in the 1989 leader,' in vitro may improve our understanding ofits process, the treatment of musculoskeletal disorders. and animal work have given valuable insight and perhaps suggest means of prevention. If Today, as a result of the debate stimulated by into possible mechanisms of joint injury and found to equate with outcome, such process laboratory studies, this attitude is changing repair, and stimulated interest in the effects, changes may additionally prove useful in and doctors are rightly questioning the long either detrimental or beneficial, of currently monitoring effects of intervention. term efficacy of their NSAIDs, particularly available drugs on the joints (not to mention the deleterious side effects which may the gut) of our patients. Nevertheless, I would MICHAEL DOHERTY reaffirm the need for caution in extrapolating Rhewnatolog Unit accompany their use. City Hospital The influence of the advertising industry too rigidly such laboratory derived data to the Notingham NG5 IPB notwithstanding, the choice of an NSAID clinical situation of human osteoarthritis. http://ard.bmj.com/ should be made by judicious evaluation of the When considering the natural history or intervention of any laboratory and clinical data available at the modification by health 1 Doherty M. 'Chondroprotection' by non-steroidal time. Although these data may be imperfect disease process, it is important to distinguish anti-inflammatory drugs. Amn Rheum Dis 1989; they can provide the stimulus for further process from outcome measures.2 Process 48: 619-21. that measures, clinical or investigative, primarily 2 Williamson J W. Evaluating quality of patient investigations and it is only by this means care: a strategy relating outcome and process we can hope to generate the ground swell of relate to mechanisms of disease causation assessment. JAMA 1971; 218: 564-9. opinion necessary to change prevailing atti- and tissue response, reflecting such aspects 3 Bellamy N, Buchanan W W. Outcome measure- tudes and promote new therapeutic advances as inflammation, immune reaction, tissue ment in osteoarthritis clinical trials: the case for on September 27, 2021 by guest. Protected copyright. damage/synthesis/repair, and structural standardisation. Clin Rheumatol 1984; 3: in this much neglected field. change. 293-303. Outcome measures, by contrast, relate more 4 Liang M H, Cullen K E, Larson M G. Measuring PETER GHOSH to the meaningful effects of disease on the function and health status in rheumatic disease Raymond Purves Research Laboratory individual, reflecting such aspects as impaired clinical trials. Clin Rheum Dis 1983; 9: 531-9. (University ofSydney) 5 Pattrick M, Aldridge S, Hamilton E, Manhire A, Royal North Shore Hospital ofSydney function, suffering, morbidity, and mortality; Doherty M. A controlled study of hand func- St Leonards,/New South Wales 2065 such measures by their nature are predomi- tion in nodal and erosive osteoarthritis. Ann Australia nantly clinical. Rheun Dis 1989; 48: 978-82.