1060 Ann Rheum Dis 2001;60:1060–1063 Ann Rheum Dis: first published as 10.1136/ard.60.11.1060 on 1 November 2001. Downloaded from Musculoskeletal manifestations in polymyalgia rheumatica and temporal

J Narváez, J M Nolla-Solé, J A Narváez, M T Clavaguera, J Valverde-García, D Roig-Escofet

Abstract erythrocyte sedimentation rate. The cause of Objective—To evaluate the incidence and musculoskeletal pain in PMR is not completely characteristics of musculoskeletal mani- understood, but inflammation in proximal festations in polymyalgia rheumatica joints and periarticular structures is a likely (PMR) and temporal arteritis (TA). basis for much of the discomfort since, to date, Methods—The records of 163 cases of there is little evidence to suggest that the PMR or TA diagnosed over a 15 year musculoskeletal symptoms are related to under- period in one area of Spain were reviewed lying . Evidence of proximal articular for the presence and type of musculo- and periarticular has been demon- skeletal manifestations. strated by scanning, MRI, arthroscopy, and Results—Of 163 patients, 90 had isolated synovial biopsy.1–3 Moreover, an increasing PMR and 73 had TA. Eighteen of the 90 number of reports have underlined the presence patients (20%) with isolated PMR devel- of peripheral synovitis and other distal muscu- oped distal peripheral arthritis either at loskeletal manifestations in PMR, suggesting diagnosis or during the course of the that the spectrum of musculoskeletal involve- disease. When it occurred, synovitis was ment in this entity is not completely defined and mild, monoarticular or pauci-articular, is broader than has often been thought asymmetrical, transient, and not destruc- previously.4–8 The clinical predominance of tive. Other distal manifestations observed proximal symptoms in PMR has probably over- in these patients were carpal tunnel shadowed the less well characterised and more syndrome and distal extremity swelling variable distal musculoskeletal manifestations.4 with pitting oedema. In all cases these TA is a vasculitis of large and medium sized manifestations occurred in conjunction vessels with a predisposition to the cranial with active PMR. As expected, PMR was arteries in patients older than 50 years. the most frequent musculoskeletal mani- Although cranial and ocular symptoms are the Department of festation in patients with TA, occurring in most prominent manifestations in TA, , 56% of cases. On the contrary, only 11% of musculoskeletal findings, especially those of Hospital Príncipes de patients with TA developed peripheral PMR, are also common. However, controversy España, Ciudad arthritis. An important finding was that exists over the presence of distal musculoskel- http://ard.bmj.com/ Sanitaria y etal manifestations in TA and two recent stud- Universitaria de peripheral arthritis in these patients ap- Bellvitge, Barcelona, pears to be linked only temporally to the ies have produced conflicting results. Salvarini Spain presence of simultaneous PMR and is not et al, in a population based study at the Mayo J Narváez observed in its absence. Distal extremity Clinic, reported common and varied distal J M Nolla-Solé swelling or defined polyarthritis were not musculoskeletal symptoms in TA which sug- M T Clavaguera observed. gested that the nature of this condition and its J Valverde-García Conclusion—The spectrum of distal mus- clinical expression are broader than has often

D Roig-Escofet on September 26, 2021 by guest. Protected copyright. culoskeletal manifestations of PMR in our been considered, and supporting the link 9 Department of CT and series is similar to that reported in other between TA and PMR. By contrast, Gran et al, MRI, Institut de populations. By contrast, distal musculo- in a recent prospective study conducted in Diagnòstic per la skeletal symptoms are uncommon in TA. Norway, noted the particular absence of Imatge, Hospital The almost complete absence of distal peripheral arthritis in this group of patients.10 Duran I Reynals, The occurrence of peripheral arthritis in PMR Ciudad Sanitaria y musculoskeletal manifestations in pa- Universitaria de tients with pure TA suggests diVerent and not in TA may reflect diVerent mecha- Bellvitge, Barcelona, mechanisms of disease in PMR and TA, nisms of disease. Spain supporting the view of two separate condi- In view of these contradictory observations, J A Narváez tions or one common disease in which we have reviewed the musculoskeletal manifes- host susceptibility influences the clinical tations in a well defined cohort of 163 patients Rheumatology Unit, with PMR and/or TA diagnosed over a 15 year Department of expression. Internal Medicine, (Ann Rheum Dis 2001;60:1060–1063) period in an eVort to provide an accurate clini- Delfos Medical Center, cal picture of the frequency and clinical Barcelona, Spain spectrum of these manifestations, and have J Narváez There is controversy as to whether polymyalgia compared our results with those reported in rheumatica (PMR) and temporal arteritis (TA) other major studies of this condition. Correspondence to: are expressions of the same disease or are two Dr F J Narváez Garcia, C/ Llobregat no 5, 3 1, diVerent, partly overlapping, diseases. PMR is Hospitalet de Llobregat, a common syndrome of the elderly character- Methods 08904 Barcelona, Spain ised by pain and stiVness involving the , We retrospectively analysed all patients with [email protected] and pelvic girdles, generally accompa- PMR and/or TA diagnosed from 1985 to 1999 Accepted 18 April 2001 nied by constitutional symptoms and a raised by the Department of Rheumatology of

