Family Practice Advance Access published online on August 7, 2008
Family Practice, doi:10.1093/fampra/cmn044
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Polymyalgia rheumatica in primary care: a cohort study of the diagnostic criteria and outcome
a Hoyland House General Practice, Painswick, Glos
b Royal National Hospital for Rheumatic Diseases, Bath, Avon
c Research and Development Support Unit, Gloucestershire Hospital NHS Trust, Gloucester, Glos
d Department of Rheumatology, Southend University Hospital, Essex
e Department of General Practice, University of Aberdeen, Aberdeen
f Academic Unit of Primary Care, National School of Primary Care Research, University of Bristol, 25 Belgrave Road, Bristol BS8 2AA, UK
Received 19 November 2007; Revised 26 May 2008; Accepted 8 July 2008.
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Abstract |
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Background. Polymyalgia rheumatica (PMR) is common and is usually diagnosed and managed in primary care. There are no generally accepted primary care criteria for diagnosis.
Objectives. To identify what features are used to diagnose PMR, to benchmark these against diagnostic criteria and to identify features at diagnosis with prognostic significance.
Methods. This was a retrospective cohort study of all patients diagnosed with PMR in three UK general practices between January 1994 and December 2003. The medical records were examined for features of PMR. The duration of steroid treatment was used as a proxy for duration of disease. Analysis of prognostic predictors was by Cox proportional hazards models.
Results. One hundred and eighty-three patients were identified, giving an overall annual incidence of 11.3 per 10 000 patients aged 50 or over. The median age at diagnosis was 75 (interquartile range 69, 79) years: 138 (75%) were female. The most common diagnostic features were proximal muscle pain in 151 (82%), raised inflammatory markers in 160 (87%), clinical response to corticosteroids in 166 (91%) and normalization of inflammatory markers in 147 (81%). Twenty (11%) had normal inflammatory indices. The median duration of treatment was 1.4 years (interquartile range 0.8, 2.4). Female sex and raised inflammatory markers were independently associated with longer treatment: female hazard ratio 1.5 (1.0, 2.2) P = 0.047 and raised inflammatory markers 2.0 (1.2, 3.2) P = 0.01.
Conclusions. Primary care practitioners do not use established criteria to diagnose PMR and sometimes diagnose the condition even when inflammatory markers are normal. This exposes patients to a risk of inappropriate steroid use.
Keywords. Polymyalgia rhematica, diagnosis, primary healthcare.
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Introduction |
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Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease of elderly people characterized by proximal pain, stiffness, raised inflammatory markers and response to steroids.1 It has a major impact on quality of life, and is associated with high usage of primary and secondary health care.2,3 In addition to the direct impact of the disease, oral corticosteroid treatment is associated with adverse effects. Nearly one-quarter of UK patients on long-term steroids have PMR as the indication for treatment.4
Most patients are diagnosed and managed in primary care although there is a wide variation of practice.5 There is no gold standard diagnostic test although most patients have a raised erythrocyte sedimentation rate (ESR) or plasma viscocity.6,7 Various diagnostic algorithms have been formulated for research and clinical practice. However, the four main published criteria differ significantly in their emphasis and disease description.8–11 Thus, there are many pitfalls that may predispose the clinician to diagnostic error.2,12 The differential diagnosis for patients with pain, stiffness and raised inflammatory markers includes rheumatoid arthritis, malignancy and hypothyroidism; delays in diagnosis of these conditions may lead to poor outcomes. Patients with non-inflammatory musculoskeletal disease such as cervical spondylosis or degenerative shoulder disease may have symptoms that are suggestive of PMR. Incorrect diagnoses may cause adverse effects from unnecessary steroid treatment.
The reported annual incidence varies between 1.3 and 11.3 per 10 000 individuals aged over 50 years.11,13–15 Some of this variation may reflect different awareness of the condition in general practice or lack of uniform criteria used to make the diagnosis.16 The incidence in UK primary care has been estimated in an analysis of electronic records between 1990 and 2001. It increased from 6.9 to 9.3 per 10 000 aged over 40 years during this period.17 PMR is more commonly diagnosed in females, though this difference decreases with increasing age.
