RHEUMATOLOGY AND REHABILITATION Vol. XVI
August 1977
'
No. 3
REPEATED CORTICOSTEROID INJECTIONS INTO KNEE JOINTS BY H. W. BALCH, J. M. C. GIBSON, A. F. EL-GHOBAREY, L. S. BAIN AND M. P. LYNCH Rheumatology Unit, City Hospital, Aberdeen
SUMMARY The effect of intra-articular injections of corticosteroids repeated over a period extending from four to 15 years on the radiological appearances of knee joints affected by rheumatoid arthritis and osteoarthritis has been studied. In 65 cases, the X-ray films of 15 showed no deterioration, 38 showed minimal or moderate deterioration, 10 showed marked deterioration and only 2 showed gross deterioration. The results do not support the contention that repeated intra-articular injections of corticosteroids will inevitably lead to rapid joint destruction. The authors are of the opinion that intraarticular injections of corticosteroids, if used judiciously, have an important part to play in the management of chronic arthritis. MOST rheumatologists axe reluctant to prescribe systemic corticosteroids in the treatment of rheumatoid disease because of the well-known hazards associated with the longterm use of these drugs. On the other hand, many consider that intra-articular injection with corticosteroids is an extremely valuable form of treatment which appears to have withstood the test of time. It is now twenty-five years since Hollander and his colleagues (1951) in America first reported the dramatic improvement which followed the injection of hydrocortisone acetate into the inflamed knees of subjects with rheumatoid arthritis. Subsequently, Hollander and his colleagues obtained the same improvement when they injected painful and swollen osteoarthritic knees. In the intervening years the procedure has become standard practice in many rheumatology units, although some orthopaedic surgeons have expressed grave warnings about possible dangers associated with this form of treatment. Chandler and Wright (1958) observed marked radiological evidence of deterioration in 13 out of 25, knee joints treated with repeated intra-articular injections of corticosteroids. Steinberg et al. (1962) reported rapid deterioration both clinically and radiologically in the knee joint of a 51-year-old male which had received 22 injections over a Accepted for publication January 1977. Requests for reprints to Dr. H. W. Balch. 137
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
ORIGINAL PAPER
138
RHEUMATOLOGY AND REHABILITATION VOL. XVI NO. 3
MATERIAL AND METHOD During the last twenty years many patients have received repeated injections to the knee joints over prolonged periods of time. The presence of pain not relieved by other standard forms of treatment is considered to be an indication for a corticosteroid injection. Significant relief of that pain for a reasonable period of time is taken as an indication for repeating an injection. The material used for injection has varied over the twenty years. Initially hydrocortisone acetate 50 mg was used. Then when prednisolone tbutyl acetate became available this analogue in a dose of 40 mg was used for some time. Latterly 6-methyl prednisolone (Depo-Medrone) 40 mg has been used extensively as well as triamcinolone hexacetonide 20 mg. It was decided to examine radiographically the knees of all patients attending for intra-synovial injections who had received repeated injections for four years or more.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
period of two years between August 1955 and November 1957. On several occasions in 1955 four injections of 50 mg of hydrocortisone acetate were given in one month. The patient did not consult the authors until 1961 when he was found to have a severely disorganized knee confirmed at operation (arthrodesis). However, in the period 1957-61 he had received an unspecified amount of phenylbutazone and hydroxychloroquine sulphate. Bentley and Goodfellow (1969) reported the rapid disorganization occurring in the knee joint of a 73-year-old woman after repeated intra-articular injections. This patient received twelve injections of 50 mg of hydrocortisone acetate into her left knee at weekly intervals which gave marked symptomatic improvement. In view of this success a course of injections of 50 mg of hydrocortisone acetate was given to both knees every two weeks for a further twenty injections, i.e. over a total period of 14 months from October 1966. In January 1968 the patient was suffering severe constant pain and both knees were markedly disorganized clinically and radiologically and this was confirmed at operation. On the basis of this evidence these authors felt so strongly about the hazards that they stated categorically that 'the case against multiple injections is so strong that the practice should in our opinion be discarded, which implies that even a single injection requires strong justification'. Intra-articular injections of corticosteroids have been and still are used extensively in the Rheumatology Unit in Aberdeen but this form of treatment is only considered to be appropriate when used in conjunction with other well recognized forms of treatment —an opinion which has always been stressed by Hollander. The indications and contraindications are clearly outlined by Hollander and McCarty (1972) and in a series of articles by Kendall (1962a, b, 1963). In the Rheumatology Unit at Aberdeen, intrasynovial corticosteroid injections are given to relieve pain and are only repeated if pain has been relieved for a significant period of time. Relief of pain for ten days or more is considered worthwhile and relief is often obtained for much longer periods. We are strongly opposed to the practice of prescribing injections in predetermined courses and believe that the operator should make a clinical reappraisal of the effect and duration of relief of a previous injection before repeating the procedure. In view of widely differing attitudes and opinions, the reports of rapid destruction of joint cartilage referred to above and the strongly worded condemnation of the procedure expressed by some authors we decided to investigate this problem more closely. Accordingly, we arranged to carry out a retrospective study on all patients who were currently receiving intra-articular corticosteroid injections and had done so over a prolonged period, with particular reference to the radiographic appearances.