www.annrheumdis.com Musculoskeletal manifestations in polymyalgia rheumatica and temporal arteritis 1061 Ann Rheum Dis: first published as 10.1136/ard.60.11.1060 on 1 November 2001. Downloaded from Table 1 Joints involved during 20 episodes of peripheral isolated PMR. The mean (SD) age at time of arthritis in 90 patients with isolated polymyalgia diagnosis for all patients was 72 (8) years rheumatica (PMR) and during eight episodes of peripheral arthritis in 73 patients with temporal arteritis (TA) (range 51–89) and the mean duration of symp- toms prior to the diagnosis was 2.7 (2.6) Joint Isolated PMR TA months. The main clinical features and labora- Knee 11 (55%) 4 (50%) tory data of most of these patients have been 13 Wrist 7 (35%) 4 (50%) extensively reported elsewhere. Metacarpophalangeal 5 (25%) 2 (25%) Proximal interphalangeal 3 (20%) – PATIENTS WITH ISOLATED PMR Elbow 1 (5%) 2 (25%) Sternoclavicular 2 (10%) 2 (25%) Eighteen of the 90 patients (20%) with pure Ankle – 1 (12.5%) PMR developed clinically detectable periph- eral synovitis in whom crystal arthritis and Data are presented as number (%) of episodes. osteoarthritis were excluded. Table 1 lists the Bellvitge Hospital, Barcelona, Spain. The diag- joints involved. These patients presented non- nosis of PMR was based on the criteria deforming monoarthritis or oligoarthritis in- proposed by Chuang et al.11 Patients were con- volving mainly wrists and knees or, less sidered to have PMR if they met these criteria frequently, the sternoclavicular joints, elbows, and had a rapid and persistent response to or some metacarpophalangeal (MCP) or proxi- treatment. The presence of other mal interphalangeal (PIP) joints. None of them diseases that might explain the symptoms such developed defined polyarthritis during the as chronic infection, connective tissue diseases, study. All of the patients presented with or malignancy excluded the diagnosis of PMR. peripheral manifestations at the time of diagno- The diagnosis of TA was made according to the sis and only two of the 18 had a second episode 1990 ACR criteria.12 Patients were diagnosed of peripheral symptoms when PMR relapsed. as having TA if they had a positive artery biopsy None of these patients presented with periph- specimen or, in cases with a negative biopsy or eral manifestations while proximal symptoms no biopsy, if they fulfilled the remaining four of PMR were absent. criteria and had a prompt and persistent Synovitis was transient and mild, usually response to corticosteroid treatment. asymmetrical, and resolved completely after After diagnosis all selected patients under- corticosteroid therapy was started or the pred- went periodic examinations at the outpatient nisone dose was increased. Rheumatoid factor clinic until death or cessation of treatment and was negative in all cases. No erosive changes or permanent disease remission. All patients were juxta-articular osteoporosis were seen on plain examined by a rheumatologist. radiographs of aVected joints. Two patients Inpatient and outpatient charts of all pa- (2%) with synovitis of the wrists referred tients were reviewed comprehensively to obtain symptoms of acute carpal tunnel syndrome. clinical, laboratory, and disease evolution data Finally, only one of the 18 patients (1%) devel- according to a specifically designed protocol. oped distal symmetrical swelling of the upper The end point of patient follow up was the date limbs with pitting oedema over the dorsum of of the last clinic visit or the date of death. In all the hands and wrists concurrently with proxi- http://ard.bmj.com/ selected patients we recorded information on mal PMR symptoms. In this patient MRI the presence and type of musculoskeletal examination showed severe extensor tenosyno- manifestations, their relationship to the onset vitis with peritendinous oedema, without and course of the disease, and their response to evidence of concomitant wrist or hand joint treatment. We have not included in the study synovitis. HLA B7 was negative. Corticoster- the presence of arthralgias since the high oids were given and the swelling responded frequency of degenerative disease in this elderly