The prognosis of PMR is also uncertain. Secondary care studies indicate that the main predictor of relapse is a high initial ESR.18 Neither age nor sex appear to predict relapse.18 There have been no studies looking at prognostic factors in primary care.
We therefore performed a primary care study to examine the diagnostic criteria used for PMR and to examine features that predicted a poor outcome.
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Methods |
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This was a retrospective cohort study in three general practices in Gloucestershire, UK. The practice population in January 1998 (the midpoint of the study) totalled 37 908 patients, 16 102 being over 50 years of age. All the practices maintain fully computerized records. These were searched to identify all new diagnoses of PMR (identified by Read code N20, the highest code in the hierarchy, so identifying all subtypes of PMR) between January 1994 and December 2003. However, patients with a diagnosis of temporal arteritis alone (Read code G755) or temporal arteritis with associated PMR (Read code N200) at the time of diagnosis were excluded.
The records were examined (for a period of 2 years after diagnosis, and a short period before diagnosis) for features present in any of the criteria that make up the four case definitions.81–11 Values of ESR above 30 mm/hour were regarded as abnormal as were plasma viscosity values above 1.72 mPas and C-reactive protein values above 6 mg/l. Possible differential diagnoses (rheumatoid arthritis, internal malignancy or hypothyroidism) occurring within 2 years of the diagnosis of PMR were also identified.
Analysis
Simple descriptive statistics were used. For non-parametrically distributed variables, medians and interquartile ranges were used, with Mann–Whitney tests for significance. For analysis of possible predictors of a poor prognosis, Cox proportional hazards models were created. Variables significantly associated with a poorer prognosis with a univariable P-value of <0.1 were entered into a multivariable Cox model, but only those with a P-value <0.05 were retained in the final model. Analyses were performed using Stata, release 9.19
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Results |
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One hundred and eighty-three patients with PMR were identified from the computerized records, giving an overall annual incidence of 11.3 per 10 000 patients aged 50 or over. In the first 4 years, 9–15 patients were identified each year; this figure rose to 19–27 for all subsequent years. The median age at diagnosis was 75 (interquartile range 69, 79) and 138 (75%) were female. Only 29 (16%) were referred to secondary care for confirmation of diagnosis or management.
Diagnostic criteria recorded
The criteria that were recorded in the notes contributing to the diagnosis of PMR are shown in Table 1. Six patients had a record of depression and 11 a record of weight loss at the index presentation. Of the 183 patients, 20 (11%) had normal inflammatory indices at diagnosis and a further three (2%) apparently had no measurement of inflammatory markers. The most common features contributing to a diagnosis of PMR were a symptomatic response to a trial of oral corticosteroids (91%), raised inflammatory markers (90%), proximal muscle pain (82%) and normalization of inflammatory markers (81%). Early morning stiffness (a criterion common to all four published diagnostic criteria) was recorded in only 19% of cases. How far these diagnostic criteria fitted with the four published criteria is set out in Table 2. All these criteria require exclusion of alternative diagnoses. Although not recorded, we assumed this had been done for the purposes of matching patients against the criteria. Ten per cent or less of these patients met any of the published criteria.
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Outcome of the patients diagnosed and treated as PMR
Of the cohort of 183 patients, 130 (71%) had ceased steroid treatment, after a median of 1.4 years of treatment (interquartile range 0.8, 2.4). Patients had a median of 11 (7, 16) primary care consultations for PMR; 26 (14%) were referred to secondary care for their PMR, with a median of 3 (1, 5) consultations in that setting.