BALCH ETAL.: REPEATED CORTICOSTEROID KNEE INJECTIONS
139
RESULTS The radiographs of 65 knee joints were examined. Of these, 35 were of patients suffering from rheumatoid arthritis and 30 had osteoarthritis. Repeated intrasynovial injections had been given over a period varying from four to 15 years. The minimum number of injections given was 15 over a period of four years and the maximum was 167 injections in a period of twelve years. The interval between injections was not less than four weeks (with the exception of two patients and frequently the period was considerably longer). A total of 4412 injections was given. The final radiographic categories charted against the number of injections given is shown in the Table. Of the 65 films of knee joints examined, 15 showed no obvious TABLE RADIOGRAPHIC CHANGES CHARTED AGAINST NUMBER OF INJECTIONS
Radiographic change
None Minimal Moderate Marked Gross
Number of injections 15-49
50-99
100-149
>150
9 12 6 5 0
3 3 7 2 2
1 4 4 1 0
2 2 0 2 0
radiological deterioration (two patients in this category had received 154 injections), 21 showed minimal, 17 moderate and 10 marked deterioration. Only two knee joints showed gross radiological changes after 82-85 injections given over a period of seven years. These were in the same patient. DISCUSSION One of the most comprehensive descriptive accounts of intra-synovial corticosteroid therapy is that given by Hollander and McCarty in the 1972 edition of the textbook Arthritis and Allied Conditions. For 25 years Hollander has remained one of the most authoritative and enthusiastic advocates of this form of therapy but he has always emphasized that it must only be considered as a useful adjunct to a co-ordinated plan of treatment. He agrees that he has observed rapid deterioration occurring occasionally
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
The up-to-date films of the involved joints were carefully compared with earlier films for any evidence of deterioration and in particular for evidence of Charcot's type joint destruction. This scrutiny was carried out by two independent assessors, one a physician and the other an orthopaedic surgeon. The assessors decided on a 5-point scale to illustrate their findings: 0=no deterioration 1 = minimal deterioration; slight narrowing in any compartment of the joint 2=moderate deterioration; moderate narrowing in any compartment 3=marked deterioration; marked narrowing with some collapse of a condyle and/or lateral subluxation 4=gross deterioration; Charcot's type joint
140
RHEUMATOLOGY AND REHABILITATION VOL. XVI NO. 3
REFERENCES
G. and GOODFELLOW, J. W. (1969) "Disorganisation of the Knees Following Intraarticular Hydrocortisone Injections". J. Bone Jt. Surg. 51B, 498-502. CHANDLER, G. N., JONES, D. T., WRIGHT, V. and HARFALL, S. J. (1959) "Charcot's Arthropathy Following Intra-articular Hydrocortisone". Br. Med. J. 1,952-3. and WRIGHT, V. (1958) "Deleterious Effect of Intra-articular Hydrocortisone". Lancet ii, 661-3. HOLLANDER, J. L., BROWN, E. M., JESSAR, R. A. and BROWN, C. Y. (1951) "Hydrocortisone and Cortisone Injected into Arthritis Joints". /. Am. Med. Assoc. 147,1629-35. and MCCARTHY, D. J. (1972) Arthritis and Allied Conditions. 8th ed. pp. 517-34. KENDALL, P. HUME (1962a) Ann. Phys. Med. 7,302. (19626) Ann. Phys. Med. 8,359 (1963) Ann. Phys. Med. 1,31. STEINBERG, C. L. R., DUTHIE, R. B. and PIVA, A. E. (1962) "Charcot-like Arthropathy Following Intra-articular Hydrocortisone". /. Am. Med. Assoc. 181,851-4. BENTLEY,
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
