Rheumatology and Rehabilitation, 1975, 14, 244
ORIGINAL PAPER
SYNOVITIS IN POLYMYALGIA RHEUMATICA BY D. R. F. HENDERSON*, C. R. TRIBE AND A. ST. J. DIXON Guy's Hospital, London; Department of Pathology, Southmead Hospital, Bristol; and Royal National Hospital for Rheumatic Diseases, Bath
SYNOVITIS is infrequent in polymyalgia rheumatica (PMR). It is often the absence of joint involvement in patients with proximal limb-girdle stiffness, constitutional illness and a rapid erythrocyte sedimentation rate (e.s.r.) that suggests this diagnosis. However, it does occasionally occur, for example, in four out of sixty-five patients reported by Dixon (1970). Non-specific synovitis has also been described in biopsy studies from the shoulder and sternoclavicular joints of three series of patients (Gordon, Rennie and Branwood, 1964; Andrews, 1965; and Bruk, 1967). We describe arthroscopy, synovial fluid analysis and biopsy observations in four patients with PMR and synovitis of the knee. One also had sacroiliac joint changes and one further patient had involvement of the wrist and shoulder. These findings have been related to a series of 88 consecutive patients with PMR (with and without temporal arteritis) seen and treated in Bath during 1965 and 1973. The criteria for the diagnosis of PMR (Dixon et al., 1966) required, first, the presence of intense stiffness of proximal limb movements especially after resting, a raised e.s.r. (Westergren) and a rapid response to corticosteroids; and, second, the absence of rheumatoid arthritis, systemic lupus erythematosis, polymyositis, carcinomatosis or other disease which might present in a similar manner. These were excluded by consistently negative results in a battery of appropriate screening tests, muscle biopsy and radiography which will not be further detailed, apart from those relevant to synovitis. As evidence of synovitis we have accepted swelling of the joints or tendon sheaths containing fluid with an increased number of white cells, or synovial biopsy showing inflammation. Stiff, limited or painful joint movement and small effusions of clear fluid were not accepted as indicative of synovitis.
PATIENTS PATIENT 1
Mrs. A. A. at the age of 67 rapidly developed pain in the shoulder muscles, buttocks and thighs which prevented walking. Morning stiffness and malaise were present. The * Present address: The Queen Elizabeth Hospital, Woodville, South Australia 5011. Accepted for publication December 1974. 244
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SUMMARY Synovitis was observed in 13 out of 88 consecutive patients with polymyalgia rheumatica. It is described in detail in five patients, on the basis of clinical and radiological observations, joint aspiration, arthroscopy and biopsy. The synovitis of polymyalgia rheumatica cannot be distinguished histologically or at arthroscopy from the appearance seen in mild rheumatoid arthritis. Clinically, however, the synovitis of polymyalgia rheumatica is mild, transient and confined to one or two joints or tendon sheaths. It is not followed by joint deformity or by radiological erosive changes in the bone ends. It may occur at any stage of the disease but particularly at its onset, or when the dose of corticosteroid treatment is reduced.
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PATIENT 2
Mrs. N. W. at the age of 54 developed pain and stiffness in the shoulders, neck and arms following surgery for bilateral hallux valgus. The e.s.r. was 53 mm/h. Prednisolone 15 mg/day improved the symptoms. The dose was reduced over the next two years. Age 60, she again developed fever and limb stiffness with painful swelling of the knees with a popliteal cyst. Prednisolone 7.5 mg was given and she was admitted to hospital. Hb 11.5 g/dl; e.s.r. 120 mm/h; serum proteins 8 g/dl (Alb. 3.2, Glob. 4.8) with a diffuse increase in the y-globulin. The Rose test was negative in all but one of many estimations. Radiography showed erosion of the symphysis pubis. Inflammatory synovial fluid was removed from one knee. The patient improved with rest and prednisolone in the same dosage but symptoms returned after discharge. Age 61 she was readmitted with synovitis of the right knee and stiffness of shoulder movement without swelling; Hb 10.4 g/dl; e.s.r. 100 mm/h; Antinuclear factor absent. The histocompatability antigen HLA W 27 was absent. Radiography showed increase in the sclerotic changes in the symphysis pubis and erosion and sclerosis of the left sacroiliac joint. Attempts to reduce the daily dose of prednisolone below 15 mg resulted in a return of the symptoms and raised e.s.r. At age 62, arthroscopy of the knee confirmed synovitis.
PATIENT 3
Mrs. M.S., an art dealer aged 68, developed PMR without joint swelling which responded to prednisolone 12.5 mg/day. The dose was gradually reduced to 3 mg/day with regular supervision and control. At age 70, having been active, vigorous and regularly at work, she relapsed, with pain and swelling of the right knee from which inflammatory joint fluid was withdrawn. Synovitis responded temporarily to an injection of hydrocortisone acetate (40 mg). One month later she had a typical episode of temporal arteritis associated with temporal scalp pain, tenderness over the temporal arteries and headache. Arthroscopy of the right knee revealed erythema and swollen polypoid villi. Some fibrin was present. The cartilage showed only mild degenerative changes.