promptly. No residual were ob- on September 26, 2021 by guest. Protected copyright. population would make its interpretation diY- served. cult. We have also excluded those patients with peripheral arthritis in whom, after examination of joint fluid and/or radiological study, the PATIENTS WITH TEMPORAL ARTERITIS symptoms could be related to crystal associ- Forty one of the 73 patients (56%) developed ated arthritis or severe osteoarthritis. PMR at some time during the course of their TA. As in patients with pure PMR, shoulder STATISTICAL ANALYSIS pain was the most frequent feature being A comparative study between patients with and observed in 100% of the patients, while the without musculoskeletal manifestations was hips and neck were less commonly aVected. performed using the Student’s t test for In 33 patients PMR began concurrently (<1 independent continuous variables or the month from the diagnosis of TA), in one PMR Mann-Whitney U test when the assumption of began at some time after TA was diagnosed as normality was not realised. To analyse categori- a result of one relapse, and in seven patients cal data we performed the ÷2 test or the Fisher’s PMR began before TA. These seven patients exact test when the expected values were less were originally diagnosed as having isolated than 5. Statistical significance was defined as PMR because none presented with clinical evi- p<0.05. dence of TA (in none of them was a temporal artery biopsy specimen taken at the time of Results diagnosis). One suVered an arteritic recurrence From 1985 to 1999 inclusive a total of 163 26 months after the end of a 29 month course patients (107 women) were diagnosed with TA of treatment. The remaining six experienced an and/or PMR. Of these, 73 had TA and 90 had arteritic relapse during the course of steroid

www.annrheumdis.com 1062 Narváez, Nolla-Solé, Narváez, et al Ann Rheum Dis: first published as 10.1136/ard.60.11.1060 on 1 November 2001. Downloaded from Table 2 Comparison between patients with and without distal musculoskeletal manifestations

Patients with distal Patients without distal musculoskeletal manifestations musculoskeletal manifestations (A) Patients with isolated PMR n=18 (20%) n=72 (80%) p Value Mean (SD) age at onset of disease (years) 71.3 (9) 71.8 (8) NS F:M ratio 12/6 (2) 46/26 (1.8) NS Malaise/anorexia/weight loss 9 (50%) 40 (55%) NS Low grade fever 1 (6%) 6 (8%) NS Mean (SD) ESR (mm/h) 72 (23) 74 (20) NS Mean (SD) haemoglobin (g/l) 116 (13) 118 (12) NS Raised alkaline phosphatase 4 (22%) 12 (17%) NS Raised ALT/AST 2 (11%) 6 (8%) NS

Patients without Patients with musculoskeletal musculoskeletal manifestations (B) Patients with TA manifestations n=41 (56%) n=32 (44%) p Value Mean (SD) age at onset of disease (years) 71.4 (8) 73 (9) NS F:M ratio 28/13 (2.1) 21/11 (1.9) NS 41 (100%) 32 (100%) NS Abnormal temporal artery 35 (85%) 29 (90%) NS Jaw claudication 17 (41%) 8 (25%) NS Malaise/anorexia/weight loss 27 (66%) 19 (59%) NS Fever 7 (17%) 2 (6%) NS Amaurosis fugax 10 (24%) 4 (12%) NS Mean (SD) ESR (mm/h) 91 (24) 80 (21) NS Mean (SD) haemoglobin (g/l) 110 (13) 115 (14) NS Raised alkaline phosphatase 10 (24%) 7 (22%) NS Raised ALT/AST 5 (12%) 3 (9%) NS

PMR = polymyalgia rheumatica; TA = temporal arteritis; ESR = erythrocyte sedimentation rate; ALT/AST = alanine aminotransferase/aspartate aminotransferase; SD = standard deviation.

treatment (median time to relapse from initia- sedimentation rate, lower values of haemo- tion of therapy 26 (16) weeks). Relapses globin, and an increased incidence of constitu- usually occurred during the tapering of the tional symptoms, jaw claudication, and visual dose or as a consequence of an problems, although these diVerences were no unauthorised discontinuation of treatment longer statistically significant (table 2). (n=1). In these seven cases arteritis was confirmed by a positive biopsy specimen. Discussion Eight of the 73 patients with TA (11%) There is considerable controversy regarding developed clinically detectable synovitis. Inter- the frequency of peripheral synovitis in PMR estingly, all of these patients also had PMR. since its reported incidence varies consider- Table 1 lists the joints involved. In six a ably, ranging from 6% to 60% in various non-deforming, self-limited mono or asym- series.4–7 These discrepancies may be attributed