in joints but in his own series involving more than 8000 patients and some 250 000 injections the incidence has been less than- one per cent. Since we made this survey we have seen the disintegration of a knee joint in a woman of 75 years suffering from osteoarthritis, after only two injections of 80 mg of 6-methyl prednisolone given four weeks apart after' aspiration and examination of a synovial effusion. In our own series comprising some 80 000 injections over a period of twenty years the incidence of rapid joint damage has remained at less than one per cent. The reports by Chandler and various other investigators describing the production of 'Charcot type arthropathy' following repeated intra-articular injections of corticosteroids undoubtedly focused attention on one of the possible hazards associated with this technique. These reports have led to a more critical evaluation of this form of treatment but the hazard has probably been overemphasized. We strongly believe that intrasynovial injections of potent corticosteroids should never be given in courses of a predetermined number of injections at short intervals. We would agree with Hollander that the interval between injections should not be less than four weeks and before any repeat injection is given a careful clinical reappraisal of the effect achieved and the state of the joint should be made. In our present investigation we have found no real evidence to support the suggestion that repeated intra-articular injections will inevitably lead to rapid joint destruction. We are well aware of the possible hazard but nevertheless we are firmly of the opinion that this form of treatment has a very useful and important part to play in the overall management of patients suffering from chronic arthritis.
August 1977
'
No. 3
REPEATED CORTICOSTEROID INJECTIONS INTO KNEE JOINTS BY H. W. BALCH, J. M. C. GIBSON, A. F. EL-GHOBAREY, L. S. BAIN AND M. P. LYNCH Rheumatology Unit, City Hospital, Aberdeen
SUMMARY The effect of intra-articular injections of corticosteroids repeated over a period extending from four to 15 years on the radiological appearances of knee joints affected by rheumatoid arthritis and osteoarthritis has been studied. In 65 cases, the X-ray films of 15 showed no deterioration, 38 showed minimal or moderate deterioration, 10 showed marked deterioration and only 2 showed gross deterioration. The results do not support the contention that repeated intra-articular injections of corticosteroids will inevitably lead to rapid joint destruction. The authors are of the opinion that intraarticular injections of corticosteroids, if used judiciously, have an important part to play in the management of chronic arthritis. MOST rheumatologists axe reluctant to prescribe systemic corticosteroids in the treatment of rheumatoid disease because of the well-known hazards associated with the longterm use of these drugs. On the other hand, many consider that intra-articular injection with corticosteroids is an extremely valuable form of treatment which appears to have withstood the test of time. It is now twenty-five years since Hollander and his colleagues (1951) in America first reported the dramatic improvement which followed the injection of hydrocortisone acetate into the inflamed knees of subjects with rheumatoid arthritis. Subsequently, Hollander and his colleagues obtained the same improvement when they injected painful and swollen osteoarthritic knees. In the intervening years the procedure has become standard practice in many rheumatology units, although some orthopaedic surgeons have expressed grave warnings about possible dangers associated with this form of treatment. Chandler and Wright (1958) observed marked radiological evidence of deterioration in 13 out of 25, knee joints treated with repeated intra-articular injections of corticosteroids. Steinberg et al. (1962) reported rapid deterioration both clinically and radiologically in the knee joint of a 51-year-old male which had received 22 injections over a Accepted for publication January 1977. Requests for reprints to Dr. H. W. Balch. 137
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
ORIGINAL PAPER
138
RHEUMATOLOGY AND REHABILITATION VOL. XVI NO. 3