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joints were normal. She appeared myxoedematous. Investigations: Hb 10.0 g/dl; e.s.r. 103 mm/h; Rose test for rheumatoid factor negative on five occasions; albumin 3.9 g/dl; globulin 3.2 g/dl, alpha-2 globulins increased; protein-bound iodine 0.5 /*g/dl; cholesterol 340 g/dl. Thyroxine 0.1 g/day corrected her hypothyroidism which caused no further concern. Prednisolone 15 mg/day controlled her PMR and the e.s.r. fell to 10 mm/h. The dose was progressively reduced but at eighteen months at 2.5 mg/day symptoms recurred, followed after two months by an effusion in the left knee complicated in turn by popliteal swelling and acute synovial rupture. Her condition responded to rest and methylprednisolone 16 mg/day. Three months later, again following reduction of the dose, pain and stiffness returned, both knees swelled and the e.s.r. rose to 83 mm/h. Synovial fluid aspirated from the knee was turbid, of low viscosity and contained 85% polymorphs and 15% lymphocytes. The synovial Rose test was weakly positive. At arthroscopy the synovium showed erythema, oedema and polyp formation. The articular surface showed mild degenerative changes. Under continued observation, the knees became normal. No other joints have been affected and radiographs have shown only mild arthrosis.
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RHEUMATOLOGY AND REHABILITATION VOL. XIV NO. 4 PATIENT 4
PATIENT 5
Mr. G.H-F., aged 76, noted the rapid onset of generalized stiffness particularly affecting the shoulders, buttocks and thighs. From being remarkably active for his age he found himself neither able to dress unaided nor to rise unassisted from an easy-chair. A small swelling in the right subdeltoid bursa was aspirated producing slightly turbid inflammatory fluid. Inflammatory swelling of the right common extensor tendon sheath at the wrist was also present. There was a mild anaemia (Hb 10.8 g/dl) a raised e.s.r. (50 mm/h) and a negative test for rheumatoid factor. All other investigations were negative. The evidence of synovitis disappeared under treatment with 5 mg/day of prednisolone and this dose was steadily reduced and finally withdrawn after two years. At followup aged 80, he remained well and has regained his previous vigour, off all treatment and without evidence of synovitis. REFERENCE SERIES A reference series of 88 patients with PMR seen in Bath in the years 1965 to 1971 (part of a series previously described to a meeting of the British Medical Association, Dixon, 1970) included 21 patients with a strong clinical evidence of giant cell arteritis confirmed by positive biopsy in six, cranial arteriogram in one or the prior development of sudden blindness in two. Of these 88 patients, 70 showed no evidence of joint disease at any time. Five further patients had osteoarthrosis affecting the knees without inflammatory changes, diagnosed on clinical grounds and confirmed in all by aspiration of a small amount of water-clear, viscid joint fluid. Thus, only 13 out of 88 showed any evidence of inflammatory synovitis. In nine, the knee showed synovitis confirmed in four by aspiration of turbid fluid of a low viscosity (and incidently negative for rheumatoid factor in three out of three tested) and, in six, there was a generalized oedema of the hands to which synovitis of the wrist and finger joints appeared to be contributing (four of these also had synovitis of the knee at the same time). One patient who had previously had a positive temporal artery biopsy subsequently went on to develop classical seropositive rheumatoid arthritis; the only one to do so in this series (this could be expected from the
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Mr. E.S., a shopkeeper aged 60, noted the rapid onset of pain and immobilizing stiffness in the shoulders, buttocks and thighs. Shoulders, elbows, knee and wrists were limited in range of movement. No joint was swollen. The Hb was 12 g/dl; the e.s.r. was 87 mm/h; rheumatoid factor was absent. He was treated with prednisolone 10 mg daily with immediate improvement and the e.s.r. fell to 18 mm/h. Prednisolone was reduced gradually to 5 mg daily and maintained at from 5 to 7 mg a day until aged 63 when dose reduction was again attempted. At 3 mg/day, he noted fatigue accompanied by painful swelling and stiffness of the knees, The left ankle was warm with some swelling. Hb 11.8 g/dl; e.s.r. 79 mm/h; the WCC 9000/mm3, rheumatoid factor absent. Arthroscopy of the right knee disclosed inflammatory synovial fluid and synovium with mild degenerative changes in the articular cartilage. Prednisolone was increased to 5 mg/day with improvement and the e.s.r. fell from 80 to 41 mm/h. When followed up four years after the onset of his illness and six months after the esisode of synovitis he remained well and was clinically normal.
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prevalence of rheumatoid arthritis in the population). One patient (patient 5 in this report) developed transient synovitis with effusions of the shoulder and extensor tendon sheath and one developed symptomless radiological evidence of nonankylosing sacroiliac arthritis (Andrews, 1965) similar to that seen in Patient 2.