metrical oligoarthritis was observed, aVecting to the variable use of diVerent diagnostic crite- http://ard.bmj.com/ mainly knees and wrists or, less frequently, ria for PMR (with important selection bias in elbows or some MCP or PIP joints. The the ascertainment of PMR cases), the defini- remaining two patients presented with tender- tion of synovitis (which has been equated with ness and mild swelling of both sternoclavicular arthralgia in some studies), and diYculty in the joints. No erosive changes were seen on plain interpretation of scans and radiographs due to radiographs of the aVected joints, although coexisting degenerative disease. In our series, erosions in the sternoclavicular joints were 20% of patients with isolated PMR developed confirmed by tomography in two patients. All clinically detectable peripheral arthritis either on September 26, 2021 by guest. Protected copyright. of the eight patients developed peripheral at diagnosis or during the course of the disease. manifestations concurrently with the time This percentage is very similar to those 457 proximal PMR began. In all cases synovitis was reported in previous observations. In all of transient and this manifestation resolved com- these cases peripheral synovitis occurred in pletely after corticosteroid treatment was conjunction with active PMR, particularly at its started. Clinical symptoms suggesting carpal onset or, less frequently, during a relapse. The tunnel syndrome were observed in one patient data suggest that synovitis is not uncommon in (1%) with synovitis of the wrists. Distal PMR, and seems to be a main contributing extremity swelling, , or defined factor to many of the symptoms seen in polyarthritis were not observed in any patient. patients with this condition. When it occurred, synovitis presented as mono or asymmetrical oligoarthritis involving mainly wrists and COMPARISONS BETWEEN PATIENTS WITH AND knees. Unlike rheumatoid arthritis, synovitis WITHOUT MUSCULOSKELETAL MANIFESTATIONS was transient and mild, non-deforming, and At the time of diagnosis patients with PMR and resolved completely after corticosteroid treat- distal musculoskeletal manifestations did not ment was started or the prednisone dose was diVer from those without these features. In increased. None of the patients developed comparing patients with TA and musculoskel- defined polyarthritis. Rheumatoid factor was etal symptoms with those without, we observed negative in all cases. No erosive changes or that the group with musculoskeletal findings juxta-articular osteoporosis were seen on plain seemed to have more severe disease character- radiographs of aVected joints. Although it has ised by a greater increase in erythrocyte been suggested that the presence of peripheral

www.annrheumdis.com Musculoskeletal manifestations in polymyalgia rheumatica and temporal arteritis 1063 Ann Rheum Dis: first published as 10.1136/ard.60.11.1060 on 1 November 2001. Downloaded from arthritis in PMR is associated with a longer important finding was that peripheral joint duration of steroid treatment and a higher fre- involvement was only present in conjunction quency of relapses indicating a subset with with active PMR and was not observed when more severe disease,5 in our series patients with PMR was absent. The particular absence of PMR and distal musculoskeletal manifesta- peripheral arthritis in patients with isolated TA tions did not diVer from those without them. has also been observed previously by several Other distal manifestations observed in authors10 and may, to some extent, indicate patients with isolated PMR were carpal tunnel important diVerences in the aetiopathogenesis syndrome and distal extremity swelling with of PMR and TA. Moreover, distal extremity pitting oedema. The incidence of carpal tunnel swelling with pitting oedema was not observed syndrome described in previous reports ranges in any case and, contrary to other reports that from 6% to 14%, being mainly attributed to have described both seronegative and seroposi- wrist flexor tenosynovitis.4–6 11 In our popula- tive rheumatoid arthritis in patients with tion this percentage was substantially lower TA, 91415 none of our patients developed (2%) and in these patients carpal tunnel defined polyarthritis during the study. syndrome resulted mainly from synovitis of the In summary, although the frequency of distal wrists. Distal extremity swelling with pitting musculoskeletal manifestations observed in oedema represents another clinical feature our patients with PMR was diVerent from that recently recognised in PMR; in our series only given in some previous reports, overall the 1% of patients with isolated PMR had distal findings of this study support and confirm the swelling with pitting oedema compared with an similar findings found in diVerent populations incidence of 8–12% in earlier reports.458 We with this condition. However, in contradiction cannot completely explain the low incidence of to another major study of this condition,9 we distal extremity swelling in our patients. A ret- found that distal musculoskeletal manifesta- rospective review such as this is inevitably tions in patients with TA were uncommon. associated with a bias toward underreporting of Peripheral synovitis in these patients appears to these features. In this regard, it is reasonable to be linked only temporally to the presence of assume that some manifestations, especially simultaneous PMR. The almost complete those less recognisable or unfamiliar, may have absence of peripheral arthritis and other distal been overlooked. However, the patients were musculoskeletal manifestations in patients with carefully evaluated at regular intervals and, pure TA suggests diVerent mechanisms of dis- since the presence of any of these manifesta- ease in PMR and TA, supporting the view of tions generally implies significant pain and two separate conditions or one common functional impairment of the patient and are disease in which host susceptibility influences easily detectable on physical examination, it the clinical expression. Further studies in other seems likely most occurrences would have been populations are needed to confirm our results. reported in the medical records and therefore included in this study. Alternatively, this diVer- 1 O’DuVy JD, Wahner HW, Hunder GG. Joint imaging in ence may simply reflect the variability in mus- polymyalgia rheumatica. Mayo Clin Proc 1976;51:519–24. 2 Douglas WA, Martin BA, Morris JH. Polymyalgia