Only three variables were associated with a longer duration of treatment (as a proxy for prognosis) with a P-value <0.1. These were sex, with females having a longer duration of treatment—odds ratio 1.4 (95% confidence interval 0.96, 2.1, P = 0.08); the presence of symmetrical pain at diagnosis—odds ratio 1.4 (0.95, 2.0), P = 0.09 and having raised inflammatory markers—odds ratio 1.9 (1.1, 3.1), P = 0.01. In multivariable Cox analysis, both sex and raised inflammatory markers were independently associated with a longer duration of treatment: female sex odds ratio 1.5 (1.0, 2.2) P = 0.047 and raised inflammatory markers odds ratio 2.0 (1.2, 3.2) P = 0.01. Log–log diagnostic plots on the Cox models were essentially parallel, supporting the assumption that the hazard ratio was constant over time. The difference in duration of treatment between those with normal and those with raised inflammatory markers is illustrated by a Kaplan–Meier plot in Figure 1.
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Within 2 years of the diagnosis of PMR, nine patients developed rheumatoid arthritis, seven cancer and six hypothyroidism. Using published incidence figures, the expected numbers of new diagnoses over 2 years in 183 patients of this age are rheumatoid arthritis less than one,20 cancer nine21 and hypothyroidism also less than one.22 Diagnosis of an alternative condition was no more likely in patients with normal inflammatory markers compared with patients with raised markers. The median starting dose of prednisolone was 15 mg (interquartile range 15, 20). In 25 (14%), the starting dose of prednisolone was 25 mg or greater.
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Discussion |
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This observational study identified 183 patients newly diagnosed with PMR in a decade. Although all patients had one or more symptoms of the condition, and most had raised inflammatory markers, only a small proportion had features recorded in their medical records that fulfilled the criteria established for diagnosis. Most patients improved with steroids, and over 70% were able to stop medication, though generally after more than a year of treatment. Two alternative diagnoses—rheumatoid arthritis and hypothyroidism—were much more common than expected in the 2 years after diagnosis. The duration of treatment was shorter in those without raised inflammatory markers and was shorter in men than in women.
Strengths and weaknesses
There are clear limitations in interpreting this study. Because data were collected retrospectively (though from contemporary records), the study relies upon GPs’ recording. Some features, such as morning stiffness, that may have influenced diagnosis, may not have been recorded. This problem may have particularly affected the early years of the study, as computerized recording was less familiar to the GPs. Electronic records are particularly prone to omission of negative findings, though otherwise are deemed to be excellent.23 However, it is reasonable to infer that what was recorded were the clinical features considered by the GPs to be the most important diagnostically. Furthermore, the diagnosis was only confirmed by specialist opinion in 17% of the cases. It is certainly possible that a proportion of the diagnoses were incorrect. However, the mean age at diagnosis, incidence rate and duration of treatment are similar to those figures published in secondary care studies. Although this is the largest study of PMR in primary care, the possibility of false-positive or -negative findings remains: this could be addressed in a larger study using a national electronic database.
Diagnosis of PMR
There is very significant scope for error in making the diagnosis of PMR. Many other common conditions have clinical features in common with it. The consequences of a misdiagnosis in primary care may be long-term treatment with corticosteroids. One study showed that one-third of patients with PMR had had significant side effects from corticosteroid treatment by 2 years.24 As PMR is one of the commonest reasons for long-term corticosteroid treatment in primary care, diagnostic accuracy is particularly important.4,25 Surprisingly, those with normal inflammatory markers were no more likely to receive an alternative diagnosis in the following 2 years.
In this study, GPs recorded the presence of proximal muscle pain (82%), symmetrical distribution of the pain (61%), symptomatic response to a trial of steroids (91%) and normalization of inflammatory indices on steroids (81%) as the main features supporting the diagnosis of PMR. Doctors often accepted a relatively short duration of symptoms as acceptable for making the diagnosis, in that the duration of symptoms (where recorded) was less than 2 weeks in almost half of the cohort. This duration may be insufficient to exclude the possibility of post-viral myalgia or other self-limiting causes of muscular pain. The presence of morning stiffness was recorded in only 34 (19%), yet this is a feature that is frequently used by rheumatologists to discriminate between inflammatory causes of pain (such as PMR) and non-inflammatory causes (such as cervical spondylosis). Many rheumatologists would consider that it is unusual to have PMR if there is no morning stiffness. GPs may not be aware of this, and this clinical feature may improve diagnostic accuracy.