DISCUSSION The frequency of joint involvement in reported series of patients with PMR is shown in the Table and ranges from none to two thirds. The lowest frequency comes from authors who consider that the presence of synovitis precludes the diagnosis of PMR, e.g. Forestier and Certoncini, 1963; Davidson, Spiera and Plotz, 1966. The larger figures come from a series (Bruk, 1967) in which the criteria for admission included central joint tenderness and the criteria for synovitis included palpable synovial thickening or demonstrable synovial effusion. These criteria may have been too permissive (small effusions are common in the knees of normal elderly people). However, there are a number of acceptable reports of synovitis supported in some instances by synovial biopsy or synovial fluid analysis. Taking into account differences in methodology, the frequency lies between 15 and 50%. The joints most frequently affected are the knees, wrist,fingersand shoulders, in that order. The arthritis is transient, lasting days or weeks and appears to respond well to local or systemic corticosteroid therapy,
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HISTOLOGICAL STUDIES Synovial biopsies obtained under direct vision at arthroscopy from the knee-joints of Patients 1-4 were examined. In order not to bias the interpretations, the synovial biopsy specimens were examined "blind" amongst other synovial biopsy specimens obtained at arthroscopy from 21 patients with proven rheumatoid arthritis (RA) which were being studied as part of an attempt to correlate biopsy appearances with the course and progress of the patients' arthritis (Henderson, Jayson and Tribe, 1975). The histclogical appearances varied widely among these patients with RA and no relation could be found between a range of histological features on the one hand and the clinical, radiological and arthroscopicfindingson the other. Furthermore, all the histological features of the synovium in our patients with PMR synovitis could be accommodated within this wide range of appearances in these patients with RA. These changes were essentially similar in all four instances and consisted of synovial tissue hyperplasia, hyperaemia and a moderate mixed cellular infiltrate of lymphocytes and plasma cells in the subsynovium. The synovial hyperplasia varied in thickness from three to five cells wide and in all the biopsies had a loosefibrillaryoedematous appearance with wide separation of the nuclei. The degree of cellular infiltration of the subsynovium varied considerably in different areas of the biopsies. It tended to be superficial and the number of plasma cells and lymphocytes was usually about equal. In only one biopsy was there any attempt at lymph follicle formation. In all biopsies, the stroma contained many small vessels. Certain histological features did seem to be more common in PMR than in RA. These were: 1. The synovial lining hyperplasia was always three cells wide or more and often had a peculiar oedematous fibrillary appearance. 2. The stromal infiltrate tended to be superficial and was composed of equal numbers of plasma cells and lymphocytes. 3. Iron deposition was very mild and small amounts only were found in 1 out of 4 of these patients as compared with 10 out of 21 patients with rheumatoid arthritis who had mild to severe iron deposition.
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TABLE: COMPARISON OF THB FREQUENCY OF JOINT INVOLVEMENT AND SYNOVITIS FOUND IN PATIENTS WITH POLYMYALOIA RHEUMATICA
Author
Year No. of No. with Knees patients synovitis
Kersley
1956
13
3 (23%)
Gordon
I960
21
6 (29%)
Gordon el al.
1964
6
Forestier and Certoncini
1953
Bagratini
1963
50
Andrews
1965
37
Kogstad
1965
70
de Seze el al.
1965
45
Wilske and Healy
1967
18
8 (44%)
8
Bruk
1967
80
55 (69%)
40
Bell and Klinefelter Handa el al.
1967
29
11(38%)
1969
12«
6(50%)
Kaiser
1969
5
Dixon el al.
1966
31
Present series
4
6 (100%)
Other joints
Tapped
MCP 1 PIP1
1
Fluid
Biopsy
Radiography
Many polymorphs. Few Mononudear cells 6 Capsule biopsies show nospecific inflammation
Shoulders
0
88
8 (16%)
1 Normal
Sacroiliac symphysis pubis 11 (16%)
7 Stemodavicular 6 Abnormal (arthrosis)
Shoulders 1 Sternoclavicular 3
17
6 Sternoclavicular joints. All non-specific synovitis. Immuno-fluorescent staining for rheumatoid factor negative in one instance
Shoulders 6. Acromiodavicular 15. Sternoclavicular 32. Wrists 10. Fingers 5.
WCC 4300, 3400, 4200. Poor mucin clot
6
Transient joint swelling and apparent inflammatory fluid in presence of ostcoarthrosis 1. Biopsy in all patients; 2. Knee biopsy consistent with RA in one patient Review article denying that synovitis occurs—synovitis excluded by definition Transient joint swelling only. Nonrecurrent. Autopsies in 6 patients without clinical arthritis showed no synovitis
Peripheral joints normal 11/27 patients sacroileitis Osteoarthrosis only
Transient effusions
Osteoarthrosis
Small transient effusions (not regarded by authors as synovitis)
Erosion-sclerosis of public symphysis 9. Sacroiliac 8. Erosions acromioclavicular 3. Sternoclavicular 5. MCP/PIP 3. Wrists 2
An unusually high frequency of joint involvement mainly based on joint swellings and tenderness. Biopsies in 5.
Normal
Mainly knees. Joint swelling. Always transient. No deformity
Fingers 6 Wrists 13 Cell count 1000-8000. 3% RA cells in 1 patient. Calcium pyrophosphate crystals in one
Comments
1 Synovitis
Selected cases. Cranial arteritis present in 3 patients with synovitis. Well documented synovitis in 3 with inflammatory fluid in 3 patients + biopsy in one (RA subsequently diagnosed in one other patient with synovitis)
0 2(6-5%)
2
Shoulder 1
Turbid, low viicoiity
Synovial rupture into the calf occurred No recurrence after steroid therapy Includes 2 patients with acute seronegative arthritis of the elderly.
13 (15%)
* Includes scleroderma 1, systemic lupus 1, rheumatoid urthritii 1.