MATERIAL AND METHOD During the last twenty years many patients have received repeated injections to the knee joints over prolonged periods of time. The presence of pain not relieved by other standard forms of treatment is considered to be an indication for a corticosteroid injection. Significant relief of that pain for a reasonable period of time is taken as an indication for repeating an injection. The material used for injection has varied over the twenty years. Initially hydrocortisone acetate 50 mg was used. Then when prednisolone tbutyl acetate became available this analogue in a dose of 40 mg was used for some time. Latterly 6-methyl prednisolone (Depo-Medrone) 40 mg has been used extensively as well as triamcinolone hexacetonide 20 mg. It was decided to examine radiographically the knees of all patients attending for intra-synovial injections who had received repeated injections for four years or more.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
period of two years between August 1955 and November 1957. On several occasions in 1955 four injections of 50 mg of hydrocortisone acetate were given in one month. The patient did not consult the authors until 1961 when he was found to have a severely disorganized knee confirmed at operation (arthrodesis). However, in the period 1957-61 he had received an unspecified amount of phenylbutazone and hydroxychloroquine sulphate. Bentley and Goodfellow (1969) reported the rapid disorganization occurring in the knee joint of a 73-year-old woman after repeated intra-articular injections. This patient received twelve injections of 50 mg of hydrocortisone acetate into her left knee at weekly intervals which gave marked symptomatic improvement. In view of this success a course of injections of 50 mg of hydrocortisone acetate was given to both knees every two weeks for a further twenty injections, i.e. over a total period of 14 months from October 1966. In January 1968 the patient was suffering severe constant pain and both knees were markedly disorganized clinically and radiologically and this was confirmed at operation. On the basis of this evidence these authors felt so strongly about the hazards that they stated categorically that 'the case against multiple injections is so strong that the practice should in our opinion be discarded, which implies that even a single injection requires strong justification'. Intra-articular injections of corticosteroids have been and still are used extensively in the Rheumatology Unit in Aberdeen but this form of treatment is only considered to be appropriate when used in conjunction with other well recognized forms of treatment —an opinion which has always been stressed by Hollander. The indications and contraindications are clearly outlined by Hollander and McCarty (1972) and in a series of articles by Kendall (1962a, b, 1963). In the Rheumatology Unit at Aberdeen, intrasynovial corticosteroid injections are given to relieve pain and are only repeated if pain has been relieved for a significant period of time. Relief of pain for ten days or more is considered worthwhile and relief is often obtained for much longer periods. We are strongly opposed to the practice of prescribing injections in predetermined courses and believe that the operator should make a clinical reappraisal of the effect and duration of relief of a previous injection before repeating the procedure. In view of widely differing attitudes and opinions, the reports of rapid destruction of joint cartilage referred to above and the strongly worded condemnation of the procedure expressed by some authors we decided to investigate this problem more closely. Accordingly, we arranged to carry out a retrospective study on all patients who were currently receiving intra-articular corticosteroid injections and had done so over a prolonged period, with particular reference to the radiographic appearances.