Doctors documented the response to steroids very well, suggesting they may have used steroid responsiveness as part of the diagnostic process. However, in 25 of the cases in which a steroid trial was specifically recorded, the dose of prednisolone was more than 20 mg daily. Two of the four published criteria use a response to a steroid trial as one of their criteria, but both specify a dose of less than or equal to 20 mg daily.9,10 The potential difficulty with using response to higher doses of prednisolone is that many conditions whose symptoms mimic PMR may respond symptomatically to higher doses of corticosteroids with normalization of indices of inflammation. The characteristic of PMR is responsiveness to low-dose corticosteroids. A further ambiguity is that the diagnostic criteria do not make it clear whether it is a symptomatic response to steroids, a biochemical response to steroids, or both, that should be used in judging the success of a steroid trial. However, recent consensus efforts to develop classification criteria for the polymyalgic syndrome agreed that the characteristic steroid response in PMR is greater than 70% patient global improvement within a week to prednisolone 15–20 mg daily with resolution of laboratory indices of inflammation within 3–4 weeks.26
In 20 (11%), the inflammatory indices were normal at diagnosis. This is well described in secondary care series.6 In one study of 70 patients with biopsy-proven temporal arteritis, 7% had normal ESRs at presentation and in another series from the Mayo clinic 22.5% of patients with giant cell arteritis had a normal ESR at diagnosis.14 Other studies have quoted rates of normal ESRs in patients with PMR of between 7% and 20%.27 How clinicians make the diagnosis in these circumstances, and whether non-specialists should make the diagnosis without a specialist opinion in these circumstances, remains undecided.
We believe that there is a need for clearly defined and workable diagnostic criteria for PMR in primary care. These should identify what is required for a generalist to make a diagnosis of PMR safely. They should thus have a high specificity, even if at the expense of a loss of sensitivity, and should indicate when specialist referral is advisable. For example, it may be considered that non-specialists should not make the diagnosis of PMR if the indices of inflammation are normal or if there is not a rapid and complete clinical or biochemical response to a therapeutic trial of low-dose corticosteroids. Clinicians should be encouraged to record a minimum data set in making the diagnosis so that later clinicians, who may see the patient some years after the initial diagnosis, can be confident the diagnosis was soundly made. Such a data set could be incorporated in guidelines.
Clinical predictors of outcome at diagnosis
Only two variables predicted duration of treatment, which we used as a proxy for duration of illness. Males and those with normal inflammatory indices at diagnosis had a better prognosis. A secondary care study of similar size to this one found that increased age at diagnosis and a higher ESR predicted relapse.26 One advantage this present study has is that it was population based and that possible selection bias caused by different referral patterns to secondary care should have been avoided.
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Conclusion |
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In this large study in UK primary care, 83% of the patients with a diagnosis of PMR were diagnosed and managed exclusively in primary care without reference to specialist opinion. GPs do not appear to have used any of the four published diagnostic criteria for PMR. We believe there is a pressing need to produce a clear and workable set of diagnostic guidelines for PMR and one addresses whether it is wise for a generalist to diagnose PMR in a patient with normal inflammatory indices. Such efforts are underway with the European League Against Rheumatism and the American College of Rheumatology sponsored international prospective study to develop classification criteria for the polymyalgic syndrome.26
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Declaration |
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Funding: Department of Health's NIHR School for Primary Care Research funding scheme to W.H.
Ethical approval: None.
Conflicts of interest: None.
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Acknowledgments |
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The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. There was no specific project funding.
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Notes |
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Barraclough K, Liddell WG, du Toit J, Foy C, Dasgupta B, Thomas M and Hamilton W. Polymyalgia rheumatica in primary care: a cohort study of the diagnostic criteria and outcome. Family Practice 2008; Pages 6: 1–6.
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