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ACKNOWLEDGMENTS
We thank Dr. J. A. Cosh and Dr. R. Grahame for allowing us to examine their patients. REFERENCES ANDREWS, F. M. (1965) "Polymyalgia Rheumatica". Ann. rheum. Dis. 24,432. BAGRATUNI, L. (1963) "Prognosis in the Anarthritic Rheumatoid Syndrome". Br. med. J. 1, 513. BELL, W. R. and KLINEFELTER, N. F. (1967) "Polymyalgia rheumatica". Johns Hopkins med.
J. 121, 175. BRUK, M. I. (1967) "Articular and Vascular Manifestations of Polymyalgia Rheumatica". Ann. rheum. Dis. 26, 103. DAVIDSON, S., SPIERA, H. and PLOTZ, C. M. (1968) "Polymyalgia Rheumatica. Arthritis Rheum. 9,18. DIXON, A. ST. J. (1970) British Medical Association Annual Clinical Meeting Report. Br. med. J. 4,229.
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but may be self-limiting as transient joint swelling in the absence of treatment has been described (Bagratuni, 1963). Acute synovial rupture of the knee occurred in one of our patients and has been reported previously (Dixon et al., 1966). However, joint deformity, tendon nodules and tendon rupture were not seen and have not been described. Radiological erosion of peripheral joints was reported only in Bruk's (1967) series (13 instances among 80 patients using permissive criteria). Erosion and sclerosis of the sacroiliac joints and the symphysis pubis do occur (Andrews, 1965) and were present in Patient 2 and in one of our reference series of patients. At arthroscopy, the appearances of the synovium were those of inflammatory synovitis similar to the findings in rheumatoid arthritis. Changes in the surface articular cartilage were also seen but did not differ from the surface changes of degenerative joint disease normally present in patients of this age. Histology of the synovium showed synovial cell hyperplasia, an infiltrate of mixed inflammatory cells in the superficial subsynovium and hyperaemia. Although some features such as the fibrillary nature of the synovial cells, the superficial nature of the subsynovial infiltrate and little or absent iron deposition were noted, the changes were indistinguishable from those compatible with rheumatoid arthritis. This is not surprising as most features of rheumatoid arthritis are not specific and are shared by a variety of noninfective inflammatory arthritides. Attempts to stain the synovial membrane from patients with polymyalgia rheumatica for rheumatoid factor have not been successful (Andrews, 1965; Bruk, 1967). Like temporal arteritis associated with PMR, synovitis may occur many months after the onset of the disease at a time when the disease is apparently controlled by corticosteroid therapy or when the dosage is being reduced. It may be accompanied by a return of systemic symptoms. Both temporal arteritis and synovitis may occur in the same patient, sometimes simultaneously. Patients with PMR do occasionally develop typical RA but no more frequently than would be expected by chance in this age group (1 in 88 of the present series). Similarly rheumatoid factor is not found more frequently in patients with PMR than in the population and the presence of synovitis is not associated with seropositivity. There are other differences between PMR and rheumatoid arthritis, notably that in PMR the severity of the systemic illness, stiffness and disability outweigh the clinical evidence of joint involvement. Moreover, the joint involvement is transient, confined to a few joints and is not destructive. The sacroiliac joints and symphysis pubis may be affected in PMR but this is very uncommon in RA. Therefore there are good grounds for distinguishing this syndrome of PMR and synovitis from rheumatoid arthritis.
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BEARDWELL, C , KAY, A., WANKA, J. and WONG, Y. T. (1966) "Polymyalgia Rheumatica and Temporal Arteritis". Ann. rheum. Dis. 25,203. FORESTTER, J. and CERTONCINI, A. (1953) "Pseudopolyarthrite rhizomelique". Rev. Rhum. 20, 854. GORDON, I. (1960) "Polymyalgia Rheumatica, a Clinical Study of 21 Cases". Q. J. Med. 24,473. RENNIE, A. M. and BRANWOOD, A. W. (1964) "Polymyalgia Rheumatica, Biopsy Studies". Ann. rheum. Dis. 23, 447. HENDERSON, D. R. F., JAYSON, M. I. V. and TRIBE, C. R. (1975) "Lack of Correlation of Synovial Histology with Joint Damage in Rheumatoid Arthritis". Ann. rheum. Dis. 34,7-11. HUNDER, G. G., DISNEY, T. F. and WARD, I. E. (1969) "Polymyalgia Rheumatica". Proc. Mayo Clinic 44, 849. KAISER, H. (1969) "Polymyalgia Rheumatica". Munchener, med. Woch. 32, 1609. KERSLEY, G. D. (1956) "Anarthritic Rheumatoid Disease". Letter to the editor. Lancet ii, 840. KoGSTAD, O. A. (1965) "Polymyalgia Rheumatica and its Relation to Temporal Arteritis". Acta med. scand. 178, 591. DE SEZE, S., LEQUESNE, M. and VEBER, A. (1965). "La rheumatisme inflammatoire des ceintures ou Pseudo-polyarthrite Rhizomelique (Polymyalgia Rheumatica avec 45 observations)". Sem. hop. (Paris) 41, 711. WILSKE, K. R. and HEALY, L. A. (1967) "Polymyalgia Rheumatica. A Manifestation of Systemic Giant Cell Arteritis." Ann. int. Med. 66,77.