culoskeletal manifestations of PMR in diVerent rheumatica: an arthroscopic study of the shoulder joint. http://ard.bmj.com/ populations. In this sense, our findings are in Ann Rheum Dis 1983;42:311–6. 3 Salvarini C, Cantini F, Olivieri I, et al. Proximal in close agreement with Gran et al who also active polymyalgia rheumatica. Ann Intern Med 1997;127: observed a low frequency of distal pitting 27–31. 4 Salvarini C, Cantini F, Olivieri I, Hunder GG. Polymyalgia oedema (0.4%) in a recent prospective study rheumatica: a disorder of extraarticular synovial struc- conducted in Norway.10 The reason for this tures?. J Rheumatol 1999;26:517–21. 5 Salvarini C, Cantini F, Macchioni P, et al. Distal variability among diVerent populations may musculoskeletal manifestations in polymyalgia rheumatica. well be genetic. A prospective follow-up study. Arthritis Rheum 1998;41:

1221–6. on September 26, 2021 by guest. Protected copyright. As expected, PMR with proximal aching and 6 Healey LA. Long-Term follow-up of polymyalgia morning stiVness was the most frequent rheumatica: evidence for synovitis. Semin Arthritis Rheum 1984;13:322–8. musculoskeletal manifestation in patients with 7 Al-Hussaini AS, Swannell AJ. Peripheral joint involvement TA, occurring in 56% of cases. In addition to in polymyalgia rheumatica: a clinical study of 56 cases. Br J Rheumatol 1985;24:27–30. the frequent proximal symptoms, only 11% of 8 Salvarini C, Gabriel S, Hunder GG. Distal extremity swell- patients with TA developed distal peripheral ing with pitting edema in polymyalgia rheumatica. Report of nineteen cases. Arthritis Rheum 1996;39:73–80. arthritis. This percentage was lower than that 9 Salvarini C, Hunder GG. Musculoskeletal manifestations in reported in a population based study recently a population-based cohort of patients with arteri- 9 tis. Arthritis Rheum 1999;42:1259–66. conducted at the Mayo Clinic (23%). The 10 Gran JT, Myklebust G. The incidence and clinical clinical characteristics and distribution of characteristics of peripheral arthritis in polymyalgia rheu- matica and temporal arteritis: a prospective study of 231 peripheral joint inflammation observed in these cases. Rheumatology 2000;39:283–7. patients were similar to those described in the 11 Chuang TY, Hunder GG, Ilstrup DM, Kurland LT. Polymyalgia rheumatica. A 10 year epidemiologic and group with isolated PMR. With the exception clinical study. Ann Intern Med 1982;97:672–80. of the sternoclavicular joints, no erosive 12 Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification changes were seen. In comparing patients with of . Arthritis Rheum 1990;33:1122–8. musculoskeletal symptoms with those without, 13 Narváez J, Nolla-Solé JM, Clavaguera MT, Valverde-Garcia J, Roig-Escofet D. Long-term therapy in polymalgia we observed that the group with peripheral rheumatica: eVect of coexistent temporal arteritis. J Rheu- arthritis seemed to have more severe disease matol 1999;26:1949–52. 14 Omdal R, Husby G. Coexistence of temporal arteritis/ characterised by more laboratory abnormali- polymyalgia rheumatica and rheumatoid arthritis. Clin ties reflecting inflammation and increased inci- Rheumatol 1984;3:525–7. 15 Hall S, Ginsburg WW, Vollertsen RS, Hunder GG. The dence of constitutional symptoms, jaw claudi- coexistence of rheumatoid arthritis and giant cell arteritis. J cation, and visual problems. Interestingly, an Rheumatol 1983;10:995–7.

www.annrheumdis.com