BALCH ETAL.: REPEATED CORTICOSTEROID KNEE INJECTIONS
139
RESULTS The radiographs of 65 knee joints were examined. Of these, 35 were of patients suffering from rheumatoid arthritis and 30 had osteoarthritis. Repeated intrasynovial injections had been given over a period varying from four to 15 years. The minimum number of injections given was 15 over a period of four years and the maximum was 167 injections in a period of twelve years. The interval between injections was not less than four weeks (with the exception of two patients and frequently the period was considerably longer). A total of 4412 injections was given. The final radiographic categories charted against the number of injections given is shown in the Table. Of the 65 films of knee joints examined, 15 showed no obvious TABLE RADIOGRAPHIC CHANGES CHARTED AGAINST NUMBER OF INJECTIONS
Radiographic change
None Minimal Moderate Marked Gross
Number of injections 15-49
50-99
100-149
>150
9 12 6 5 0
3 3 7 2 2
1 4 4 1 0
2 2 0 2 0
radiological deterioration (two patients in this category had received 154 injections), 21 showed minimal, 17 moderate and 10 marked deterioration. Only two knee joints showed gross radiological changes after 82-85 injections given over a period of seven years. These were in the same patient. DISCUSSION One of the most comprehensive descriptive accounts of intra-synovial corticosteroid therapy is that given by Hollander and McCarty in the 1972 edition of the textbook Arthritis and Allied Conditions. For 25 years Hollander has remained one of the most authoritative and enthusiastic advocates of this form of therapy but he has always emphasized that it must only be considered as a useful adjunct to a co-ordinated plan of treatment. He agrees that he has observed rapid deterioration occurring occasionally
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
The up-to-date films of the involved joints were carefully compared with earlier films for any evidence of deterioration and in particular for evidence of Charcot's type joint destruction. This scrutiny was carried out by two independent assessors, one a physician and the other an orthopaedic surgeon. The assessors decided on a 5-point scale to illustrate their findings: 0=no deterioration 1 = minimal deterioration; slight narrowing in any compartment of the joint 2=moderate deterioration; moderate narrowing in any compartment 3=marked deterioration; marked narrowing with some collapse of a condyle and/or lateral subluxation 4=gross deterioration; Charcot's type joint
140
RHEUMATOLOGY AND REHABILITATION VOL. XVI NO. 3
REFERENCES
G. and GOODFELLOW, J. W. (1969) "Disorganisation of the Knees Following Intraarticular Hydrocortisone Injections". J. Bone Jt. Surg. 51B, 498-502. CHANDLER, G. N., JONES, D. T., WRIGHT, V. and HARFALL, S. J. (1959) "Charcot's Arthropathy Following Intra-articular Hydrocortisone". Br. Med. J. 1,952-3. and WRIGHT, V. (1958) "Deleterious Effect of Intra-articular Hydrocortisone". Lancet ii, 661-3. HOLLANDER, J. L., BROWN, E. M., JESSAR, R. A. and BROWN, C. Y. (1951) "Hydrocortisone and Cortisone Injected into Arthritis Joints". /. Am. Med. Assoc. 147,1629-35. and MCCARTHY, D. J. (1972) Arthritis and Allied Conditions. 8th ed. pp. 517-34. KENDALL, P. HUME (1962a) Ann. Phys. Med. 7,302. (19626) Ann. Phys. Med. 8,359 (1963) Ann. Phys. Med. 1,31. STEINBERG, C. L. R., DUTHIE, R. B. and PIVA, A. E. (1962) "Charcot-like Arthropathy Following Intra-articular Hydrocortisone". /. Am. Med. Assoc. 181,851-4. BENTLEY,
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Manchester on May 18, 2015
in joints but in his own series involving more than 8000 patients and some 250 000 injections the incidence has been less than- one per cent. Since we made this survey we have seen the disintegration of a knee joint in a woman of 75 years suffering from osteoarthritis, after only two injections of 80 mg of 6-methyl prednisolone given four weeks apart after' aspiration and examination of a synovial effusion. In our own series comprising some 80 000 injections over a period of twenty years the incidence of rapid joint damage has remained at less than one per cent. The reports by Chandler and various other investigators describing the production of 'Charcot type arthropathy' following repeated intra-articular injections of corticosteroids undoubtedly focused attention on one of the possible hazards associated with this technique. These reports have led to a more critical evaluation of this form of treatment but the hazard has probably been overemphasized. We strongly believe that intrasynovial injections of potent corticosteroids should never be given in courses of a predetermined number of injections at short intervals. We would agree with Hollander that the interval between injections should not be less than four weeks and before any repeat injection is given a careful clinical reappraisal of the effect achieved and the state of the joint should be made. In our present investigation we have found no real evidence to support the suggestion that repeated intra-articular injections will inevitably lead to rapid joint destruction. We are well aware of the possible hazard but nevertheless we are firmly of the opinion that this form of treatment has a very useful and important part to play in the overall management of patients suffering from chronic arthritis.