ORIGINAL PAPER
SYNOVITIS IN POLYMYALGIA RHEUMATICA BY D. R. F. HENDERSON*, C. R. TRIBE AND A. ST. J. DIXON Guy's Hospital, London; Department of Pathology, Southmead Hospital, Bristol; and Royal National Hospital for Rheumatic Diseases, Bath
SYNOVITIS is infrequent in polymyalgia rheumatica (PMR). It is often the absence of joint involvement in patients with proximal limb-girdle stiffness, constitutional illness and a rapid erythrocyte sedimentation rate (e.s.r.) that suggests this diagnosis. However, it does occasionally occur, for example, in four out of sixty-five patients reported by Dixon (1970). Non-specific synovitis has also been described in biopsy studies from the shoulder and sternoclavicular joints of three series of patients (Gordon, Rennie and Branwood, 1964; Andrews, 1965; and Bruk, 1967). We describe arthroscopy, synovial fluid analysis and biopsy observations in four patients with PMR and synovitis of the knee. One also had sacroiliac joint changes and one further patient had involvement of the wrist and shoulder. These findings have been related to a series of 88 consecutive patients with PMR (with and without temporal arteritis) seen and treated in Bath during 1965 and 1973. The criteria for the diagnosis of PMR (Dixon et al., 1966) required, first, the presence of intense stiffness of proximal limb movements especially after resting, a raised e.s.r. (Westergren) and a rapid response to corticosteroids; and, second, the absence of rheumatoid arthritis, systemic lupus erythematosis, polymyositis, carcinomatosis or other disease which might present in a similar manner. These were excluded by consistently negative results in a battery of appropriate screening tests, muscle biopsy and radiography which will not be further detailed, apart from those relevant to synovitis. As evidence of synovitis we have accepted swelling of the joints or tendon sheaths containing fluid with an increased number of white cells, or synovial biopsy showing inflammation. Stiff, limited or painful joint movement and small effusions of clear fluid were not accepted as indicative of synovitis.
PATIENTS PATIENT 1
Mrs. A. A. at the age of 67 rapidly developed pain in the shoulder muscles, buttocks and thighs which prevented walking. Morning stiffness and malaise were present. The * Present address: The Queen Elizabeth Hospital, Woodville, South Australia 5011. Accepted for publication December 1974. 244
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SUMMARY Synovitis was observed in 13 out of 88 consecutive patients with polymyalgia rheumatica. It is described in detail in five patients, on the basis of clinical and radiological observations, joint aspiration, arthroscopy and biopsy. The synovitis of polymyalgia rheumatica cannot be distinguished histologically or at arthroscopy from the appearance seen in mild rheumatoid arthritis. Clinically, however, the synovitis of polymyalgia rheumatica is mild, transient and confined to one or two joints or tendon sheaths. It is not followed by joint deformity or by radiological erosive changes in the bone ends. It may occur at any stage of the disease but particularly at its onset, or when the dose of corticosteroid treatment is reduced.
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PATIENT 2
Mrs. N. W. at the age of 54 developed pain and stiffness in the shoulders, neck and arms following surgery for bilateral hallux valgus. The e.s.r. was 53 mm/h. Prednisolone 15 mg/day improved the symptoms. The dose was reduced over the next two years. Age 60, she again developed fever and limb stiffness with painful swelling of the knees with a popliteal cyst. Prednisolone 7.5 mg was given and she was admitted to hospital. Hb 11.5 g/dl; e.s.r. 120 mm/h; serum proteins 8 g/dl (Alb. 3.2, Glob. 4.8) with a diffuse increase in the y-globulin. The Rose test was negative in all but one of many estimations. Radiography showed erosion of the symphysis pubis. Inflammatory synovial fluid was removed from one knee. The patient improved with rest and prednisolone in the same dosage but symptoms returned after discharge. Age 61 she was readmitted with synovitis of the right knee and stiffness of shoulder movement without swelling; Hb 10.4 g/dl; e.s.r. 100 mm/h; Antinuclear factor absent. The histocompatability antigen HLA W 27 was absent. Radiography showed increase in the sclerotic changes in the symphysis pubis and erosion and sclerosis of the left sacroiliac joint. Attempts to reduce the daily dose of prednisolone below 15 mg resulted in a return of the symptoms and raised e.s.r. At age 62, arthroscopy of the knee confirmed synovitis.
PATIENT 3
Mrs. M.S., an art dealer aged 68, developed PMR without joint swelling which responded to prednisolone 12.5 mg/day. The dose was gradually reduced to 3 mg/day with regular supervision and control. At age 70, having been active, vigorous and regularly at work, she relapsed, with pain and swelling of the right knee from which inflammatory joint fluid was withdrawn. Synovitis responded temporarily to an injection of hydrocortisone acetate (40 mg). One month later she had a typical episode of temporal arteritis associated with temporal scalp pain, tenderness over the temporal arteries and headache. Arthroscopy of the right knee revealed erythema and swollen polypoid villi. Some fibrin was present. The cartilage showed only mild degenerative changes.
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joints were normal. She appeared myxoedematous. Investigations: Hb 10.0 g/dl; e.s.r. 103 mm/h; Rose test for rheumatoid factor negative on five occasions; albumin 3.9 g/dl; globulin 3.2 g/dl, alpha-2 globulins increased; protein-bound iodine 0.5 /*g/dl; cholesterol 340 g/dl. Thyroxine 0.1 g/day corrected her hypothyroidism which caused no further concern. Prednisolone 15 mg/day controlled her PMR and the e.s.r. fell to 10 mm/h. The dose was progressively reduced but at eighteen months at 2.5 mg/day symptoms recurred, followed after two months by an effusion in the left knee complicated in turn by popliteal swelling and acute synovial rupture. Her condition responded to rest and methylprednisolone 16 mg/day. Three months later, again following reduction of the dose, pain and stiffness returned, both knees swelled and the e.s.r. rose to 83 mm/h. Synovial fluid aspirated from the knee was turbid, of low viscosity and contained 85% polymorphs and 15% lymphocytes. The synovial Rose test was weakly positive. At arthroscopy the synovium showed erythema, oedema and polyp formation. The articular surface showed mild degenerative changes. Under continued observation, the knees became normal. No other joints have been affected and radiographs have shown only mild arthrosis.
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RHEUMATOLOGY AND REHABILITATION VOL. XIV NO. 4 PATIENT 4
PATIENT 5
Mr. G.H-F., aged 76, noted the rapid onset of generalized stiffness particularly affecting the shoulders, buttocks and thighs. From being remarkably active for his age he found himself neither able to dress unaided nor to rise unassisted from an easy-chair. A small swelling in the right subdeltoid bursa was aspirated producing slightly turbid inflammatory fluid. Inflammatory swelling of the right common extensor tendon sheath at the wrist was also present. There was a mild anaemia (Hb 10.8 g/dl) a raised e.s.r. (50 mm/h) and a negative test for rheumatoid factor. All other investigations were negative. The evidence of synovitis disappeared under treatment with 5 mg/day of prednisolone and this dose was steadily reduced and finally withdrawn after two years. At followup aged 80, he remained well and has regained his previous vigour, off all treatment and without evidence of synovitis. REFERENCE SERIES A reference series of 88 patients with PMR seen in Bath in the years 1965 to 1971 (part of a series previously described to a meeting of the British Medical Association, Dixon, 1970) included 21 patients with a strong clinical evidence of giant cell arteritis confirmed by positive biopsy in six, cranial arteriogram in one or the prior development of sudden blindness in two. Of these 88 patients, 70 showed no evidence of joint disease at any time. Five further patients had osteoarthrosis affecting the knees without inflammatory changes, diagnosed on clinical grounds and confirmed in all by aspiration of a small amount of water-clear, viscid joint fluid. Thus, only 13 out of 88 showed any evidence of inflammatory synovitis. In nine, the knee showed synovitis confirmed in four by aspiration of turbid fluid of a low viscosity (and incidently negative for rheumatoid factor in three out of three tested) and, in six, there was a generalized oedema of the hands to which synovitis of the wrist and finger joints appeared to be contributing (four of these also had synovitis of the knee at the same time). One patient who had previously had a positive temporal artery biopsy subsequently went on to develop classical seropositive rheumatoid arthritis; the only one to do so in this series (this could be expected from the
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Mr. E.S., a shopkeeper aged 60, noted the rapid onset of pain and immobilizing stiffness in the shoulders, buttocks and thighs. Shoulders, elbows, knee and wrists were limited in range of movement. No joint was swollen. The Hb was 12 g/dl; the e.s.r. was 87 mm/h; rheumatoid factor was absent. He was treated with prednisolone 10 mg daily with immediate improvement and the e.s.r. fell to 18 mm/h. Prednisolone was reduced gradually to 5 mg daily and maintained at from 5 to 7 mg a day until aged 63 when dose reduction was again attempted. At 3 mg/day, he noted fatigue accompanied by painful swelling and stiffness of the knees, The left ankle was warm with some swelling. Hb 11.8 g/dl; e.s.r. 79 mm/h; the WCC 9000/mm3, rheumatoid factor absent. Arthroscopy of the right knee disclosed inflammatory synovial fluid and synovium with mild degenerative changes in the articular cartilage. Prednisolone was increased to 5 mg/day with improvement and the e.s.r. fell from 80 to 41 mm/h. When followed up four years after the onset of his illness and six months after the esisode of synovitis he remained well and was clinically normal.
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prevalence of rheumatoid arthritis in the population). One patient (patient 5 in this report) developed transient synovitis with effusions of the shoulder and extensor tendon sheath and one developed symptomless radiological evidence of nonankylosing sacroiliac arthritis (Andrews, 1965) similar to that seen in Patient 2.
DISCUSSION The frequency of joint involvement in reported series of patients with PMR is shown in the Table and ranges from none to two thirds. The lowest frequency comes from authors who consider that the presence of synovitis precludes the diagnosis of PMR, e.g. Forestier and Certoncini, 1963; Davidson, Spiera and Plotz, 1966. The larger figures come from a series (Bruk, 1967) in which the criteria for admission included central joint tenderness and the criteria for synovitis included palpable synovial thickening or demonstrable synovial effusion. These criteria may have been too permissive (small effusions are common in the knees of normal elderly people). However, there are a number of acceptable reports of synovitis supported in some instances by synovial biopsy or synovial fluid analysis. Taking into account differences in methodology, the frequency lies between 15 and 50%. The joints most frequently affected are the knees, wrist,fingersand shoulders, in that order. The arthritis is transient, lasting days or weeks and appears to respond well to local or systemic corticosteroid therapy,
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HISTOLOGICAL STUDIES Synovial biopsies obtained under direct vision at arthroscopy from the knee-joints of Patients 1-4 were examined. In order not to bias the interpretations, the synovial biopsy specimens were examined "blind" amongst other synovial biopsy specimens obtained at arthroscopy from 21 patients with proven rheumatoid arthritis (RA) which were being studied as part of an attempt to correlate biopsy appearances with the course and progress of the patients' arthritis (Henderson, Jayson and Tribe, 1975). The histclogical appearances varied widely among these patients with RA and no relation could be found between a range of histological features on the one hand and the clinical, radiological and arthroscopicfindingson the other. Furthermore, all the histological features of the synovium in our patients with PMR synovitis could be accommodated within this wide range of appearances in these patients with RA. These changes were essentially similar in all four instances and consisted of synovial tissue hyperplasia, hyperaemia and a moderate mixed cellular infiltrate of lymphocytes and plasma cells in the subsynovium. The synovial hyperplasia varied in thickness from three to five cells wide and in all the biopsies had a loosefibrillaryoedematous appearance with wide separation of the nuclei. The degree of cellular infiltration of the subsynovium varied considerably in different areas of the biopsies. It tended to be superficial and the number of plasma cells and lymphocytes was usually about equal. In only one biopsy was there any attempt at lymph follicle formation. In all biopsies, the stroma contained many small vessels. Certain histological features did seem to be more common in PMR than in RA. These were: 1. The synovial lining hyperplasia was always three cells wide or more and often had a peculiar oedematous fibrillary appearance. 2. The stromal infiltrate tended to be superficial and was composed of equal numbers of plasma cells and lymphocytes. 3. Iron deposition was very mild and small amounts only were found in 1 out of 4 of these patients as compared with 10 out of 21 patients with rheumatoid arthritis who had mild to severe iron deposition.
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TABLE: COMPARISON OF THB FREQUENCY OF JOINT INVOLVEMENT AND SYNOVITIS FOUND IN PATIENTS WITH POLYMYALOIA RHEUMATICA
Author
Year No. of No. with Knees patients synovitis
Kersley
1956
13
3 (23%)
Gordon
I960
21
6 (29%)
Gordon el al.
1964
6
Forestier and Certoncini
1953
Bagratini
1963
50
Andrews
1965
37
Kogstad
1965
70
de Seze el al.
1965
45
Wilske and Healy
1967
18
8 (44%)
8
Bruk
1967
80
55 (69%)
40
Bell and Klinefelter Handa el al.
1967
29
11(38%)
1969
12«
6(50%)
Kaiser
1969
5
Dixon el al.
1966
31
Present series
4
6 (100%)
Other joints
Tapped
MCP 1 PIP1
1
Fluid
Biopsy
Radiography
Many polymorphs. Few Mononudear cells 6 Capsule biopsies show nospecific inflammation
Shoulders
0
88
8 (16%)
1 Normal
Sacroiliac symphysis pubis 11 (16%)
7 Stemodavicular 6 Abnormal (arthrosis)
Shoulders 1 Sternoclavicular 3
17
6 Sternoclavicular joints. All non-specific synovitis. Immuno-fluorescent staining for rheumatoid factor negative in one instance
Shoulders 6. Acromiodavicular 15. Sternoclavicular 32. Wrists 10. Fingers 5.
WCC 4300, 3400, 4200. Poor mucin clot
6
Transient joint swelling and apparent inflammatory fluid in presence of ostcoarthrosis 1. Biopsy in all patients; 2. Knee biopsy consistent with RA in one patient Review article denying that synovitis occurs—synovitis excluded by definition Transient joint swelling only. Nonrecurrent. Autopsies in 6 patients without clinical arthritis showed no synovitis
Peripheral joints normal 11/27 patients sacroileitis Osteoarthrosis only
Transient effusions
Osteoarthrosis
Small transient effusions (not regarded by authors as synovitis)
Erosion-sclerosis of public symphysis 9. Sacroiliac 8. Erosions acromioclavicular 3. Sternoclavicular 5. MCP/PIP 3. Wrists 2
An unusually high frequency of joint involvement mainly based on joint swellings and tenderness. Biopsies in 5.
Normal
Mainly knees. Joint swelling. Always transient. No deformity
Fingers 6 Wrists 13 Cell count 1000-8000. 3% RA cells in 1 patient. Calcium pyrophosphate crystals in one
Comments
1 Synovitis
Selected cases. Cranial arteritis present in 3 patients with synovitis. Well documented synovitis in 3 with inflammatory fluid in 3 patients + biopsy in one (RA subsequently diagnosed in one other patient with synovitis)
0 2(6-5%)
2
Shoulder 1
Turbid, low viicoiity
Synovial rupture into the calf occurred No recurrence after steroid therapy Includes 2 patients with acute seronegative arthritis of the elderly.
13 (15%)
* Includes scleroderma 1, systemic lupus 1, rheumatoid urthritii 1.
HENDERSON ET AL.: SYNOVITIS IN POLYMYALGIA RHEUMATICA
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ACKNOWLEDGMENTS
We thank Dr. J. A. Cosh and Dr. R. Grahame for allowing us to examine their patients. REFERENCES ANDREWS, F. M. (1965) "Polymyalgia Rheumatica". Ann. rheum. Dis. 24,432. BAGRATUNI, L. (1963) "Prognosis in the Anarthritic Rheumatoid Syndrome". Br. med. J. 1, 513. BELL, W. R. and KLINEFELTER, N. F. (1967) "Polymyalgia rheumatica". Johns Hopkins med.
J. 121, 175. BRUK, M. I. (1967) "Articular and Vascular Manifestations of Polymyalgia Rheumatica". Ann. rheum. Dis. 26, 103. DAVIDSON, S., SPIERA, H. and PLOTZ, C. M. (1968) "Polymyalgia Rheumatica. Arthritis Rheum. 9,18. DIXON, A. ST. J. (1970) British Medical Association Annual Clinical Meeting Report. Br. med. J. 4,229.
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but may be self-limiting as transient joint swelling in the absence of treatment has been described (Bagratuni, 1963). Acute synovial rupture of the knee occurred in one of our patients and has been reported previously (Dixon et al., 1966). However, joint deformity, tendon nodules and tendon rupture were not seen and have not been described. Radiological erosion of peripheral joints was reported only in Bruk's (1967) series (13 instances among 80 patients using permissive criteria). Erosion and sclerosis of the sacroiliac joints and the symphysis pubis do occur (Andrews, 1965) and were present in Patient 2 and in one of our reference series of patients. At arthroscopy, the appearances of the synovium were those of inflammatory synovitis similar to the findings in rheumatoid arthritis. Changes in the surface articular cartilage were also seen but did not differ from the surface changes of degenerative joint disease normally present in patients of this age. Histology of the synovium showed synovial cell hyperplasia, an infiltrate of mixed inflammatory cells in the superficial subsynovium and hyperaemia. Although some features such as the fibrillary nature of the synovial cells, the superficial nature of the subsynovial infiltrate and little or absent iron deposition were noted, the changes were indistinguishable from those compatible with rheumatoid arthritis. This is not surprising as most features of rheumatoid arthritis are not specific and are shared by a variety of noninfective inflammatory arthritides. Attempts to stain the synovial membrane from patients with polymyalgia rheumatica for rheumatoid factor have not been successful (Andrews, 1965; Bruk, 1967). Like temporal arteritis associated with PMR, synovitis may occur many months after the onset of the disease at a time when the disease is apparently controlled by corticosteroid therapy or when the dosage is being reduced. It may be accompanied by a return of systemic symptoms. Both temporal arteritis and synovitis may occur in the same patient, sometimes simultaneously. Patients with PMR do occasionally develop typical RA but no more frequently than would be expected by chance in this age group (1 in 88 of the present series). Similarly rheumatoid factor is not found more frequently in patients with PMR than in the population and the presence of synovitis is not associated with seropositivity. There are other differences between PMR and rheumatoid arthritis, notably that in PMR the severity of the systemic illness, stiffness and disability outweigh the clinical evidence of joint involvement. Moreover, the joint involvement is transient, confined to a few joints and is not destructive. The sacroiliac joints and symphysis pubis may be affected in PMR but this is very uncommon in RA. Therefore there are good grounds for distinguishing this syndrome of PMR and synovitis from rheumatoid arthritis.
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BEARDWELL, C , KAY, A., WANKA, J. and WONG, Y. T. (1966) "Polymyalgia Rheumatica and Temporal Arteritis". Ann. rheum. Dis. 25,203. FORESTTER, J. and CERTONCINI, A. (1953) "Pseudopolyarthrite rhizomelique". Rev. Rhum. 20, 854. GORDON, I. (1960) "Polymyalgia Rheumatica, a Clinical Study of 21 Cases". Q. J. Med. 24,473. RENNIE, A. M. and BRANWOOD, A. W. (1964) "Polymyalgia Rheumatica, Biopsy Studies". Ann. rheum. Dis. 23, 447. HENDERSON, D. R. F., JAYSON, M. I. V. and TRIBE, C. R. (1975) "Lack of Correlation of Synovial Histology with Joint Damage in Rheumatoid Arthritis". Ann. rheum. Dis. 34,7-11. HUNDER, G. G., DISNEY, T. F. and WARD, I. E. (1969) "Polymyalgia Rheumatica". Proc. Mayo Clinic 44, 849. KAISER, H. (1969) "Polymyalgia Rheumatica". Munchener, med. Woch. 32, 1609. KERSLEY, G. D. (1956) "Anarthritic Rheumatoid Disease". Letter to the editor. Lancet ii, 840. KoGSTAD, O. A. (1965) "Polymyalgia Rheumatica and its Relation to Temporal Arteritis". Acta med. scand. 178, 591. DE SEZE, S., LEQUESNE, M. and VEBER, A. (1965). "La rheumatisme inflammatoire des ceintures ou Pseudo-polyarthrite Rhizomelique (Polymyalgia Rheumatica avec 45 observations)". Sem. hop. (Paris) 41, 711. WILSKE, K. R. and HEALY, L. A. (1967) "Polymyalgia Rheumatica. A Manifestation of Systemic Giant Cell Arteritis." Ann. int. Med. 66,77.
